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WO2006056166A2 - Method for the addition of amides ureas lactams and carbamates to alkynes - Google Patents

Method for the addition of amides ureas lactams and carbamates to alkynes Download PDF

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WO2006056166A2
WO2006056166A2 PCT/DE2005/002048 DE2005002048W WO2006056166A2 WO 2006056166 A2 WO2006056166 A2 WO 2006056166A2 DE 2005002048 W DE2005002048 W DE 2005002048W WO 2006056166 A2 WO2006056166 A2 WO 2006056166A2
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heteroaryl
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WO2006056166A3 (en
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Lukas Goossen
Jan E. Rauhaus
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Studiengesellschaft Kohle gGmbH
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/02—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • C07C233/03—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having nitrogen atoms of carboxamide groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with carbon atoms of carboxamide groups bound to hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/08—Preparation of carboxylic acid amides from amides by reaction at nitrogen atoms of carboxamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/06—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D205/08—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with one oxygen atom directly attached in position 2, e.g. beta-lactams
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/36—Oxygen or sulfur atoms
    • C07D207/40—2,5-Pyrrolidine-diones
    • C07D207/404—2,5-Pyrrolidine-diones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. succinimide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D211/74—Oxygen atoms
    • C07D211/76—Oxygen atoms attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
    • C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D223/08—Oxygen atoms
    • C07D223/10—Oxygen atoms attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
    • C07D225/02—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/70—One oxygen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/18—Oxygen atoms
    • C07D263/20—Oxygen atoms attached in position 2
    • C07D263/22—Oxygen atoms attached in position 2 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms

Definitions

  • the invention relates to a process for the preparation of enamides, N-alkenylureas, N-alkenyllactams and N-alkenylcarbamates by reacting amides, ureas, lactams and carbamates with terminal alkynes in the presence of a transition metal catalyst.
  • enamides serve as versatile synthetic building blocks, for example, as a source of enantiomerically pure amides, amines, and amino acids as well as for the preparation of heterocycles (Scheme 1). Easy access to this class of compounds is therefore of great interest.
  • a BASF patent describes a process for preparing N-vinyl compounds by addition of nitrogen nucleophiles to acetylene, in which ruthenium (III) and osmium (III) salts are used as catalysts.
  • this process is strictly limited to the known highly reactive acetylene with respect to the alkyne component, unsuitable for other alkynes, and requires high temperatures and pressures.
  • the object of the present invention was to develop a generally applicable, mild process for the preparation of enamides, N-alkenylureas, N-alkenyllactams and N-alkenylcarbamates.
  • the particular difficulty was that the known catalysts for the addition of nucleophiles to alkynes such.
  • ruthenium (III) halides, Ru 3 CO 12 or ruthenium (II) arene compounds showed no activity for the desired reaction. Therefore, the catalysts had to be redeveloped, a systematic optimization of an existing catalyst system was not possible.
  • This method differs from the method of Watanabe et al. in particular by the catalyst used which is not prepared from Ru 3 CO 12 but from ruthenium compounds with carbon-containing ligands selected from the group alkyl, aryl, vinyl, benzyl, allyl, dienyl, olefin, diene, arene.
  • the substituents R 2 and R 3 are independently selectable from the series heteroatoms from the series H, S, Si, N, O, Cl, Br, I, B, linear and branched C 1 - C 10 alkyl or C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 - vinyl or heteroaryl selected from pyridine, pyrimidin, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan , linear and branched C 1 -C 10 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear and branched C 1 - C 10 alkyl or halogenated C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - C 10
  • the fragment X is an atom from the series C, S, P and can itself further substituents from the series linear and branched C 1 - Qo-alkyl or C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 - alkyloxy or C 1 - C 10 aryloxy, halogenated linear and branched C 1 - Qo alkyl, or halogenated C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - C 10 - arylaminocarbonyl , linear and branched C 1 - C 10 acyl, linear and branched C 1 - C 1 acyl, linear and branched C 1 - C 1
  • the substituent R 1 of the terminal alkyne is selectable from the series consisting of heteroatoms from the series S, Si, N, O, Cl, Br, I, B, linear and branched C 1 -C 10 -alkyl or C 1 -C 10 -aryl, vinyl or heteroaryl from the series pyridine, pyrimidine, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan, linear and branched C 1 - alkyloxy or C 1 - Qo-aryloxy, halogenated linear and branched C 1 - C 10 - alkyl, or halogenated C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1
  • the catalysts used are ruthenium organyl complexes, preferably ruthenium (II) organyl complexes, particularly preferably bis (organyl) ruthenium (II) complexes, and very particularly preferably bis (2-methylallyl) ruthenium (II) complexes.
  • the ruthenium is optionally stabilized by further ligands from the series amines, phosphines, N-heterocyclic carbenes, nitriles, olefins.
  • Phosphines are preferably used as ligands, particularly preferably phosphines are used in combination with amines, very particularly preferably a combination of electron-rich pyridines and trialkylphosphines is used as ligands. Alternatively, two or more of these ligands may also be combined in a molecule to form a chelating ligand.
  • a catalyst amount of from 0.001 mol% to 20 mol%, based on the nitrogen derivative, is used.
  • a catalyst amount of 0.01 mol% to 3 mol% is used.
  • the inventive method is carried out at temperatures of -20 ° C to 200 ° C, preferably at 50 ° C to 200 ° C and more preferably at 80 ° C to 120 ° C.
  • the process according to the invention can be carried out in the presence of a solvent or in bulk.
  • solvents of one of the starting materials pentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylenes, ethylbenzene, mesitylene, dioxane, tetrahydrofuran, diethyl ether, dibutyl ether, methyl t-butyl ether, diisopropyl ether, diethylene glycol dimethyl ether, methanol, Ethanol, propanol, isopropanol, methyl acetate, ethyl acetate, t-butyl acetate, dimethylformamide, diethylformamide, N-methylpyrrolidone, dimethylacetamide, dimethylsulfoxide, sulfolane, acetonitrile, propylene carbonate,
  • Aromatic hydrocarbons, amides, esters and ethers are preferably used.
  • the process according to the invention is preferably carried out in such a way that the solids are initially introduced and the liquid starting materials and the solvent are metered in.
  • the reaction mixture is preferably worked up by distillation and / or by extraction or crystallization after completion of the reaction.
  • Reaction conditions 0.50 mmol pyrrolidin-2-one, 1.00 mmol 1-hexyne, 0.01 mmol Ru source, 0.06 mmol ligand, toluene, 100 0 C, 15 h; a) GC yields with n-tetradecane as internal standard; b) diastereomer ratio according to GC;
  • the compound was prepared analogously to compound 3.2 of azetidin-2-one (1.3) (71.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way 3.3 (104 mg, 70% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.3: 4.3 was 2: 1.
  • the compound was prepared analogously to compound 3.2 from pipridin-2-one (1.4) (99.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.4 (165 mg, 70% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.4: 4.4 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from azepan-2-one (1.5) (113.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.5 (179 mg, 94% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.5: 4.5 was 30: 1.
  • Example 21 N - ((E) -hex-1-enyl) -azonane-2-one (3.6)
  • the compound was prepared analogously to compound 3.2 from azonan-2-one (1.6) (141.2 mg, 1.0 mmol) and 1-hexine (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / Ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.6 (186 mg, 86% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.6: 4.6 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from N-phenylacetamide (1.7) (135.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way, 3.7 (196 mg, 90% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.7: 4.7 was 30: 1
  • the compound was prepared analogously to compound 3.2 from N-methylbenzamide (1.8) (135.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, Gradient elution: 100/0 to 20/80)). In this way, 3.8 (98 mg, 46% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.8: 4.8 was 16: 1.
  • Example 24 ⁇ N- (4-Acetyl-phenyl) - ⁇ - ((E) -hex-1-enyl) -acetamide (3.9)
  • the compound was analogous to compound 3.2 from N- (4-acetyl-phenyl) -acetamide (1.9) (177.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). cleaned. In this way, 3.9 (84 mg, 33% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.9: 4.9 was 30: 1.
  • Example 25 N- (4-Ethoxy-phenyl) -N - ((E) -hex-1-enyl) -acetamide (3.10)
  • the compound was prepared analogously to compound 3.2 from N-methylformamide (1.12) (59.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way, 3.12 (110 mg, 83% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.12: 4.12 was 30: 1, rotamer ratio 3: 1.
  • the compound was prepared analogously to compound 3.2 from N-methylacetamide (1.13) (73.1 mg, 1.0 mmol) and 1 -hexine (B1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.13 (126 mg, 84% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.13: 4.13 was 30: 1, rotamer ratio 2: 1.
  • Example 27 ⁇ N - ((E) -Hex-1-enyl) ⁇ N- (isopropyl) acrylamide (3.14)
  • the compound was prepared analogously to compound 3.2 from N-rlsopropylacrylamide (1.14) (113.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.14 (74 mg, 38% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.14: 4.14 was 30: 1.
  • Example 28 1,4-Di - ((E) -hex-1-enyl) piperazine-2,5-dione (3.15)
  • the compound was prepared analogously to compound 3.2 from piperidine-2,5-dione (1.15) (114.1 mg, 1.0 mmol) and 1-hexyne (2.1) (458 ⁇ L, 4.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.15 (259.1 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.15: 4.15 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from imidazolidin-2-one (1.16).
  • Example 30 (4S, 5K) - ⁇ - ((E) -hex-enyl) -3,4- (dimethyl) -5-phenyl) imidazolidin-2-one
  • the compound was prepared analogously to compound 3.2 from I, 5 (S) -dimethyl-4 (R) -phenyl-imidazolidin-2-one (1.17) (190.3 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.17 (262 mg, 99% of theory) was used as colorless solid.
  • the diastereomer ratio (E: Z) 3.17: 4.17 was 23: 1.
  • Example 31 (2S) -N - ((E) -hex-enyl) -5- (oxo-pyrrolidine) -2-carboxylic acid methyl ester
  • the compound was prepared analogously to compound 3.2 from 5-oxopyrrolidin-2 (p ) - Carboxylic acid methyl ester (1.18) (143.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20 / 80). In this way, 3.18 (210.3 mg, 96% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.18: 4.18 was 6: 1.
  • the compound was prepared analogously to compound 3.2 from oxalidin-2-one (1.19) (87.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.19 (147.9 mg, 90.1% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.19: 4.19 was 23: 1.
  • Example 33 (4S) -3 - ((E) -hex-1-enyl) -4- (isopropyl) -oxazo-din-2-one (3.20)
  • Compound became analogous to compound 3.2 from 4 (S) -isopropyl-oxalidine 2-one (1.20) (129.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.20 (198.9 mg, 97% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.20: 4.20 was 30: 1.
  • Example 34 (4R, 5S) -3 - ((E) -hex-1-enyl) -5- (methyl) -4- (phenyl) oxazolidin-2-one (3.21)
  • the compound was analogous to compound 3.2 5 (S) -methyl-4 (R) -phenyl-oxalidin-2-one (1.21) (177.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 ⁇ L, 2.0 mmol) and by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.21 (211.1 mg, 84% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.21: 4.21 was 21: 1.
  • the compound was prepared analogously to compound 3.2 from pyrrolidine-2,5-dione (1.22) (99.1 mg, 1.0 mmol) and hexine (2.1) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way 4.22 (22 mg, 12% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.22: 4.22 was 1: 2 (according to GC). After column chromatography, only the Z-diastereomer was obtained.
  • Example 36 (2 ⁇ ) -3- (2-Oxopyrrolidin-1-yl) -propenoic acid methyl ester (3.23)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and methyl acrylate (2.2 ) (178 ⁇ L, 2.0 mmol) and purified by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.23 (211.1 mg, 84% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.23: 4.23 was 30: 1.
  • Example 37 ⁇ N - ((E) -3-Methoxy-prop-1-enyl) -pyrrolidin-2-one (3.24)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and 3-methoxy-propyne (2.3) (169 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to • 20/80). In this way 3.24 (145 mg, 93% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.24: 4.24 was 8: 1.
  • Example 38 ⁇ N - (( ⁇ ) -3,3-Dimethylbut-1-enyl) pyrrolidin-2-one (3.26)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L , 1.0 mmol) and 3,3-dimethyl-but-1-one (2.5) (246 ⁇ L, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20 / 80). In this way 3.26 (161.8 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.26: 4.26 was 30: 1. -. ..
  • Example 39 N - ((E) -3-Methyl-1,3-di-1-enyl) pyrrolidin-2-one (3.27)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and 2-methyl-but-1-en-3-yn (2.6) (190 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, Gradierite elution: 100/0 until 20/80). In this way 3.27 (141.2 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.27: 4.27 was 24: 1. ,
  • Example 40 T $ - ((E) -2-trimethylsylvinyl) pyrrolidin-2-one (3.28)
  • the compound was prepared analogously to compound 3.1 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and ethynyl-trimethylsilane (2.7) (277 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.28 (120.0 mg, 70% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.28: 4.28 was 3: 1.
  • Example 41 ' N- ( ⁇ ) -2-phenyl-vinylpyrrolidin-2-one (3.29)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and phenylacetyene (2.8) (220 ⁇ L, 2.0 mmol) and by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.29 (180.0 mg, 99% of theory) was obtained as a grayish solid.
  • the diastereomer ratio (E: Z) 3.29: 4.29 was 22: 1.
  • Example 42 N - ((E) -4-Phenyl-but-1-enyl) pyrrolidin-2-one (3.30)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol and but-3-ynilbenzene (2.9) (281 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.30 (201.6 mg, 99% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.30: 4.30 was 30: 1.
  • Example 43 Yl - ((Z) -4-Phenyl-but-1-enyl) pyrrolidin-2-one (4.30)
  • the compound was prepared analogously to compound 4.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol and but-3-yn-benzene (2.9) (281 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 4.30 (198 mg, 92% of theory) was obtained as a colorless solid.
  • the diastereomer ratio (E: Z) 3.30: 4.30 was 1: 8.
  • Example 44 1 $ - ((E) -dodeca-1,1-dienyl) pyrrolidin-2-one (3.31)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol). and dodec-1-en-II-in (2.10) (463 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.31 (241.1 mg, 99% of theory) was obtained as a yellowish oil.
  • the diastereomer ratio (E: Z) 3.31: 4.31 was 30: 1.
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and hept-l-en-6-yn (2.11) (188.3 mg, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.23 (170.3 mg, 95% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.32: 4.32 was 30: 1.
  • Example 46 N - ((E) -5-chloropent-1-enyl) pyrrolidin-2-one (3.33)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol and 5-chloro-pent-l-in (2.12) (212 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.33 (148 mg, 80% of theory) was obtained as a colorless oil.
  • the diastereomer ratio (E: Z) 3.33: 3.43 was 30: 1.
  • Example 47 (2Z) -2- (2-oxopyrrolidin-1-yl) -3-phenylacrylic acid methyl ester (3.34)
  • the compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 ⁇ L, 1.0 mmol) and phenyl ethyl propionate (2.13) (229 ⁇ L, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.34 (154 mg, 63% of theory) was obtained as a yellowish solid.
  • the isomer ratio between the above-described compound and the other 3 isomers was 30: 1.

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Abstract

A method for the production of N-alkenyl compounds is disclosed, in which N-H compounds are reacted with terminal alkynes in the presence of catalytic amounts of organoruthenium complexes.

Description

Verfahren zur Addition von Amiden, Harnstoffen. Lactamen und Carbamaten an Alkine Process for the addition of amides, ureas. Lactams and carbamates on alkynes

Die Erfindung betrifft ein Verfahren zur Herstellung von Enamiden, N- Alkenylharnstoffen, N-Alkenyllactamen und N-Alkenylcarbamaten durch Umsetzung von Amiden, Harnstoffen, Lactamen und Carbamaten mit terminale Alkinen in Gegenwart eines Übergangsmetallkatalysators.The invention relates to a process for the preparation of enamides, N-alkenylureas, N-alkenyllactams and N-alkenylcarbamates by reacting amides, ureas, lactams and carbamates with terminal alkynes in the presence of a transition metal catalyst.

Eine Vielzahl von Naturstoffen sowie künstlich hergestellter Arzneistoffe z. B. mit sedativer, cytotoxischer oder entzündungshemmender Wirkung enthalten in ihrem Pharmakophor das Strukturelement eines Enamids. Enamide dienen weiterhin als vielseitige Synthesebausteine z.B. als Quelle für enatiomerenreine Amide, Amine und Aminosäuren sowie zur Darstellung von Heterocyclen (Schema 1). Ein einfacher Zugang zu dieser Verbindungsklasse ist daher von hohem Interesse. A variety of natural products and artificially produced drugs z. B. with sedative, cytotoxic or anti-inflammatory effect contain in their pharmacophore the structural element of an enamide. Furthermore, enamides serve as versatile synthetic building blocks, for example, as a source of enantiomerically pure amides, amines, and amino acids as well as for the preparation of heterocycles (Scheme 1). Easy access to this class of compounds is therefore of great interest.

Figure imgf000003_0001
Figure imgf000003_0001

Schema 11. Enamide in der Synthese:Scheme 11. Enamides in the synthesis:

1. Povarov-Reaktion, Lewissäure katalysierte [4+2]-Cycloaddition zwischen aromatischem Amin und elektronenreichen Alken (nur ein Diastereomer abgebildet)1. Povarov reaction, Lewis acid catalyzed [4 + 2] cycloaddition between aromatic amine and electron-rich alkene (only one diastereomer shown)

2. Iodierung mit iV-Iodsuccinimid2. Iodination with iV-iodosuccinimide

3. Palladium katalysierte Suzuki-Reaktion3. Palladium catalyzed Suzuki reaction

4. Cu katalysierte, enantioselektive Addition von Enamiden an Imine4. Cu-catalyzed, enantioselective addition of enamides to imines

5. Asymmetrische Hydrierung von Dehydroaminosäuren und Enamiden nach Reetz, de Vries, Feringa und Bruneau5. Asymmetric hydrogenation of dehydroamino acids and enamides according to Reetz, de Vries, Feringa and Bruneau

6. Palladium katalysierte Heck-Oleflnierung6. Palladium catalyzed Heck olefination

7. Eu(fod)3 katalysierte [4+2]-Heterocycloaddition (nur ein Diastereomer abgebildet) Zur Synthese dieser Verbindungen werden im Wesentlichen die folgenden Synthesen verwendet (Schema3):7. Eu (fod) 3 catalyzed [4 + 2] heterocycloaddition (only one diastereomer shown) For the synthesis of these compounds essentially the following syntheses are used (Scheme 3):

1. Ausgehend von syn- bzw. anti-α-TMS-ß-Aminoalkoholen und Säurechloriden können in einer Eintopfreaktion stereoselektiv 2s-bzw. Z- Enamiden generiert werden.1. Based on syn or anti-α-TMS-ß-amino alcohols and acid chlorides can stereoselectively 2s-or in a one-pot reaction. Z-enamides are generated.

2. Die palladiumkatalysierte Atnidierung von Enoltriflaten (1.4 eq. CsCO3, 3 mol % Pd2(dba)3) liefert ebenfalls Enamide, ist aber auch mit Sulfonamiden und Carbamaten durchführbar.2. The palladium-catalyzed oxidation of enol triflates (1.4 eq CsCO 3 , 3 mol% Pd 2 (dba) 3 ) also gives enamides but is also feasible with sulfonamides and carbamates.

3. Durch Palladium katalysierten Vinyltransfer von Vinylethern auf Stickstoff- Nucleophile (10 eq. Butylvinylether, 5 mol % (DPP)Pd(OCOCF3)2) entstehen Enamide, und als Koppelprodukt fallt Butylalkohol an.3. Palladium-catalyzed vinyl transfer of vinyl ethers to nitrogen nucleophiles (10 eq of butylvinyl ether, 5 mol% of (DPP) Pd (OCOCF 3 ) 2 ) gives rise to enamides, and the by-product is butyl alcohol.

Nachteilig bei diesen Verfahren sind insbesondere die begrenzte Verfügbarkeit der Einsatzstoffe, ihre Empfindlichkeit und ihr hoher Preis.Disadvantages of these processes are, in particular, the limited availability of the starting materials, their sensitivity and their high price.

4. Umsetzung von Hydroxylaminen mit Eisenpulver in einer Mischung von Essigsäureanhydrid und Essigsäure fuhrt zu den korrespondierenden iV-Acyl- Enamiden.4. Reaction of hydroxylamines with iron powder in a mixture of acetic anhydride and acetic acid leads to the corresponding iV-acyl-enamides.

Diese Reaktion ist hinsichtlich ihrer Anwendungsbreite beschränkt und liefert die Produkte nur als is/Z-Gemische.This reaction is limited in scope and provides the products only as is / Z mixtures.

5. Die CuI/NjN-Dimethylglycin katalysierte Kupplung von Vinylhalogeniden mit Amiden und Carbamaten in Gegenwart von 2 Äquivalenten CsCO3 liefert Enamide bzw. Alkenylcarbamate.1 5. The CuI / NjN-dimethylglycine catalyzed coupling of vinyl halides with amides and carbamates in the presence of 2 equivalents of CsCO 3 yields enamides or alkenyl carbamates. 1

Nachteilig sind hierbei insbesondere der hohe Preis des CsCO3, die Toxizität des Kupfers und die große Abfallmenge. 6. Eine klassische Darstellungsweise ist schließlich die Kondensationsreaktion von Aldehyden und Amiden in Gegenwart katalytischer Mengen an para- Toluolsulfonsäure (E/Z-Gemische).Disadvantages here are in particular the high price of the CsCO 3 , the toxicity of the copper and the large amount of waste. 6. Finally, a classical method of representation is the condensation reaction of aldehydes and amides in the presence of catalytic amounts of para-toluenesulfonic acid (E / Z mixtures).

Nachteilig sind hier die stark sauren Bedingungen und die hohen Temperaturen, die eine Anwendung dieser Reaktion auf unempfindliche Derivate beschränken.Disadvantages here are the strongly acidic conditions and the high temperatures which limit the application of this reaction to insensitive derivatives.

Figure imgf000005_0001
anU
Figure imgf000005_0001
ANU

Schema 12. Verschiedene Synthesen von EnαmidenScheme 12. Various syntheses of enαmides

Es bestand daher Bedarf an einem Verfahren, mit dem Enamide und artverwandte Substrate wie N-Alkenylharnstoffe, N-Alkenyllactame oder N-Alkenylcarbamate aus möglichst einfach verfügbaren und einfach handhabbaren Startmaterialien unter Vermeidung von Salzabfällen unter milden Bedingungen erzeugt werden können.There was therefore a need for a process by means of which enamides and related substrates such as N-alkenylureas, N-alkenyllactams or N-alkenylcarbamates can be produced from readily available and easily handled starting materials while avoiding salt wastes under mild conditions.

Amiden, Harnstoffen, Lactamen und Carbamaten sind vielfältig verfügbar und stellen daher ideale Startmaterialien dar. Die potentiell eleganteste Methode zur Darstellung von Enamiden und artverwandter Verbindungen, wäre eine Addition dieser Substrate an Alkine. Die unkatalysierte Variante dieser Umsetzung erfordert allerdings hohe Temperaturen und den Zusatz stöchiometrischer Mengen starker Basen, die die Anwendung dieser Reaktion auf empfindliche Derivate ausschließen. Während verschiedene katalytische Verfahren zur Addition reaktiver Nucleophile, wie Wasser, Carbonsäuren oder Amine an Alkine bekannt sind, gibt es nur zwei Beispiele für die Addition der reaktionsträgen Amiden an Alkine:Amides, ureas, lactams and carbamates are widely available and therefore ideal starting materials. The potentially most elegant method for the preparation of enamides and related compounds would be the addition of these substrates to alkynes. However, the uncatalyzed variant of this reaction requires high temperatures and the addition of stoichiometric amounts of strong bases which preclude the application of this reaction to sensitive derivatives. While various catalytic processes for the addition of reactive nucleophiles, such as water, carboxylic acids, or amines to alkynes, are known, there are only two examples of addition of the inert amides to alkynes:

In einem Artikel aus dem Jahre 1995 "Ruthenium Complex-catalyzed Addition ofN- Aryl substituted Amides to Alkynes " stellten Watanabe et a/. Untersuchungen zur katalytischen Hydroamidierung terminaler Alkine vor. Dabei erwiesen sich Trirutheniumdodecacarbonyl / Phosphin Gemische als wirksamste Katalysatoren.In a 1995 article "Ruthenium Complex Catalyzed Addition of N-Aryl Substituted Amides to Alkynes", Watanabe et al. Studies on the catalytic hydroamidation of terminal alkynes. Triruthenium dodecacarbonyl / phosphine mixtures proved to be the most effective catalysts.

Figure imgf000006_0001
Figure imgf000006_0001

Schema 14. Synthese N-Aryl-substituierter EnamideScheme 14. Synthesis of N-aryl-substituted enamides

Die Durchführung dieser Reaktion erfolgte unter Argonatmosphäre bei einer extrem hohen Temperatur von 180°C unter Druck in einem Stahl- Autoklaven. Das Substratspektrum der Reaktion ist sehr gering. So ist ein Arylsubstituent am Stickstoff essentiell für eine erfolgreiche Umsetzung, N-Alkyl-substituierte Formamide liefern „intractable mixtures". Die für diese Reaktion benötigten hohen Temperaturen und Drücke und das extrem begrenzte Substratspektrum lassen ihren Einsatz in der organischen Synthese wenig sinnvoll erscheinen.This reaction was carried out under argon atmosphere at an extremely high temperature of 180 ° C under pressure in a steel autoclave. The substrate spectrum of the reaction is very low. Thus, an aryl substituent on nitrogen is essential for successful conversion, N-alkyl-substituted formamides provide "intractable mixtures." The high temperatures and pressures required for this reaction and the extremely limited substrate spectrum make their use in organic synthesis seem less meaningful.

Weiterhin wird in einem Patent der BASF ein Verfahren zur Herstellung von N- Vinylverbindungen durch Addition von Stickstoffhucleophilen an Acetylen beschrieben, bei dem Ruthenium(III) und Osmium(III) Salze als Katalysatoren eingesetzt werden. Dieses Verfahren ist jedoch hinsichtlich der Alkinkomponente streng auf das bekanntermaßen hochreaktive Acetylen beschränkt, für andere Alkine ungeeignet und erfordert hohe Temperaturen und Drücke. H ^- H Kat ,R1Furthermore, a BASF patent describes a process for preparing N-vinyl compounds by addition of nitrogen nucleophiles to acetylene, in which ruthenium (III) and osmium (III) salts are used as catalysts. However, this process is strictly limited to the known highly reactive acetylene with respect to the alkyne component, unsuitable for other alkynes, and requires high temperatures and pressures. H ^ - H Kat, R 1

H-N NH-N N

R2 R 2

R2 HR 2 H

Die Aufgabe der vorliegenden Erfindung war es, ein allgemein anwendbares, mildes Verfahren zur Darstellung von Enamiden, N-Alkenylharnstoffen, N-Alkenyllactamen und N-Alkenylcarbamaten zu entwickeln. Die besondere Schwierigkeit bestand darin, dass die bekannten Katalysatoren für die Addition von Nucleophile an Alkine wie z. B. Ruthenium(III)halogenide, Ru3CO12 oder Ruthenium(II)arenverbindungen keine Aktivität für die gewünschte Umsetzung zeigten. Die Katalysatoren mussten daher neu entwickelt werden, eine systematische Optimierung eines bestehenden Katalysatorsystems war nicht möglich.The object of the present invention was to develop a generally applicable, mild process for the preparation of enamides, N-alkenylureas, N-alkenyllactams and N-alkenylcarbamates. The particular difficulty was that the known catalysts for the addition of nucleophiles to alkynes such. As ruthenium (III) halides, Ru 3 CO 12 or ruthenium (II) arene compounds showed no activity for the desired reaction. Therefore, the catalysts had to be redeveloped, a systematic optimization of an existing catalyst system was not possible.

Überraschenderweise wurde ein hocheffizientes und breit anwendbares Verfahren zur Addition von Stickstoffhucleophilen an Alkine gefunden welches dadurch gekennzeichnet ist, dass die Umsetzung in Gegenwart spezieller Rutheniumorganylkomplexen durchgeführt wird (Schema 2).Surprisingly, a highly efficient and widely applicable process for the addition of nitrogen nucleophiles to alkynes has been found, which is characterized in that the reaction is carried out in the presence of specific ruthenium organyl complexes (Scheme 2).

*—- . • JH R3 ^t Jf )=° * Ri /-NV O * R, v=/ W "b"* -. • JH R 3 ^ t Jf) = ° * Ri / - N VO * R, v = / W "b"

R1 (E) (Z) R 1 (E) (Z)

1 2 3 4 51 2 3 4 5

Schema 2. Erfindungsgemäße Addition von Stickstoffhucleophilen an terminale AlkineScheme 2. Addition of Nitrogen Nucleophiles to Terminal Alkynes According to the Invention

Vorteilhaft gegenüber den obengenannten traditionellen Verfahren ist, dass keine stöchiometrischen Zusätze, wie z. B. Basen benötigt werden und keine stöchiometrischen Mengen an Koppelprodukten anfallen, deren Abtrennung und Entsorgung in vielen Prozessen hohe Kosten verursachen. Die Vorteile des neuen Verfahrens gegenüber dem von Watanabe sind die weitaus größere Substratbreite, die niedrigen Temperaturen, das Arbeiten bei Atmosphärendruck, die exzellenten Ausbeuten und die hohen Regioselektivitäten.An advantage over the above traditional methods is that no stoichiometric additives such. As bases are required and do not accumulate stoichiometric amounts of by-products, their separation and disposal in many processes cause high costs. The advantages of the new Compared to Watanabe, the process involves far greater substrate width, lower temperatures, atmospheric pressure, excellent yields, and high regioselectivities.

Dieses Verfahren unterscheidet sich von dem Verfahren von Watanabe et a/. insbesondere durch den verwendeten Katalysator, der nicht aus Ru3CO12 sondern aus Rutheniumverbindungen mit kohlenstoffhaltigen Liganden aus der Reihe Alkyl, Aryl, Vinyl, Benzyl, Allyl, Dienyl, Olefin, Dien, Aren hergestellt wird.This method differs from the method of Watanabe et al. in particular by the catalyst used which is not prepared from Ru 3 CO 12 but from ruthenium compounds with carbon-containing ligands selected from the group alkyl, aryl, vinyl, benzyl, allyl, dienyl, olefin, diene, arene.

Im Unterschied zum Verfahren der BASF (EP 646571 Al) werden nicht Acetylen (Rl = H) sondern terminale Alkine (Rl o H) als Substrate eingesetzt, so dass keine N-Vinylverbindungen sondern N-Alkenylverbindungen erzeugt werden. Die in den Beispielen der Offenlegungsschrift genannten Katalysatoren (RuCl3, OsCl3, Ru(acac)3) sind zudem für die hier beschriebene Umsetzung ungeeignet.In contrast to the process of BASF (EP 646571 Al) not acetylene (Rl = H) but terminal alkynes (Rl o H) are used as substrates, so that no N-vinyl compounds but N-alkenyl compounds are produced. The catalysts mentioned in the examples of the disclosure (RuCl 3 , OsCl 3 , Ru (acac) 3 ) are also unsuitable for the reaction described here.

Im erfindungsgemäßen Verfahren werden Stickstoffhucleophile der allgemeinen Formel x eingesetzt.In the process according to the invention, nitrogen nucleophiles of the general formula x are used.

Figure imgf000008_0001
Figure imgf000008_0001

Formel xFormula x

Die Substituenten R2 und R3 sind dabei unabhängig voneinander wählbar aus der Reihe Heteroatome aus der Reihe H, S, Si, N, O, Cl, Br, I, B, lineare und verzweigte C1 - C10-Alkyl oder C1- Qo-Aryl oder Heteroaryl, lineare und verzweigte C1 - C10- Vinyl- oder Heteroaryl aus der Reihe Pyridin, Pyrirnidin, Pyridazin, Pyrazin, Triazin, Tetrazin, Pyrrol, Pyrazol, Isoxazol, Imidazol, Oxazol, Thiazol, Thiophen, Furan, lineare und verzweigte C1 - C10-Alkyloxy oder C1 - C10-Aryloxy, halogenierte lineare und verzweigte C1 - C10-Alkyl oder halogenierte C1 - C10-Aryl oder Heteroaryl, lineare und verzweigte C1 - C10 Alkyl- oder C1 - C10-Arylaminocarbonyl, lineare und verzweigte C1 - C10 Acyl, lineare und verzweigte C1 - C10 -Dialkylamino, C1 - C10 Arylamino oder sind gemeinsam Bestandteil einer cyclischen C1 - C10- gesättigten oder ungesättigten Alkyl-, Aryl-, oder Heteroaryleinheit und können ihrerseits weitere Substituenten aus der Reihe lineare und verzweigte C1 - C10- Alkyl oder C1- C1O-AIyI oder Heteroaryl, lineare und verzweigte C1 - C10-Alkyloxy oder C1 - do-Aryloxy, halogenierte lineare und verzweigte C1 - C10-Alkyl oder halogenierte C1 — Cto-Aryl oder Heteroaryl, lineare und verzweigte C1 - C10 Alkyl- oder C1 - C10- Arylaminocarbonyl, lineare und verzweigte C1 — C10 Acyl, lineare und verzweigte C1 The substituents R 2 and R 3 are independently selectable from the series heteroatoms from the series H, S, Si, N, O, Cl, Br, I, B, linear and branched C 1 - C 10 alkyl or C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 - vinyl or heteroaryl selected from pyridine, pyrimidin, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan , linear and branched C 1 -C 10 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear and branched C 1 - C 10 alkyl or halogenated C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - C 10 arylaminocarbonyl, linear and branched C 1 - C 10 acyl, linear and branched C 1 - C 10 dialkylamino, C 1 - C 10 arylamino or are together part of a cyclic C 1 - linear saturated or unsaturated alkyl, aryl, or heteroaryl and may in turn bear further substituents from the series, and - C 10 branched C 1 - C 10 - alkyl or C 1 - C 10 alkyloxy or C 1 - - do-aryloxy, halogenated linear and branched C 1 - C 1O -AIyI or heteroaryl, and branched C 1 C 10 linear alkyl or halogenated C 1 -C t o-aryl or heteroaryl, linear and branched C 1 -C 10 alkyl or C 1 -C 10 arylaminocarbonyl, linear and branched C 1 -C 10 acyl, linear and branched C 1

— C10 Dialkylamino, C1 — C10 Arylamino, C1 — C10 Diarylarnino, Formyl, Oxo, Thio, Hydroxy, Carboxyl, Nitro, Cyano, Nitroso, und Halogene wie F, Cl, Br und I tragen.- C 10 dialkylamino, C 1 - C 10 arylamino, C 1 - C 10 diarylarnino, formyl, oxo, thio, hydroxy, carboxyl, nitro, cyano, nitroso, and halogens such as F, Cl, Br and I.

Das Fragment X ist ein Atom aus der Reihe C, S, P und kann seinerseits weitere Substituenten aus der Reihe lineare und verzweigte C1 — Qo-Alkyl oder C1- Qo-Aryl oder Heteroaryl, lineare und verzweigte C1 - C10-Alkyloxy oder C1 - C10-Aryloxy, halogenierte lineare und verzweigte C1 - Qo-Alkyl oder halogenierte C1 - C10-Aryl oder Heteroaryl, lineare und verzweigte C1 - C10 Alkyl- oder C1 - C10- Arylaminocarbonyl, lineare und verzweigte C1 — C10 Acyl, lineare und verzweigte C1 The fragment X is an atom from the series C, S, P and can itself further substituents from the series linear and branched C 1 - Qo-alkyl or C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 - alkyloxy or C 1 - C 10 aryloxy, halogenated linear and branched C 1 - Qo alkyl, or halogenated C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - C 10 - arylaminocarbonyl , linear and branched C 1 - C 10 acyl, linear and branched C 1

- C1O Dialkylamino, C1 - C10 Arylamino, C1 - C10 Oxo, Thio, Hydroxy, Carboxyl und Halogene wie F, Cl, Br und I tragen.- C 1O dialkylamino, C 1 - C 10 arylamino, C 1 - C 10 oxo, thio, hydroxy, carboxyl and halogens such as F, Cl, Br and I.

R1 — HR 1 - H

Formel x Im erfindungsgemäßen Verfahren ist der Substituent R1 des terminalen Alkins (Formel x) wählbar aus der Reihe Heteroatome aus der Reihe S, Si, N, O, Cl, Br, I, B, lineare und verzweigte C1 - C10-Alkyl oder C1- C10-Aryl, Vinyl oder Heteroaryl aus der Reihe Pyridin, Pyrimidin, Pyridazin, Pyrazin, Triazin, Tetrazin, Pyrrol, Pyrazol, Isoxazol, Imidazol, Oxazol, Thiazol, Thiophen, Furan, lineare und verzweigte C1 - Qo-Alkyloxy oder C1 - Qo-Aryloxy, halogenierte lineare und verzweigte C1 - C10- Alkyl oder halogenierte C1 — Qo-Aryl oder Heteroaryl, lineare und verzweigte C1 — C10 Alkyl- oder C1 — Cio-Arylammocarbonyl, lineare und verzweigte C1 - C10 Acyl, lineare und verzweigte C1 - C10 -Dialkylamino, C1 - C10 Arylamino und können ihrerseits weitere Substituenten aus der Reihe lineare und verzweigte C1 - C10-Alkyl oder C1- C10-Aryl oder Heteroaryl, lineare und verzweigte C1 - Qo-Alkyloxy oder C1 Formula x In the process according to the invention, the substituent R 1 of the terminal alkyne (formula x) is selectable from the series consisting of heteroatoms from the series S, Si, N, O, Cl, Br, I, B, linear and branched C 1 -C 10 -alkyl or C 1 -C 10 -aryl, vinyl or heteroaryl from the series pyridine, pyrimidine, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan, linear and branched C 1 - alkyloxy or C 1 - Qo-aryloxy, halogenated linear and branched C 1 - C 10 - alkyl, or halogenated C 1 - Qo-aryl or heteroaryl, linear and branched C 1 - C 10 alkyl or C 1 - Cio-Arylammocarbonyl linear and branched C 1 -C 10 acyl, linear and branched C 1 -C 10 dialkylamino, C 1 -C 10 arylamino and may themselves be further substituents from the series of linear and branched C 1 -C 10 -alkyl or C 1 -C 10 -Aryl or heteroaryl, linear and branched C 1 - Qo-alkyloxy or C 1

- Qo-Aryloxy, halogenierte lineare und verzweigte C1 - Qo-Alkyl oder halogenierte C1 — Qo-Aryl oder Heteroaryl, lineare und verzweigte C1 — C10 Alkyl- oder C1 — C1O- Arylaminocarbonyl, lineare und verzweigte C1 - C10 Acyl, lineare und verzweigte C1 Qo-aryloxy, halogenated linear and branched C 1 -Qo-alkyl or halogenated C 1 -Qo-aryl or heteroaryl, linear and branched C 1 -C 10 -alkyl or C 1 -C 10 -arylaminocarbonyl, linear and branched C 1 C 10 acyl, linear and branched C 1

- C10 Dialkylamino, C1 - C1O Arylamino, C1 - C10 Diarylamino, Formyl, Oxo, Thio, Hydroxy, Carboxyl, Nitro, Cyano, Nitroso, und Halogene wie F, Cl, Br und I tragen.- C 10 dialkylamino, C 1 - C 1 O arylamino, C 1 - C 10 diarylamino, formyl, oxo, thio, hydroxy, carboxyl, nitro, cyano, nitroso, and halogens such as F, Cl, Br and I.

Als Katalysatoren werden Rutheniumorganylkomplexe eingesetzt, bevorzugt Ruthemum(π)organylkomplexe, besonders bevorzugt Bis(organyll)- Ruthenium(II)komplexe und ganz besonders bevorzugt Bis(2-methylallyl)- Ruthenium(II)komplexe.The catalysts used are ruthenium organyl complexes, preferably ruthenium (II) organyl complexes, particularly preferably bis (organyl) ruthenium (II) complexes, and very particularly preferably bis (2-methylallyl) ruthenium (II) complexes.

Das Ruthenium wird wahlweise durch weitere Liganden aus der Reihe Amine, Phosphine, N-heterocyclische Carbene, Nitrile, Olefine stabilisiert.The ruthenium is optionally stabilized by further ligands from the series amines, phosphines, N-heterocyclic carbenes, nitriles, olefins.

Bevorzugt werden als Liganden Phosphine eingesetzt, besonders bevorzugt werden Phosphine in Kombination mit Aminen eingesetzt, ganz besonders bevorzugt wird eine Kombination aus elektronenreichen Pyridinen und Trialkylphosphinen als Liganden verwendet. Wahlweise können zwei oder mehr dieser Liganden auch in einem Molekül zu einem Chelatliganden vereint werden.Phosphines are preferably used as ligands, particularly preferably phosphines are used in combination with amines, very particularly preferably a combination of electron-rich pyridines and trialkylphosphines is used as ligands. Alternatively, two or more of these ligands may also be combined in a molecule to form a chelating ligand.

Beim erfindungsgemäßen Verfahren wird eine Katalysatormenge von 0,001 mol% bis 20 mol% bezogen auf das Stickstoffderivat eingesetzt. Vorzugsweise wird eine Katalysatormenge von 0,01 mol% bis 3 mol% eingesetzt.In the process according to the invention, a catalyst amount of from 0.001 mol% to 20 mol%, based on the nitrogen derivative, is used. Preferably, a catalyst amount of 0.01 mol% to 3 mol% is used.

Das erfindungsgemäße Verfahren wird bei Temperaturen von -20 °C bis 200 °C, vorzugsweise bei 50 °C bis 200 °C und besonders bevorzugt bei 80 °C bis 120 °C durchgeführt.The inventive method is carried out at temperatures of -20 ° C to 200 ° C, preferably at 50 ° C to 200 ° C and more preferably at 80 ° C to 120 ° C.

Das erfindungsgemäße Verfahren kann in Gegenwart eines Lösungsmittels oder in Substanz durchgeführt werden. Beispielsweise können als Lösungsmittel einer der Einsatzstoffe, Pentan, Hexan, Heptan, Octan, Cyclohexan, Benzol, Toluol, Xylole, Ethylbenzol, Mesitylen, Dioxan, Tetrahydrofuran, Diethylether, Dibutylether, Methyl-t-butylether, Diisopropylether, Diethylenglycol-dimethylether, Methanol, Ethanol, Propanol, Isopropanol, Methylacetat, Ethylacetat, t-Butylacetat, Dimethylformamid, Diethylformarnid, N-Methylpyrrolidon, Dimethylacetamid, Dimethylsulfoxid, Sulfolan, Acetonitril, Propylencarbonat, Propionitril, chlorierte Kohlenwasserstoffe oder Wasser eingesetzt werden.The process according to the invention can be carried out in the presence of a solvent or in bulk. For example, as solvents of one of the starting materials, pentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylenes, ethylbenzene, mesitylene, dioxane, tetrahydrofuran, diethyl ether, dibutyl ether, methyl t-butyl ether, diisopropyl ether, diethylene glycol dimethyl ether, methanol, Ethanol, propanol, isopropanol, methyl acetate, ethyl acetate, t-butyl acetate, dimethylformamide, diethylformamide, N-methylpyrrolidone, dimethylacetamide, dimethylsulfoxide, sulfolane, acetonitrile, propylene carbonate, propionitrile, chlorinated hydrocarbons or water.

Bevorzugt werden aromatische Kohlenwasserstoffe, Amide, Ester und Ether eingesetzt.Aromatic hydrocarbons, amides, esters and ethers are preferably used.

Das erfindungsgemäße Verfahren wird vorzugsweise so durchgeführt, dass die Feststoffe vorgelegt werden und die flüssigen Einsatzstoffe sowie das Lösungsmittel zudosiert werden. Zur Isolierung der erfindungsgemäß hergestellten Produkte wird das Reaktionsgemisch nach Beendigung der Reaktion vorzugsweise destillativ und/oder durch Extraktion oder Kristallisation aufgearbeitet.The process according to the invention is preferably carried out in such a way that the solids are initially introduced and the liquid starting materials and the solvent are metered in. To isolate the products according to the invention, the reaction mixture is preferably worked up by distillation and / or by extraction or crystallization after completion of the reaction.

BeispieleExamples

Die überlegene Aktivität des neuen Katalysatorsystems lässt sich an den Testreaktionen in Tabelle 1 erkennen, die bei lediglich 1000C durchgeführt wurden. Dabei wurde 2-Pyrrolidinon als Amidkomponente benutzt, ein Substrat, das vom Watanabe Katalysator selbst bei hoher Temperatur nicht umgesetzt wird (Eintrag 1).The superior activity of the new catalyst system can be seen in the test reactions in Table 1, which were carried out at only 100 ° C. Here, 2-pyrrolidinone was used as the amide component, a substrate that is not reacted by the Watanabe catalyst even at high temperature (entry 1).

Figure imgf000012_0001
Figure imgf000012_0001

Schema 16. Ru-katalysierte Addition von 2-Pyrrolidinon an l~Hexin.Scheme 16. Ru-catalyzed addition of 2-pyrrolidinone to l-hexyne.

Additiv Ausbeute3 Selektivität"Additive yield 3 selectivity "

Beispiel Ru-Quelle LigandExample Ru Source Ligand

(%) 3.2/ 4.2(%) 3.2 / 4.2

1 Ru3CO12 P(n-bu)3 - 0 n. b.1 Ru 3 CO 12 P (n-bu) 3 - 0 nb

2 (cod)Ru[met]2 P(n-bu)3 49 24:12 (cod) Ru [met] 2 P (n-bu) 3 49 24: 1

3 (cod)Ru[met]2 PCy3 30 3:13 (cod) Ru [met] 2 PCy 3 30 3: 1

4 (cod)Ru[met]2 P(P-FC6H4)S 44 15:1°4 (cod) Ru [met] 2 P (P-FC 6 H 4 ) S 44 15: 1 °

5 (cod)Ru[met]2 PMe3 14 2:15 (cod) Ru [met] 2 PMe 3 14 2: 1

6 (cod)Ru[met]2 Cy2PCH2CH2PCy2 20 1:16 (cod) Ru [met] 2 Cy 2 PCH 2 CH 2 PCy 2 20 1: 1

7 (cod)Ru[met]2 Cy2PCH2PCy2 50 1:37 (cod) Ru [met] 2 Cy 2 PCH 2 PCy 2 50 1: 3

8 (cod)Ru[met]2 P(C6Hs)3 40 30:18 (cod) Ru [met] 2 P (C 6 Hs) 3 40 30: 1

9 (cod)Ru[met]2 P(n-bu)3 - 49 24:19 (cod) Ru [met] 2 P (n-bu) 3 - 49 24: 1

10 (PPh3)2Ru[met]2 - - 26 27:110 (PPh3) 2 Ru [met] 2 - - 26 27: 1

11 (cod)Ru[met]2 P(n-bu)3 92 16:1

Figure imgf000012_0002
12 (cod)Ru[met]2 P(n-bu)3 50 6:1
Figure imgf000013_0001
11 (cod) Ru [met] 2 P (n-bu) 3 92 16: 1
Figure imgf000012_0002
12 (cod) Ru [met] 2 P (n-bu) 3 50 6: 1
Figure imgf000013_0001

13 (cod)Ru[met]2 P(n-bu)3 S X^, 98 28:113 (cod) Ru [met] 2 P (n-Bu) 3 SX ^, 98 28: 1

VV

N ^N ^

14 (cod)Ru[met]2 P(n-bu)3 75 6:114 (cod) Ru [met] 2 P (n-bu) 3 75 6: 1

15 (cod)Ru[met]2 P(n-bu)3 57 5:115 (cod) Ru [met] 2 P (n-bu) 3 57 5: 1

16 (cod)Ru[met]2 P(n-bu)3 50 5:1

Figure imgf000013_0002
16 (cod) Ru [met] 2 P (n-bu) 3 50 5: 1
Figure imgf000013_0002

Reaktionsbedingungen: 0.50 mmol Pyrrolidin-2-on, 1.00 mmol 1-Hexin, 0.01 mmol Ru-Quelle, 0.06 mmol Ligand, Toluol, 100 0C, 15 h; a) GC-Aubeuten mit n- Tetradecan als internem Standard; b) Diastereomerenverhältnis nach GC;Reaction conditions: 0.50 mmol pyrrolidin-2-one, 1.00 mmol 1-hexyne, 0.01 mmol Ru source, 0.06 mmol ligand, toluene, 100 0 C, 15 h; a) GC yields with n-tetradecane as internal standard; b) diastereomer ratio according to GC;

Wie aus Tabelle 1 ersichtlich zeigen Kombinationen der Rutheniumverbindung Bis(2-methylallyl)-l,5-cyclooctadienruthenium(II) = (cod)Ru[met]2 mit verschiedenen Phosphinen überraschend eine hervorragende Aktivität für die gewünschte Umsetzung. Es ist bemerkenswert, dass die Regioselektivität der Addition durch die Natur des Phosphins abgestimmt werden kann (Eintrag x und x). Es ist weiterhin ersichtlich, dass sich der Zusatz basischer Amine, und insbesondere elektronenreicher Pyridine überaus positiv auf Umsätze und Selektivitäten auswirkt. Auch präformierte Rutheniumphosphinkomplexe wie (Methallyl)2Ru(PPh3)2 (PPh3 = Triphenylphosphin) sind wirksame Katalysatoren (Beispiel xx)As shown in Table 1, combinations of the ruthenium compound bis (2-methylallyl) -l, 5-cyclooctadienruthenium (II) = (cod) Ru [met] 2 with various phosphines surprisingly show excellent activity for the desired reaction. It is noteworthy that the regioselectivity of addition can be tuned by the nature of the phosphine (entry x and x). It can also be seen that the addition of basic amines, and in particular electron-rich pyridines, has a very positive effect on conversions and selectivities. Also, preformed ruthenium phosphine complexes such as (methallyl) 2 Ru (PPh 3 ) 2 (PPh 3 = triphenylphosphine) are effective catalysts (Example xx)

Beispiel 17. N-((p)-Hex-l-enyl)pyrrolidin-2-on Example 17. N - ((p) -hex-1-enyl) pyrrolidin-2-one

Figure imgf000014_0001
Figure imgf000014_0001

In ein 2O mL Bördelkappengefaß wurden nacheinander Bis-(2-methylallyl)- cycloocta-l,5-dien-Ruthenium(IT) (6.4 mg, 0.02 mmol), Tri-n-butylphosphan (15 μL, 0.04 mmol), Pyrrolidin-2-on (1.2) (85.1 mg, 1 mmol), Dimethylaminopyridin (4.9 mg, 0.4 mmol), 1.5 mL Toluol und 1 -Hexin (2.1) (229 μL, 2 mmol) gegeben. Das Reaktionsgefäß wurde verschlossen und auf 100 C erwärmt. Der Reaktionsverlauf wurde mittels Gaschromatographie verfolgt. Nach vollständigem Umsatz (4-5 Stunden) wurde das Lösungsmittel am Rotationsverdampfer entfernt, der verbleibende Rückstand auf Kieselgel aufgezogen und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) aufgereinigt. Auf diese Weise wurde 3.2 (153.9 mg, 92 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.2:4.2 betrag 25:1.Bis (2-methylallyl) -cycloocta-1, 5-diene-ruthenium (IT) (6.4 mg, 0.02 mmol), tri-n-butylphosphine (15 μL, 0.04 mmol), pyrrolidine were successively added to a 2 ml flask cap. Add 2-one (1.2) (85.1 mg, 1 mmol), dimethylaminopyridine (4.9 mg, 0.4 mmol), 1.5 mL of toluene and 1-hexine (2.1) (229 μL, 2 mmol). The reaction vessel was sealed and heated to 100 ° C. The course of the reaction was monitored by gas chromatography. After complete conversion (4-5 hours), the solvent was removed on a rotary evaporator, the residue remaining on silica gel and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.2 (153.9 mg, 92% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.2: 4.2 was 25: 1.

1H-NMR (300.1 MHz, CDCl3): δ = 6.86 (d, 3J= 14.7 Hz, IH5 H-5), 4.92 (dt, 3J= 14.7 Hz5 7.2 Hz, IH, H-6), 3.48 (t, 3J= 7.2 Hz, 2H, H-4), 2.46 (t, 3J= 8.1 Hz5 2H5 H-2), 2.01-2.14 (m, 4H5 H-7. 3), 1.24-1.39 (m, 4H5 H-8, 9), 0.88 (t, 3J= 7.2 Hz, 3H, H-10) ppm. 1 H-NMR (300.1 MHz, CDCl 3 ): δ = 6.86 (d, 3 J = 14.7 Hz, IH 5 H-5), 4.92 (dt, 3 J = 14.7 Hz 5 7.2 Hz, IH, H-6) , 3.48 (t, 3 J = 7.2 Hz, 2H, H-4), 2.46 (t, 3 J = 8.1 Hz 5 2H 5 H-2), 2.01-2.14 (m, 4H 5 H-7, 3), 1.24-1.39 (m, 4H 5 H-8, 9), 0.88 (t, 3 J = 7.2 Hz, 3H, H-10) ppm.

13C-NMR (75.5 MHz5 CDCl3): δ = 172.2 (C-I), 123.6 (C-5), 112.5 (C-6), 45.3 (C- 4), 32.3 (C-7), 31.3 (C-2), 29.7 (C-8), 22.1 (C-9), 17.4 (C-3), 13.9 (C-10) ppm. 13 C-NMR (75.5 MHz 5 CDCl 3): δ = 172.2 (CI), 123.6 (C-5), 112.5 (C-6), 45.3 (C-4), 32.3 (C-7), 31.3 (C -2), 29.7 (C-8), 22.1 (C-9), 17.4 (C-3), 13.9 (C-10) ppm.

MS (EI3 70 eV, Verdampfungstemperatur 10 °C): m/z (%) = 167 (2O)5 124MS (EI 3 70 eV, evaporation temperature 10 ° C): m / z (%) = 167 (2O) 5 124

(100), 86 (23), 69 (12), 41 (21)(100), 86 (23), 69 (12), 41 (21)

HRMS (EI) berechnet für C10H17NO: 167.131014 u, gefunden: 167.130871 u. Beispiel 18. (N)-((Z)-Hex-l-enyl)pyrrolidin-2-on (4.2)HRMS (EI) calculated for C 10 H 17 NO: 167.131014 u, found: 167.130871 u. Example 18. (N) - ((Z) -hex-1-enyl) pyrrolidin-2-one (4.2)

Figure imgf000015_0001
Figure imgf000015_0001

In ein 2O mL Bördelkappengefäß wurden nacheinander (cod)Ru(η3-2-MeC3H4)2 (6.4 mg, 0.02 mmol), Bis(dicyclophosphino)methan (12.3 mg, 0.03 mmol), Pyrrolidin-2-on (1.2) (85.1 mg, 1 mmol), 1.5 mL Toluol, 1-Hexin (2.1) (229 μL, 2 mmol) und Wasser (vorher mit Argon gesättigt, 144 μL, 8 mmol) gegeben. Das Reaktionsgefäß wurde verschlossen und auf 100 0C erwärmt. Der Reaktionsverlauf wurde mittels Gaschromatographie verfolgt. Nach vollständigem Umsatz wurde das Lösungsmittel am Rotationsverdampfer entfernt,, der verbleibende Rückstand auf Kieselgel aufgezogen und mittels Säulenchromatographie (SiO2, iso- Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80)aufgereinigt Auf diese Weise wurde 4.2 (141 mg, 84% d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.2:4.2 betrug 1:5.In a 2O mL crimp cap flask were successively (cod) Ru (η 3 -2 MeC 3 H 4) 2 (6.4 mg, 0.02 mmol), bis (dicyclophosphino) methane (12.3 mg, 0.03 mmol), pyrrolidin-2-one (1.2 ) (85.1 mg, 1 mmol), 1.5 mL of toluene, 1-hexyne (2.1) (229 μL, 2 mmol) and water (previously saturated with argon, 144 μL, 8 mmol). The reaction vessel was closed and heated to 100 0 C. The course of the reaction was monitored by gas chromatography. After complete conversion, the solvent was removed on a rotary evaporator, the residue remaining was applied to silica gel and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). 4.2 (141 mg, 84% of theory) as a yellowish oil. The diastereomer ratio (E: Z) 3.2: 4.2 was 1: 5.

1H-NMR (300.1 MHz, CDCl3): δ = 6.30 (d, 3J= 9.7 Hz, IH5 H-5), 3.69 (dt, 3J= 9.7 Hz, 7.5 Hz, IH, H-6), 3.69 (t, 3J= 7.2 Hz, 2H, H-4), 2.34 (t, 3J= 8.3 Hz, 2H5 H-2), 1.99-2.14 (m, 4H, H-7, 3), 1.21-1.36 (m, 4H5 H-8, 9), 0.84 (t, 3J= 7.2 Hz5 3H5 H-10) ppm. 1 H-NMR (300.1 MHz, CDCl 3 ): δ = 6.30 (d, 3 J = 9.7 Hz, IH 5 H-5), 3.69 (dt, 3 J = 9.7 Hz, 7.5 Hz, IH, H-6) , 3.69 (t, 3 J = 7.2 Hz, 2H, H-4), 2.34 (t, 3 J = 8.3 Hz, 2H 5 H-2), 1.99-2.14 (m, 4H, H-7, 3), 1.21-1.36 (m, 4H 5 H-8, 9), 0.84 (t, 3 J = 7.2 Hz 5 3H 5 H-10) ppm.

13C-NMR (75.5 MHz, CDCl3): δ = 174.9 (C-I), 122.6 (C-5), 117.3 (C-6), 49.0 (C- 4), 32.8 (C-7), 30.7 (C-2)5 27.3 (C-8)5 22.6 (C-9), 19.0 (C-3), 14.3 (C-10) ppm. 13 C-NMR (75.5 MHz, CDCl 3): δ = 174.9 (CI), 122.6 (C-5), 117.3 (C-6), 49.0 (C-4), 32.8 (C-7), 30.7 (C -2) 5 27.3 (C-8) 5 22.6 (C-9), 19.0 (C-3), 14.3 (C-10) ppm.

MS (EI, 70 eV, Verdampfungstemperatur 10 °C): m/z (%) = 167 (20), 124MS (EI, 70 eV, evaporation temperature 10 ° C): m / z (%) = 167 (20), 124

(100), 86 (25), 69 (16), 41 (27) HRMS (ESIpos) berechnet für C10H17NO-Na: 190.120783 [M+] u, gefunden: 190.12105u(100), 86 (25), 69 (16), 41 (27) HRMS (ESIpos) calculated for C 10 H 17 NO-Na: 190.120783 [M +] u, found: 190.12105u

Beispiel XX. ~N-((E)-Hex-l-enyl)azetidin-2-on (3.3)Example XX. ~ N - ((E) -hex-1-enyl) azetidin-2-one (3.3)

Die Verbindung wurde analog zu Verbindung 3.2aus Azetidin-2-on (1.3) (71.1 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.3 (104 mg, 70 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.3:4.3 betrug 2:1.The compound was prepared analogously to compound 3.2 of azetidin-2-one (1.3) (71.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way 3.3 (104 mg, 70% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.3: 4.3 was 2: 1.

Beispiel 19. Η-((ß)-Hex-l-enyl)piperidon (3.4)Example 19. Η - ((β) -hex-1-enyl) piperidone (3.4)

Die Verbindung wurde analog zu Verbindung 3.2 aus Pipridin-2-on (1.4) (99.1 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.4 (165 mg, 70 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.4:4.4 betrug 30:1.The compound was prepared analogously to compound 3.2 from pipridin-2-one (1.4) (99.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.4 (165 mg, 70% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.4: 4.4 was 30: 1.

Beispiel 20. N-((E)-Hex-l-enyl)azonan-2-on (3.5)Example 20. N - ((E) -hex-1-enyl) azonan-2-one (3.5)

Die Verbindung wurde analog zu Verbindung 3.2 aus Azepan-2-on (1.5) (113.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.5 (179 mg, 94 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.5:4.5 betrug 30:1.The compound was prepared analogously to compound 3.2 from azepan-2-one (1.5) (113.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.5 (179 mg, 94% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.5: 4.5 was 30: 1.

Beispiel 21. N-((E)-Hex-l-enyl)-azonan~2-on (3.6) Die Verbindung wurde analog zu Verbindung 3.2 aus Azonan-2-on (1,6) (141.2 mg, 1.0 mmol) und 1 -Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.6 (186 mg, 86 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.6:4.6 betrug 30: 1.Example 21. N - ((E) -hex-1-enyl) -azonane-2-one (3.6) The compound was prepared analogously to compound 3.2 from azonan-2-one (1.6) (141.2 mg, 1.0 mmol) and 1-hexine (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / Ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.6 (186 mg, 86% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.6: 4.6 was 30: 1.

Beispiel 22. ~H-((E)-Hex-l-enyl)-N-(phenyl)acetamid (3.7)Example 22. ~ H - ((E) -hex-1-enyl) -N- (phenyl) -acetamide (3.7)

Die Verbindung wurde analog zu Verbindung 3.2 aus N-Phenylacetamid (1.7) (135.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.7 (196 mg, 90 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.7:4.7 betrug 30:1The compound was prepared analogously to compound 3.2 from N-phenylacetamide (1.7) (135.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way, 3.7 (196 mg, 90% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.7: 4.7 was 30: 1

Beispiel 23. Υ$-((E)-Hex-l-enyl)-N-(methyl)benzamid (3.8)Example 23. Υ $ - ((E) -hex-1-enyl) -N- (methyl) benzamide (3.8)

Die Verbindung wurde analog zu Verbindung 3.2 aus N-Methylbenzamid (1.8) (135.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie ((SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80)) gereinigt. Auf diese Weise wurde 3.8 (98 mg, 46 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.8:4.8 betrug 16:1.The compound was prepared analogously to compound 3.2 from N-methylbenzamide (1.8) (135.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, Gradient elution: 100/0 to 20/80)). In this way, 3.8 (98 mg, 46% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.8: 4.8 was 16: 1.

Beispiel 24. ~N-(4-Acetyl-phenyl)-Η-((E)-hex-l-enyl)acetamid (3.9) Die Verbindung wurde analog zu Verbindung 3.2 aus N-(4-Acetyl-phenyl)-acetamid (1.9) (177.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.9 (84 mg, 33 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.9:4.9 betrug 30:1. Beispiel 25. N-(4-Ethoxy-phenyl)-N-((E)-hex-l-enyl)acetamid (3.10)Example 24. ~ N- (4-Acetyl-phenyl) -Η- ((E) -hex-1-enyl) -acetamide (3.9) The compound was analogous to compound 3.2 from N- (4-acetyl-phenyl) -acetamide (1.9) (177.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). cleaned. In this way, 3.9 (84 mg, 33% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.9: 4.9 was 30: 1. Example 25. N- (4-Ethoxy-phenyl) -N - ((E) -hex-1-enyl) -acetamide (3.10)

Die Verbindung wurde analog zu Verbindung 3.2 aus N-(4-Ethoxy-phenyl)-acetamidThe compound was analogous to compound 3.2 from N- (4-ethoxy-phenyl) -acetamide

(1.10) (179.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution:(1.10) (179.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution:

100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.10 (252 mg, 94 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.10:4.10 betrug100/0 to 20/80). In this way 3.10 (252 mg, 94% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) was 3.10: 4.10

30:1.30: 1st

Beispiel 26. N-((E)-Hex-l-enyl)-N-(methyl)formamid (3.12)Example 26. N - ((E) -hex-1-enyl) -N- (methyl) formamide (3.12)

Die Verbindung wurde analog zu Verbindung 3.2 aus N-Methylformamid (1.12) (59.1 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.12 (110 mg, 83 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.12:4.12 betrug 30:1, Rotamerenverhältnis 3:1.The compound was prepared analogously to compound 3.2 from N-methylformamide (1.12) (59.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way, 3.12 (110 mg, 83% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.12: 4.12 was 30: 1, rotamer ratio 3: 1.

Beispiel xx. ~N-((E)-Hex-l-enyl)-N-(methyl)acetamid (3.13)Example xx. ~ N - ((E) -hex-1-enyl) -N- (methyl) acetamide (3.13)

Die Verbindung wurde analog zu Verbindung 3.2 aus N-Methylacetamid (1.13) (73.1 mg, 1.0 mmol) und 1 -Hexin (B.l) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.13 (126 mg, 84 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.13:4.13 betrug 30:1, Rotamerenverhältnis 2:1.The compound was prepared analogously to compound 3.2 from N-methylacetamide (1.13) (73.1 mg, 1.0 mmol) and 1 -hexine (B1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.13 (126 mg, 84% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.13: 4.13 was 30: 1, rotamer ratio 2: 1.

Beispiel 27. ~N-((E)-Hex-l-enyl)-~N-(isopropyl)acrylamid (3.14) Die Verbindung wurde analog zu Verbindung 3.2 aus N-rlsopropylacrylamid (1.14) (113.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.14 (74 mg, 38 % d. Th.) als farbloses Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.14:4.14 betrug 30: 1.Example 27. ~ N - ((E) -Hex-1-enyl) ~ N- (isopropyl) acrylamide (3.14) The compound was prepared analogously to compound 3.2 from N-rlsopropylacrylamide (1.14) (113.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.14 (74 mg, 38% of theory) was obtained as a colorless oil. The diastereomer ratio (E: Z) 3.14: 4.14 was 30: 1.

Beispiel 28. l,4-Di-((E)-hex-l-enyl)piperazin-2,5~dion (3.15) Die Verbindung wurde analog zu Verbindung 3.2 aus Piperidin-2,5-dion (1.15) (114.1 mg, 1.0 mmol) und 1-Hexin (2.1) (458 μL, 4.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.15 (259.1 mg, 99 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.15:4.15 betrug 30:1.Example 28. 1,4-Di - ((E) -hex-1-enyl) piperazine-2,5-dione (3.15) The compound was prepared analogously to compound 3.2 from piperidine-2,5-dione (1.15) (114.1 mg, 1.0 mmol) and 1-hexyne (2.1) (458 μL, 4.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.15 (259.1 mg, 99% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.15: 4.15 was 30: 1.

Beispiel 29. l,3-Di-((E)-hex-l-enyl)imidazolidin-2-on (3.16)Example 29. 1,3-Di - ((E) -hex-1-enyl) imidazolidin-2-one (3.16)

Die Verbindung wurde analog zu Verbindung 3.2 aus Imidazolidin-2-on (1.16)The compound was prepared analogously to compound 3.2 from imidazolidin-2-one (1.16).

(86.1 mg, 1.0 mmol) und 1-Hexin (2.1) (458 μL, 4.0 mmol) dargestellt und mittels(86.1 mg, 1.0 mmol) and 1-hexyne (2.1) (458 μL, 4.0 mmol) and by means of

Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bisColumn chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to

20/80) . gereinigt. Auf diese Weise wurde 3.16 (175.3 mg, 70 % d. Th.) als gelbstichiger Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.16:4.16 betrug20/80). cleaned. In this way 3.16 (175.3 mg, 70% of theory) was obtained as a yellowish solid. The diastereomer ratio (E: Z) was 3.16: 4.16

30:1.30: 1st

Beispiel 30. (4S, 5K)-^-((E)-Hex-l~enyl)-3,4-(dimethyl)-5-phenyl)imidazolidin-2-on Die Verbindung wurde analog zu Verbindung 3.2 aus l,5(S)-Dimehyl-4(R)-phenyl~ imidazolidin-2-on (1.17) (190.3 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.17 (262 mg, 99 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.17:4.17 betrug 23: 1.Example 30. (4S, 5K) - ^ - ((E) -hex-enyl) -3,4- (dimethyl) -5-phenyl) imidazolidin-2-one The compound was prepared analogously to compound 3.2 from I, 5 (S) -dimethyl-4 (R) -phenyl-imidazolidin-2-one (1.17) (190.3 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.17 (262 mg, 99% of theory) was used as colorless solid. The diastereomer ratio (E: Z) 3.17: 4.17 was 23: 1.

Beispiel 31. (2S)-N-((E)-Hex-l~enyl)-5-(oxo--pyrrolidin)-2-carbonsäuremethylester Die Verbindung wurde analog zu Verbindung 3.2 aus 5-Oxo-pyrrolidin-2(S)- carbonsäuremethylester (1.18) (143.1 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso- Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.18 (210.3 mg, 96 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.18:4.18 betrug 6:1.Example 31. (2S) -N - ((E) -hex-enyl) -5- (oxo-pyrrolidine) -2-carboxylic acid methyl ester The compound was prepared analogously to compound 3.2 from 5-oxopyrrolidin-2 (p ) - Carboxylic acid methyl ester (1.18) (143.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20 / 80). In this way, 3.18 (210.3 mg, 96% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.18: 4.18 was 6: 1.

Beispiel 32. 3-((E)-Hex-l-enyl)oxazolidin-2-on (3.19)Example 32. 3 - ((E) -hex-1-enyl) oxazolidin-2-one (3.19)

Die Verbindung wurde analog zu Verbindung 3.2 aus Oxalidin-2-on (1.19) (87.1 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.19 (147.9 mg, 90.1 % d. Th.) als farbloses Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.19:4.19 betrug 23:1.The compound was prepared analogously to compound 3.2 from oxalidin-2-one (1.19) (87.1 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way, 3.19 (147.9 mg, 90.1% of theory) was obtained as a colorless oil. The diastereomer ratio (E: Z) 3.19: 4.19 was 23: 1.

Beispiel 33. (4S)-3-((E)-Hex-l-enyl)-4-(isopropyl)-oxazoύdin-2-on (3.20) Verbindung wurde analog zu Verbindung 3.2 aus 4(S)-Isopropyl-oxalidin-2-on (1.20) (129.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.20 (198.9 mg, 97 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.20:4.20 betrug 30:1. Beispiel 34. (4R, 5S)-3-((E)-Hex-l-enyl)-5-(methyl)-4-(phenyϊ)oxazolidin-2-on (3.21) Die Verbindung wurde analog zu Verbindung 3.2 aus 5(S)-Methyl-4(R)-phenyl- oxalidin-2-on (1.21) (177.2 mg, 1.0 mmol) und 1-Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.21 (211.1 mg, 84 % d. Th.) als farbloser Feststoff erhalten.Das Diastereomerenverhältnis (E:Z) 3.21:4.21 betrug 21:1.Example 33. (4S) -3 - ((E) -hex-1-enyl) -4- (isopropyl) -oxazo-din-2-one (3.20) Compound became analogous to compound 3.2 from 4 (S) -isopropyl-oxalidine 2-one (1.20) (129.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.20 (198.9 mg, 97% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.20: 4.20 was 30: 1. Example 34. (4R, 5S) -3 - ((E) -hex-1-enyl) -5- (methyl) -4- (phenyl) oxazolidin-2-one (3.21) The compound was analogous to compound 3.2 5 (S) -methyl-4 (R) -phenyl-oxalidin-2-one (1.21) (177.2 mg, 1.0 mmol) and 1-hexyne (2.1) (229 μL, 2.0 mmol) and by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.21 (211.1 mg, 84% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.21: 4.21 was 21: 1.

Beispiel 35. ~N-((E)-Hex-l-enyl)pyrrolidin-2,5~dion (4.22)Example 35. ~ N - ((E) -hex-1-enyl) pyrrolidine-2,5-dione (4.22)

Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2,5-dion (1.22) (99.1 mg, 1.0 mmol) und Hexin (2.1) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 4.22 (22 mg, 12 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.22:4.22 betrug 1:2 (laut GC). Nach der Säulenchromatographie wurde nur das Z-Diastereomere erhalten.The compound was prepared analogously to compound 3.2 from pyrrolidine-2,5-dione (1.22) (99.1 mg, 1.0 mmol) and hexine (2.1) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate , Gradient elution: 100/0 to 20/80). In this way 4.22 (22 mg, 12% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.22: 4.22 was 1: 2 (according to GC). After column chromatography, only the Z-diastereomer was obtained.

Beispiel 36. (2Ε)-3-(2-Oxopyrrolidin-l-yl)-propensäuremethylester (3.23) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und Acrylsäuremethylester (2.2) (178 μL, 2.0 mmol) dargestellt und mittels (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.23 (211.1 mg, 84 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.23:4.23 betrug 30:1.Example 36. (2Ε) -3- (2-Oxopyrrolidin-1-yl) -propenoic acid methyl ester (3.23) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and methyl acrylate (2.2 ) (178 μL, 2.0 mmol) and purified by means of (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.23 (211.1 mg, 84% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.23: 4.23 was 30: 1.

Beispiel 37. ~N-((E)-3-Methoxy-prop-l-enyl)-pyrrolidin-2-on (3.24) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und 3-Methoxy-propin (2.3) (169 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis •20/80) gereinigt. Auf diese Weise wurde 3.24 (145 mg, 93 % d. Th.) als farbloses Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.24:4.24 betrug 8:1.Example 37. ~ N - ((E) -3-Methoxy-prop-1-enyl) -pyrrolidin-2-one (3.24) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and 3-methoxy-propyne (2.3) (169 μL, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to • 20/80). In this way 3.24 (145 mg, 93% of theory) was obtained as a colorless oil. The diastereomer ratio (E: Z) 3.24: 4.24 was 8: 1.

Beispiel 38. ~N-((ß)-3,3-Dimethyl-but-l-enyl)pyrrolidin-2-on (3.26) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und 3,3-Dimethyl-but-l-in (2.5) (246 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.26 (161.8 mg, 99 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.26:4.26 betrug 30:1. -. ..Example 38. ~ N - ((β) -3,3-Dimethylbut-1-enyl) pyrrolidin-2-one (3.26) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL , 1.0 mmol) and 3,3-dimethyl-but-1-one (2.5) (246 μL, 2.0 mmol) and by means of column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20 / 80). In this way 3.26 (161.8 mg, 99% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.26: 4.26 was 30: 1. -. ..

Beispiel 39. N-((E)-3-Methyl-l,3-di-l-enyl)pyrrolidin-2-on (3.27) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und 2-Methyl-but-l-en-3-in (2.6) (190 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradieriten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.27 (141.2 mg, 99 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.27:4.27 betrug 24:1. .Example 39. N - ((E) -3-Methyl-1,3-di-1-enyl) pyrrolidin-2-one (3.27) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and 2-methyl-but-1-en-3-yn (2.6) (190 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, Gradierite elution: 100/0 until 20/80). In this way 3.27 (141.2 mg, 99% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.27: 4.27 was 24: 1. ,

Beispiel 40. T$-((E)-2-TrimethylsϊlyLvinyl)pyrroHdin-2-on (3.28) Die Verbindung wurde analog zu Verbindung 3.1 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und Ethinyl-trimethylsilan (2.7) (277 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.28 (120.0 mg, 70 % d. Th.) als farbloses Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.28:4.28 betrug 3:1. Beispiel 41. 'N-(ß)-2-phenyl-vinyl)pyrrolidin-2-on (3.29)Example 40. T $ - ((E) -2-trimethylsylvinyl) pyrrolidin-2-one (3.28) The compound was prepared analogously to compound 3.1 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and ethynyl-trimethylsilane (2.7) (277 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.28 (120.0 mg, 70% of theory) was obtained as a colorless oil. The diastereomer ratio (E: Z) 3.28: 4.28 was 3: 1. Example 41. ' N- (β) -2-phenyl-vinylpyrrolidin-2-one (3.29)

Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und Phenylacetyen (2.8) (220 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.29 (180.0 mg, 99 % d. Th.) als gräulicher Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.29:4.29 betrug 22:1.The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and phenylacetyene (2.8) (220 μL, 2.0 mmol) and by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient Elution: 100/0 to 20/80). In this way 3.29 (180.0 mg, 99% of theory) was obtained as a grayish solid. The diastereomer ratio (E: Z) 3.29: 4.29 was 22: 1.

Beispiel 42. N-((E)-4-Phenyl-but-l-enyl)pyrrolidin-2-on (3.30) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und But-3-ynil-benzol (2.9) (281 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.30 (201.6 mg, 99 % d. Th.) als farbloser Feststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.30:4.30 betrug 30:1.Example 42. N - ((E) -4-Phenyl-but-1-enyl) pyrrolidin-2-one (3.30) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol and but-3-ynilbenzene (2.9) (281 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.30 (201.6 mg, 99% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.30: 4.30 was 30: 1.

Beispiel 43. Yl-((Z)-4-Phenyl-but-l-enyl)pyrrolidin-2-on (4.30) Die Verbindung wurde analog zu Verbindung 4.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und But-3-ynü-benzol (2.9) (281 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 4.30 (198 mg, 92 % d. Th.) als farbloserFeststoff erhalten. Das Diastereomerenverhältnis (E:Z) 3.30:4.30 betrug 1:8.Example 43. Yl - ((Z) -4-Phenyl-but-1-enyl) pyrrolidin-2-one (4.30) The compound was prepared analogously to compound 4.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol and but-3-yn-benzene (2.9) (281 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 4.30 (198 mg, 92% of theory) was obtained as a colorless solid. The diastereomer ratio (E: Z) 3.30: 4.30 was 1: 8.

Beispiel 44. 1$-((E)-Dodeca-l,ll-dienyl)pyrrolidin-2-on (3.31) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und Dodec-1-en-ll-in (2.10) (463 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.31 (241.1 mg, 99 % d. Th.) als gelbliches Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.31:4.31 betrug 30:1.Example 44. 1 $ - ((E) -dodeca-1,1-dienyl) pyrrolidin-2-one (3.31) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol). and dodec-1-en-II-in (2.10) (463 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.31 (241.1 mg, 99% of theory) was obtained as a yellowish oil. The diastereomer ratio (E: Z) 3.31: 4.31 was 30: 1.

Beispiel 45. ~N-((E)-Hepta-l,6-dienyl)pyrrolidin-2-on (3.32)Example 45. ~ N - ((E) -hepta-1,6-dienyl) pyrrolidin-2-one (3.32)

Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und Hept-l-en-6-in (2.11) (188.3 mg, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.23 (170.3 mg, 95 % d. Th.) als farbloses Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.32:4.32 betrug 30:1.The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and hept-l-en-6-yn (2.11) (188.3 mg, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.23 (170.3 mg, 95% of theory) was obtained as a colorless oil. The diastereomer ratio (E: Z) 3.32: 4.32 was 30: 1.

Beispiel 46. N-((E)-5-Chloro-pent-l-enyl)pyrrolidin-2-on (3.33) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und 5-Chloro-pent-l-in (2.12) (212 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.33 (148 mg, 80 % d. Th.) als farbloses Öl erhalten. Das Diastereomerenverhältnis (E:Z) 3.33:3.43 betrug 30:1.Example 46. N - ((E) -5-chloropent-1-enyl) pyrrolidin-2-one (3.33) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol and 5-chloro-pent-l-in (2.12) (212 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way 3.33 (148 mg, 80% of theory) was obtained as a colorless oil. The diastereomer ratio (E: Z) 3.33: 3.43 was 30: 1.

Beispiel 47. (2Z)-2-(2-oxopyrrolidin-l-yl)-3-phenylacrylsäuremethylester (3.34) Die Verbindung wurde analog zu Verbindung 3.2 aus Pyrrolidin-2-on (1.1) (77 μL, 1.0 mmol) und Phenyl-propionsäureethylester (2.13) (229 μL, 2.0 mmol) dargestellt und mittels Säulenchromatographie (SiO2, iso-Hexan/Essigester, Gradienten-Elution: 100/0 bis 20/80) gereinigt. Auf diese Weise wurde 3.34 (154 mg, 63 % d. Th.) als gelblicher Feststoff erhalten. Das Isomerenverhältnis zwischen der oben beschriebenen Verbindung und den 3 weiteren Isomeren betrug 30: 1. Example 47. (2Z) -2- (2-oxopyrrolidin-1-yl) -3-phenylacrylic acid methyl ester (3.34) The compound was prepared analogously to compound 3.2 from pyrrolidin-2-one (1.1) (77 μL, 1.0 mmol) and phenyl ethyl propionate (2.13) (229 μL, 2.0 mmol) and purified by column chromatography (SiO 2 , iso-hexane / ethyl acetate, gradient elution: 100/0 to 20/80). In this way, 3.34 (154 mg, 63% of theory) was obtained as a yellowish solid. The isomer ratio between the above-described compound and the other 3 isomers was 30: 1.

Claims

Patentansprüche claims 1. Verfahren zur Herstellung von N-Alkenylverbindungen durch Umsetzung von N-1. Process for the preparation of N-alkenyl compounds by reacting N-alkenyl compounds H- Verbindungen mit terminalen Alkinen in Gegenwart katalytischer Mengen an Rutheniumorganylkomplexen.H compounds with terminal alkynes in the presence of catalytic amounts of ruthenium organyl complexes. 2. Verfahren nach Anspruch 1, wobei als Katalysator ein Ruthenium(II)- organylkomplex eingesetzt wird.2. The method according to claim 1, wherein the catalyst used is a ruthenium (II) organyl complex. 3. Verfahren nach Anspruch 1, wobei als Katalysator ein Bis(organyl)-3. The method of claim 1, wherein as a bis (organyl) - Ruthenium(II)komplex eingesetzt wird.Ruthenium (II) is used complex. 4. Verfahren nach Anspruch 1, wobei als Katalysator ein Bis(2-methylallyl)-4. The method according to claim 1, wherein the catalyst is a bis (2-methylallyl) - Ruthenium(II)komplex eingesetzt wird.Ruthenium (II) is used complex. 5. Verfahren nach einem der Ansprüche 1-4, wobei der Katalysator durch weitere5. The method according to any one of claims 1-4, wherein the catalyst by further Liganden aus der Reihe Amine, Phosphine, N-heterocyclische Carbene, Nitrile, Olefine stabilisiert wird.Ligands from the series amines, phosphines, N-heterocyclic carbenes, nitriles, olefins is stabilized. 6. Verfahren nach Anspruch 5 wobei der Katalysator durch Phosphinliganden stabilisiert wird.6. The method of claim 5 wherein the catalyst is stabilized by phosphine ligands. 7. Verfahren nach Anspruch 5, wobei der Phosphinligand drei Alkylsubstituenten trägt.7. The method of claim 5, wherein the phosphine ligand carries three alkyl substituents. 8. Verfahren nach Anspruch 5, wobei das Katalysatorsystem ein Amin enthält.The process of claim 5 wherein the catalyst system contains an amine. 9. Verfahren nach Anspruch 8, wobei als Amin ein elektronenreiches Pyridin eingesetzt wird. 9. The method of claim 8, wherein as the amine, an electron-rich pyridine is used. 10. Verfahren nach einem der Ansprüche 1-9 wobei die N-H- Verbindung der allgemeinen Formel xx entspricht10. The method according to any one of claims 1-9 wherein the N-H compound corresponds to the general formula xx H-N R3 wobei die Substituenten R2 und R3 unabhängig voneinander wählbar sind aus der Reihe Heteroatome aus der Reihe H, S, Si, N, O, Cl, Br, I, B, lineare und verzweigte C1 — C10-Alkyl oder C1- C10-Aryl oder Heteroaryl, lineare und verzweigte C1 — C10- Vinyl- oder Heteroaryl aus der Reihe Pyridin, Pyrimidin, Pyridazin, Pyrazin, Triazin, Tetrazin, Pyrrol, Pyrazol, Isoxazol, Imidazol, Oxazol, Thiazol, Thiophen, Furan, lineare und verzweigte C1 - C10-Alkyloxy oder C1 - Qo-Aryloxy, halogenierte lineare und verzweigte Ci - Q0- Alkyl oder halogenierte C1 - CiO-Aryl oder Heteroaryl, lineare und verzweigte Ci - Ci0 Alkyl- oder C1 - Qo-Arylaminocarbonyl, lineare und verzweigte Ci - Ci0 Acyl, lineare und verzweigte C1 - C10 -Dialkylamino, C1 - C10 Arylamino oder gemeinsam Bestandteil einer cyclischen C1 - Qo- gesättigten oder ungesättigten Alkyl-, Aryl-, oder Heteroaryleinheit und sind und ihrerseits weitere Substituenten aus der Reihe lineare und verzweigte Ci — Cio-Alkyl oder Ci- C10-. ' Aryl oder Heteroaryl, lineare und verzweigte Ci - Ci0-Alkyloxy oder Cj - Qo- Aryloxy, halogenierte lineare und verzweigte Q - Q0-Alkyl oder halogenierte Q - Qo-Aryl oder Heteroaryl, lineare und verzweigte Q - Ci0 Alkyl- oder Ci - Qo-Arylaminocarbonyl, lineare und verzweigte Q - Q0 Acyl, lineare und verzweigte Q - Q0 Dialkylamino, Q - Qo Arylamino, Q - Ci0 Diarylamino, Formyl, Oxo, Thio, Hydroxy, Carboxyl, Nitro, Cyano, Nitroso, und Halogene wie F, Cl, Br und I tragen können, und X ist ein Atom aus der Reihe C, S, P ist, das seinerseits weitere Substituenten aus der Reihe lineare und verzweigte Ci - C10-Alkyl oder C1- C10-Aryl oder Heteroaryl, lineare und verzweigte C1 - Q0- Alkyloxy oder C1 - C10-Aryloxy, halogenierte lineare und verzweigte C1 - Qo- Alkyl oder halogenierte C1 - C10- Aryl oder Heteroaryl, lineare und verzweigte C1 - C1O Alkyl- oder C1 - Q0-Arylammocarbonyl, lineare und verzweigte C1 - C10 Acyl, lineare und verzweigte C1 — C10 Dialkylamino, C1 - Cj0 Arylamino, C1 — C1O Oxo, Thio, Hydroxy, Carboxyl und Halogene wie F, Cl, Br und I tragen kann.HN R 3 where the substituents R 2 and R 3 are independently selectable from the series of heteroatoms from the series H, S, Si, N, O, Cl, Br, I, B, linear and branched C 1 -C 10 -alkyl or C 1 - C 10 aryl or heteroaryl, linear and branched C 1 - C 10 - vinyl or heteroaryl selected from pyridine, pyrimidine, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole , thiophene, furan, linear and branched C 1 - C 10 alkyloxy or C 1 - Qo-aryloxy, halogenated linear and branched Ci - Q 0 - alkyl, or halogenated C 1 - C O aryl or heteroaryl, linear and branched Ci - Ci 0 alkyl or C 1 - Qo-arylaminocarbonyl, linear and branched Ci - Ci 0 acyl, linear and branched C 1 - C 10 dialkylamino, C 1 - C 10 arylamino or together part of a cyclic C 1 - saturated or Q. unsaturated alkyl, aryl or heteroaryl moiety and are themselves further substituents from the series linear and branched Ci - Cio-alkyl or Ci- C 10 -. 'Is aryl or heteroaryl, linear and branched Ci - Ci 0 alkyloxy or Cj - q O- aryloxy, halogenated linear and branched Q - Q 0 alkyl or halogenated Q - Qo-aryl or heteroaryl, linear and branched Q - Ci 0 alkyl or Ci - Qo - arylaminocarbonyl, linear and branched Q - Q 0 acyl, linear and branched Q - Q 0 dialkylamino, Q - Qo arylamino, Q - Ci 0 diarylamino, formyl, oxo, thio, hydroxy, carboxyl, nitro, cyano, Nitroso, and halogens such as F, Cl, Br and I can carry, and X is an atom from the series C, S, P, which in turn further substituents from the series linear and branched Ci - C 10 -alkyl or C 1 -C 10 -aryl or heteroaryl, linear and branched C 1 -Q 0 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear and branched C 1 -Q-alkyl or halogenated C 1 -C 10 - aryl or heteroaryl, linear and branched C 1 - C 1O alkyl or C 1 - Q 0 -Arylammocarbonyl, and branched linear C 1 - C 10 acyl, linear and branched C 1 - C 10 dialkylamino, C 1 - C j 0 Arylamino, C 1 -C 10 oxo, thio, hydroxy, carboxyl and halogens such as F, Cl, Br and I. 11. Verfahren nach einem der Ansprüche 1-10 wobei das Alkin der allgemeinen Formel xx entspricht11. The method according to any one of claims 1-10 wherein the alkyne corresponds to the general formula xx R1 -= HR 1 - = H wobei der Substituent R1 wählbar ist aus der Reihe Heteroatome aus der Reihe S, Si, N, O, Cl, Br, I, B, lineare und verzweigte Ci - C10-Alkyl oder Ci- Cio-Aryl, Vinyl oder Heteroaryl aus der Reihe Pyridin, Pyrimidin, Pyridazin, Pyrazin, Triazin, Tetrazin, Pyrrol, Pyrazol, Isoxazol, Imidazol, Oxazol, Thiazol, Thiophen, Furan, lineare und verzweigte Ci - C10-Alkyloxy oder Ci - Qo- Aryloxy, halogenierte lineare und verzweigte C1 — Qo-Alkyl oder halogenierte C1 - Qo-Aryl oder Heteroaryl, lineare und verzweigte C1 - Qo Alkyl- oder C1 - Qo-Arylaminocarbonyl, lineare und verzweigte Q - C1O Acyl, lineare und verzweigte Ci - Qo -Dialkylamino, Q - Qo Arylamino und seinerseits weitere Substituenten aus der Reihe lineare und verzweigte C1 — Qo-Alkyl oder C1- Qo- Aryl oder Heteroaryl, lineare und verzweigte Q - Qo-Alkyloxy oder Ci - Qo- Aryloxy, halogenierte lineare und verzweigte C1 - Qo-Alkyl oder halogenierte C1 - Qo-Aryl oder Heteroaryl, lineare und verzweigte C1 - C10 Alkyl- oder C1 - Qo-Arylaminocarbonyl, lineare und verzweigte Q - C1O Acyl, lineare und verzweigte Ci - Q0 Dialkylamino, Ci - Ci0 Arylamino, Q - Ci0 Diarylamino, Formyl, Oxo, Thio, Hydroxy, Carboxyl, Nitro, Cyano, Nitroso, und Halogene wie F, Cl, Br und I tragen kann.wherein the substituent R 1 is selected from the series of heteroatoms from the series S, Si, N, O, Cl, Br, I, B, linear and branched Ci - C 10 -alkyl or Ci-Cio-aryl, vinyl or heteroaryl of the series pyridine, pyrimidine, pyridazine, pyrazine, triazine, tetrazine, pyrrole, pyrazole, isoxazole, imidazole, oxazole, thiazole, thiophene, furan, linear and branched C 1 -C 10 -alkyloxy or C 1 -C 8 -aryloxy, halogenated linear and branched C 1 -Qo-alkyl or halogenated C 1 -Qo-aryl or heteroaryl, linear and branched C 1 -Qo alkyl or C 1 -Qo-arylaminocarbonyl, linear and branched Q-C 10 -acyl, linear and branched C 1 -C 10 -Q- Dialkylamino, Q - Qo arylamino and in turn further substituents from the series linear and branched C 1 - Qo - alkyl or C 1 - Q - aryl or heteroaryl, linear and branched Q - Qo - alkyloxy or Ci - Qo - aryloxy, halogenated linear and branched C 1 --Qo-alkyl or halogenated C 1 --Qo-aryl or heteroaryl, linear and branched C 1 -C 10 -alk yl or C 1 - Qo-arylaminocarbonyl, linear and branched Q - C 1O acyl, linear and branched C - Q 0 dialkylamino, Ci - Ci 0 arylamino, Q - 0 Ci diarylamino, Formyl, oxo, thio, hydroxy, carboxyl, nitro, cyano, nitroso, and halogens such as F, Cl, Br and I. 12. Verfahren nach einem der Ansprüche 1-11, wobei eine Katalysatormenge von12. The method according to any one of claims 1-11, wherein a catalyst amount of 0,001 mol% bis 20 mol% bezogen auf das Stickstoffderivat eingesetzt wird.0.001 mol% to 20 mol% based on the nitrogen derivative is used. 13. Verfahren nach einem der Ansprüche 1-12, wobei die Reaktionstemperatur 50 °C bis 200 °C beträgt.13. The method according to any one of claims 1-12, wherein the reaction temperature is 50 ° C to 200 ° C. 14. Verfahren nach einem der Ansprüche 1-12, wobei die Reaktionstemperatur 80 °C bis 120 °C beträgt.14. The method according to any one of claims 1-12, wherein the reaction temperature is 80 ° C to 120 ° C. 15. Verfahren nach einem der Ansprüche 1 bis 14, wobei ein übliches Lösungsmittel eingesetzt wird. 15. The method according to any one of claims 1 to 14, wherein a conventional solvent is used.
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WO2007026654A1 (en) * 2005-08-29 2007-03-08 Kyoto University Enamide and process for producing the same, and dienamide and process for producing the same
WO2021122249A1 (en) 2019-12-20 2021-06-24 Basf Se Synthesis of n-vinyl compounds by reacting cylic nh-compounds with acetylene in presence of homogenous catalyst

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DE4333237A1 (en) * 1993-09-30 1995-04-06 Basf Ag Process for the preparation of N-vinyl compounds
DE19816479B4 (en) * 1998-04-14 2005-02-03 Müller, Thomas, Dr. Process for the preparation of enamines, imines, indoles and diamines from alkynes and their further processing by catalytic hydrogenation
DE19838666B4 (en) * 1998-08-26 2005-02-24 Müller, Thomas, Dr. Heterogeneous process for the preparation of enamines, imines, indoles and diamines from alkynes and further processing of the products obtained by catalytic hydrogenation
DE10001208B4 (en) * 2000-01-14 2005-02-03 Müller, Thomas, Dr. Process for the homogeneous catalytic hydroamination of alkynes for the production of enamines, imines, indoles and diamines and their further processing by catalytic hydrogenation

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007026654A1 (en) * 2005-08-29 2007-03-08 Kyoto University Enamide and process for producing the same, and dienamide and process for producing the same
WO2021122249A1 (en) 2019-12-20 2021-06-24 Basf Se Synthesis of n-vinyl compounds by reacting cylic nh-compounds with acetylene in presence of homogenous catalyst
CN114829339A (en) * 2019-12-20 2022-07-29 巴斯夫欧洲公司 Synthesis of N-vinyl compounds by reacting cyclic NH-compounds with acetylene in the presence of a homogeneous catalyst
JP2023508872A (en) * 2019-12-20 2023-03-06 ビーエーエスエフ ソシエタス・ヨーロピア Synthesis of N-Vinyl Compounds by Reaction of Cyclic NH Compounds with Acetylene in the Presence of Homogeneous Catalysts

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