[go: up one dir, main page]

WO2019162391A1 - Procédé de fabrication de composés aliphatiques hétérocycliques fluorés - Google Patents

Procédé de fabrication de composés aliphatiques hétérocycliques fluorés Download PDF

Info

Publication number
WO2019162391A1
WO2019162391A1 PCT/EP2019/054337 EP2019054337W WO2019162391A1 WO 2019162391 A1 WO2019162391 A1 WO 2019162391A1 EP 2019054337 W EP2019054337 W EP 2019054337W WO 2019162391 A1 WO2019162391 A1 WO 2019162391A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
ylene
group
diyl
hydrogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/EP2019/054337
Other languages
German (de)
English (en)
Inventor
Nairoukh ZACKARIA
Frank Glorius
Christoph SCHLEPPHORST
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Westfaelische Wilhelms Universitaet Muenster
Original Assignee
Westfaelische Wilhelms Universitaet Muenster
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Westfaelische Wilhelms Universitaet Muenster filed Critical Westfaelische Wilhelms Universitaet Muenster
Publication of WO2019162391A1 publication Critical patent/WO2019162391A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—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 no 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
    • C07D211/38—Halogen atoms or nitro radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B53/00—Asymmetric syntheses
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/003—Compounds containing elements of Groups 3 or 13 of the Periodic Table without C-Metal linkages
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
    • C07F7/1804—Compounds having Si-O-C linkages

Definitions

  • the present invention relates to the field of fluorinated heterocyclic aliphatic compounds.
  • Such compounds play a major role in the pharmaceutical or agrochemical field due to the polarity of the C-F bond with concomitant steric similarity to C-H bonds and other effects.
  • additive dipole effects in several identically aligned C-F bonds are of interest for materials chemistry applications.
  • a process for producing fluorinated heterocyclic aliphatic compounds comprising the step of hydrogenating a heteroaromatic fluorochemical precursor substance with a catalyst comprising at least one
  • the r / .v product is preferably produced in many applications, which allows access to sterically defined products.
  • aromatic fluorine-containing substance is understood to mean, in particular, fluorinated heterocyclic 5-or 6-membered rings with p-electron sequestrates and fluorinated annelated heteroaromatic multi-cycles.
  • aromatic fluorine-containing substance is understood to mean, in particular, that at least one fluorine is present as a substituent on an aromatic ring.
  • aromatic fluorine-containing precursors containing one or more benzo-fused heteroaromatic rings.
  • hydrogenation is understood in particular to mean that in the sum of two hydrogens are added to a "double bond" of the aromatic compound.
  • present invention is not limited to hydrogen as a concrete reducing agent although this (as described below) is a preferred
  • the catalyst comprises rhodium with at least one labile ligand, preferably more than one labile ligand.
  • Preferred labile ligands are alkenes, cyclic bisalkenes, halides, triflates, acetonitrile, weakly coordinating anions such as tetrafluoroborate or phosphines.
  • alkenes especially cyclic dialkene such as cyclooctadiene or bicyclo [2.2. l] hepta-2,5-diene.
  • Preferred catalysts according to a preferred embodiment of the invention are cyclooctadiene rhodium chloride dimer ([Rh (COD) Cl] 2 ), bis (l, 5-cyclooctadiene) rhodium (I) tetrafluoroborate, bis (acetonitrile) (l, 5-cyclooctadiene) rhodium (I) tetrafluoroborate
  • Tris (tricyclohexylphosphine) rhodium (I) chloride [Rh (PCys sCl]
  • the catalyst comprises at least one N-heterocyclic carbene ligand.
  • the catalyst does not comprise an N-heterocyclic carbene ligand.
  • N-heterocyclic carbene ligand is understood to mean electron-rich, nucleophilic compounds of divalent carbon species with electron sequets, such as, for example, Pyrrolidinylidenes, pyrrolidens, imidazolylidenes, imidazolidinylidenes, piperidinylenes, hexahydropyrimidinylenes and triazolylidenes. Particularly preferred are
  • Pyrrolidinylidenes pyrrolidens, imidazolylidenes and imidazolidinylidenes, more preferably pyrrolidinylidenes.
  • the N-heterocyclic carbene ligand comprises a pyrrolidinylidene compound
  • the catalyst is used in substance.
  • the process according to the invention comprises two steps: a) in situ synthesis of the catalyst used in step b) from suitable precursors b) carrying out the hydrogenation as described above and in the following
  • a suitable rhodium-containing precursor is in particular the
  • step a) is carried out by reacting a suitable salt of the N-heterocyclic carbene with a strong base, preferably selected from NaOtBu, LDA, KOtBu, NaH, KHMDS, LiHMDS with a rhodium-forming precursor, for example [Rh (COD) Cl] 2 , If necessary, reacted at elevated temperature.
  • a strong base preferably selected from NaOtBu, LDA, KOtBu, NaH, KHMDS, LiHMDS
  • a rhodium-forming precursor for example [Rh (COD) Cl] 2
  • Halides, pseudohalides such as oxygen-containing anions, in particular triflates and weak can be used as anions coordinating anions such as tetrafluoroborate, hexafluoroantimonate or
  • Hexafluorophosphate serve.
  • Preferred solvents here are hexane, diethyl ether or tetrahydrofuran.
  • step b) If, in step b), a different solvent is used than in step a), the solvent is then optionally removed between the two steps.
  • the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:
  • R 1 to R 5 independently of one another are alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene,
  • R 6 and R 7 independently of one another are hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl,
  • Heterocycloalkylenes heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl,
  • Haloalkyl, silylalkyl, silylalkyloxy, where, with suitable radicals, one or more non-adjacent CH 2 groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -S0 2 -, -S CO-, -CO-S-, -CY ⁇ CY 2 or -C C- may be replaced such that O and / or S atoms are not directly connected to one another, likewise optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH3 groups are understood as CH 2 groups in the sense of CH 2 - H .) And R 1 to R 7 may be substituted so that optionally between R 2 and R 3 , R 4 and R 3 , R 6 and R 7 , R 1 and R 4
  • alkyl linear and branched C 1 -C 8 -alkyls
  • long-chain alkyls linear and branched C 5 -C 20 -alkyls
  • alkenyl C 2 -C 6 -alkenyl
  • cycloalkyl C 3 -C 8 -cycloalkyl
  • alkoxy C 1 -C 6 -alkoxy
  • long-chain alkoxy linear and branched C5-C20 alkoxyalkylenes: selected from the group comprising:
  • aryl selected from aromatics having a molecular weight below 300Da arylenes: selected from the group consisting of: 1,2-phenylenes; 1,3-phenylenes; 1,4-phenylenes; l, 2-naphtalenylene; l, 3-naphtalenylene; 1,4-naphthalenylenes; 2,3-naphtalenylene; l-hydroxy-2,3-phenylene; 1-hydroxy-2,4-phenylene; 1-hydroxy-2,5-phenylene; and 1-hydroxy-2,6-phenylene, heteroaryl: selected from the group consisting of: pyridinyl; pyrimidinyl; pyrazinyl; triazolyl; pyridazinyl; l, 3,5-triazinyl; chinoninyl; isochinoninyl; quinoxalin
  • heteroarylenes selected from the group comprising: pyridinediyl; quinolindiyl; pyrazodiyl; pyrazoldiyl; triazolediyl; pyrazinediyl, thiophenediyl; and imidazolediyl, where the
  • heteroarylenes as a bridge in the compound of any atom in the ring of the
  • heteroaryl especially preferred are: pyridine-2, 3-diyl; pyridine-2, 4-diyl; pyridine-2, 5-diyl; pyridine-2, 6-diyl; pyridine-3,4-diyl; pyridine-3,5-diyl; quinoline-2, 3-diyl; quinolin-2,4-diyl; quinoline-2, 8-diyl; isoquinoline-1,3-diyl; isoquinoline-l, 4-diyl; pyrazole-1,3-diyl; pyrazole-3,5-diyl; triazole-3,5-diyl; triazole-1,3-diyl; pyrazin-2,5-diyl; and imidazole 2,4-diyl, thiophene-2,5-diyl, thiophene-3,5-diyl; a -CC-C6 heterocycloalky
  • heterocycloalkylenes selected from the group comprising: piperidin-1,2-ylene; piperidine-2,6-ylene; piperidin-4,4-ylidene; l, 4-piperazin-l, 4-ylene; l, 4-piperazin-2,3-ylene; 1,4-piperazine-2,5-ylene; l, 4-piperazin-2,6-ylene; l, 4-piperazin-1, 2-ylene; 1, 4-piperazine-1, 3-ylene; l, 4-piperazin-l, 4-ylene; tetrahydrothiophen-2,5-ylene; tetrahydrothiophen-3,4-ylene; tetrahydrothiophen-2,3-ylene; tetrahydrofuran-2,5-ylene; tetrahydrofuran-3,4-ylene;
  • tetrahydrofuran-2,3-ylene pyrrolidin-2,5-ylene; pyrrolidine-3, 4-ylene; pyrrolidin-2,3-ylene; pyrrolidin-1,2-ylene; pyrrolidin-1, 3-ylene; pyrrolidin-2,2-ylidene; l, 4,7-triazacyclonon-1, 4-ylene; 1,4,7-triazacyclonon-2,3-ylene; l, 4,7-triazacyclonon-2,9-ylene; l, 4,7-triazacyclonon-3,8-ylene; 1, 4,7-triazacyclonon-2,2-ylidenes; 1, 4,8, 1-tetraazacyclotetradec-1,4-ylene;
  • Heterocycloalkyls may be connected.
  • amine the group -N (R) 2 wherein each R is independently selected from: hydrogen; C1-C6-alkyl; Cl-C6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring.
  • halogen selected from the group consisting of: F; Cl; Br and I
  • haloalkyl selected from the group consisting of mono-, di-, tri-, poly- and perhalogenated linear and branched C 1 -C 8 -alkyl pseudohalogen: selected from the group consisting of -CN, -SCN, -OCN, N 3, -CNO, -SeCN sulphonate: the group -S (O) 20R, wherein R is selected from: hydrogen; Cl-C6-alkyl; phenyl; Cl-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca, sulphate: the group -0S (0) 20R, where R is selected from: hydrogen; Cl-C6-alkyl; phenyl; Cl-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca, sulphone: the group -S (O
  • carboxylate the group -C (O) OR, where R is selected from: hydrogen; Cl-C6-alkyl; phenyl; Cl-C6-alkyl-C6H5; Li; N / A; K; Cs; mg; and Ca, carbonyl: the group -C (O) R, wherein R is selected from: hydrogen; Cl-C6-alkyl;
  • phosphines the group -P (R) 2, wherein each R is independently selected from: hydrogen; Cl-C6-alkyl; phenyl; and C1-C6-alkyl-C6H5, phosphine oxide: the group -P (O) R2, wherein R is independently selected from: hydrogen; Cl-C6-alkyl; phenyl; and C 1 -C 6 -alkyl-C 6 H 5; and amines (to give phosphonamidate) selected from the group: -NR'2, where each R 'is independently selected from:
  • polyethers selected from the group consisting of - (0-CH 2 -CH (R)) n -0H and - (0-CH 2 - CH (R)) n -H wherein R is independently selected from: hydrogen, alkyl, aryl , halogen and n is from 1 to 250 silylalkyl: the group -S1R3 wherein each R is independently selected from: hydrogen; C1-C6-alkyl; phenyl; Cl-C6-alkyl-C6H5 and amine (to give sulphonamide) selected from the group: -NR'2, where each R 'is independently selected from:
  • sulphonamides selected from the group: -NR'2, where each R 'is independently selected from: hydrogen; Cl-C6-alkyl; CLC6-alkyl-C6H5; and phenyl, wherein when both R 'are C1-C6 alkyl, both R' can form a -NC3 to NC5 heterocyclic ring wherein the remaining alkyl chain forms an alkyl substituent on the heterocyclic ring
  • alkyl linear and branched C 1 -C 6 -alkyl
  • long-chain alkyls linear and branched C5-C10 alkyl, preferably C6-C8 alkyls
  • alkenyl C3-C6 alkenyl
  • cycloalkyl C6-C8-cycloalkyl
  • alkoxy C1-C4 alkoxy
  • long-chain alkoxy linear and branched C5-C10 alkoxy
  • preferably linear C 6 -C 8 alkoxyalkylenes selected from the group comprising: methylenes; l, 2-ethylene; l, 3-propylene; butan-2-ol-l, 4-diyl; l, 4-butylene; cyclohexane-l, l-diyl; cyclohexane-l, 2-diyl; cyclohexane-1, 4-diyl
  • heteroaryl may be linked to the compound via any atom in the ring of the selected heteroaryl, heteroarylenes: selected from the group comprising: pyridine, 2,3-diyl; pyridin-2,4-diyl; pyridin-2,6-diyl; pyridine-3,5-diyl; quinolin-2,3-diyl; quinolin-2,4-diyl; isoquinoline-l, 3-diyl; isoquinoline-l, 4-diyl; pyrazol-3,5-diyl; and imidazole-2,4-diyl, heterocycloalkyl: selected from the group comprising:
  • heteroaryl may be linked to the compound via any atom in the ring of the selected heteroaryl heterocycloalkylene: selected from the group comprising:
  • Heterocycloalkyl may be joined to the compound via any atom in the ring of the selected heterocycloalkyl amine: the group -N (R) 2, wherein each R is independently selected from: hydrogen; Cl-C6-alkyl; and benzyl, halogen: selected from the group consisting of: F and Cl, sulphonates: the group -S (O) 20R, wherein R is selected from: hydrogen; Cl-C6-alkyl;
  • N / A; K; mg; and Ca sulphate: the group -0S (0) 20R, wherein R is selected from: hydrogen; Cl-C6-alkyl; N / A; K; mg; and Ca, sulphone: the group -S (O) 2R, wherein R is selected from: hydrogen; C1-C6-alkyl;
  • each R ' is independently selected from: hydrogen; Cl-C6-alkyl; and benzyl, carboxylate: the group -C (O) OR wherein R is selected from hydrogen; N / A; K; mg; Ca; Cl-C6-alkyl; and benzyl, carbonyl: the group: -C (O) R, wherein R is selected from: hydrogen; Cl-C6-alkyl; benzyl and amines selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; Cl-C6-alkyl; and benzyl, phosphonates: the group -P (O) (OR) 2, wherein each R is independently selected from:
  • phosphines the group -P (R) 2, wherein each R is independently selected from: hydrogen; Cl-C6-alkyl; and benzyl, phosphine oxide: the group -P (O) R2, wherein R is independently selected from: hydrogen; Cl-C6-alkyl; benzyl and amines selected from the group: -NR'2, wherein each R 'is independently selected from: hydrogen; Cl-C6-alkyl; and benzyl.
  • polyethers selected from the group Eisend- (0-CH 2 -CH (R)) n -OH and - (0-CH 2 - CH (R)) n -H wherein R is independently selected from: hydrogen, methyl, halogen and n is from 5 to 50, preferably 10 to 25.
  • R is independently selected from: hydrogen, methyl, halogen and n is from 5 to 50, preferably 10 to 25.
  • the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:
  • R 1 to R 3 independently of one another are alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene,
  • R 4 to R 7 independently of one another are hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl,
  • Heterocycloalkylenes heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl,
  • Haloalkyl, silylalkyl, silylalkyloxy, where, with suitable radicals, one or more non-adjacent CH 2 groups independently of one another by -O-, -S-, -NH-, -NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -S0 2 -, -S CO-, -CO-S-, -CY ⁇ CY 2 or -C C- may be replaced such that O and / or S atoms are not directly connected to one another, likewise optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH3 groups are understood as CH 2 groups in the sense of CH 2 - H .) And R 1 to R 7 may be substituted so that optionally between R 2 and R 3 , R 1 and R 2 / R 3 or R 2 / R 3 and R 7
  • the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:
  • R 1 or R 2 may be either a substituted or unsubstituted carbon or a nitrogen (but R 1 and R 2 are not both nitrogen), where the substitutions are selected from (independently of one another) alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, Cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl,
  • Heterocycloalkylenes heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl,
  • Halo-ketoalkyl, silylalkyl, silylalkyloxy, where suitable radicals include one or more non-adjacent CH 2 groups independently of one another by -O-, -S-, -NH-, - NR ° -, -SiR ° R °° -, -CO-, -COO-, -OCO-, -OCO-O-, -S0 2 -, -S CO-, -CO-S-, -CY ⁇ CY 2 or - C C- may be replaced such that O and / or S atoms are not directly connected to one another, likewise optionally with aryl or heteroaryl preferably containing 1 to 30 C atoms are replaced (terminal CH3 groups are understood as CH 2 groups in the sense of CH 2 - H .)
  • R 3 and R 4 are each independently alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, heteroaryl, heterocycloalkylene,
  • the bond between R 1 and R 2 may be a single or double bond and R 1 and R 3 on the one hand and / or R 2 and R 4 on the other hand may be substituted so that between R 1 and R 3 or
  • the catalyst comprises an N-heterocyclic carbene ligand of the following structure:
  • R 3 and R 4 are defined as in the previous catalyst, R 5 and R 6 are independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy,
  • the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:
  • R 3 , R 4 and R 5 are defined as in the previous catalyst.
  • the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:
  • R 1 or R 2 may be either a substituted or unsubstituted carbon or a nitrogen (but where R 1 and R 2 are not both nitrogen)
  • R 1 and R 2 may be a single or double bond
  • R 7 , R 8 , R 9 and R 10 are independently hydrogen, alkyl, long-chain alkyl, alkoxy, long-chain alkoxy, cycloalkyl, haloalkyl, aryl, haloaryl, Heteroaryl, heterocycloalkylene, heterocycloalkyl, haloheteroaryl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, ketoaryl, haloketoaryl, ketoheteroaryl, ketoalkyl,
  • the catalyst comprises at least one N-heterocyclic carbene ligand of the following structure:
  • R 7 and R 9 are defined as in the previous catalyst and Xi and X 2 can independently be O, NH or CH 2 .
  • the catalyst comprises at least one further ligand on rhodium, preference being given to labile ligands.
  • ligands whose bonding to the rhodium is so weak that, if appropriate, they are at least temporarily not bound to the rhodium in the course of the reaction.
  • Preferred such labile ligands are dialkens, preferably COD, or norbornadiene, or alternatively to dialkenene, two ethylenes. Further possible ligands are
  • the amount of catalyst before the beginning of the reaction is preferably from> 0.001 mol% to ⁇ 10 mol% (based on the aromatic precursor substance at the beginning of the reaction) preferably> 0.05 mol% to ⁇ 5 mol%, more preferably> 0.1 mol% to ⁇ 3 mol%, and most preferably> 0.2 mol% to ⁇ 1 mol%. It has been found that even with these relatively small amounts of catalyst, nevertheless, the reaction can often be carried out in high yield.
  • the process is carried out in an organic solvent, have proven particularly useful in practice (and are therefore preferred): methanol, THF, 2-methyl-THF, l, 4-dioxane or mixtures of these solvents. Particularly preferred are THF and 2-methyl-THF.
  • the process is preferably carried out at a temperature of> 0 ° C.
  • the upper limit is basically limited only by the boiling point of the solvent used. Even more preferred are temperatures from> 10 ° C to ⁇ 50 ° C, most preferred
  • the preferred H 2 pressure (at the beginning of the reaction)> 3 bar, more preferably ranges from> 10 bar to ⁇ 150 bar.
  • the reaction is preferably carried out for a reaction time of> 3h to ⁇ 2d, particularly preferred reaction times are> 5h to ⁇ 30h.
  • the reaction is carried out in the presence of an additive selected from the group boranes and silanes. It has been found that so often the yield can be increased even further.
  • the additive is preferably used in a ratio to the precursor substance of> 0.1: 1 to ⁇ 10: 1 (mokmol), preferably> 1: 1 to ⁇ 4: 1 (mokmol).
  • the additive is either a borane or a silane, with boranes being preferred.
  • Preferred boranes are dialkylborohydrides and / or dioxaborolanes, where
  • Dioxaborolanes are preferred.
  • the additive is selected from the group containing pinacolborane (4,4,5,5-tetramethyl-l, 3,2-dioxaborolane), catecholborane, 9-BBN.
  • Preferred silanes are silanes of the structure R 1 R 2 SiH 2 , where R 1 and R 2 are selected independently of one another from alkyl or aryl.
  • R 1 is preferably alkyl and R 2 is aryl.
  • the reaction is carried out in the presence of a Lewis acid, preferably a Lewis acid, which has dehydrating properties. It has been found that so often the yield can be increased even further.
  • a Lewis acid preferably a Lewis acid, which has dehydrating properties. It has been found that so often the yield can be increased even further.
  • Preferred additives are selected from the group comprising molecular sieve, preferably molecular sieve 4 A and 3 A,
  • the ratio of additive to educt (before the reaction) of from> 10 to ⁇ 200 mg per 1 mmol of starting material is preferred
  • a reaction-dried oven at 135 ° C (depending on the amount of solvent used either a 9 mL screw-cap vial (to 4 mL) or a 50 mL glass cylinder) filled with magnetic stirrer was allowed to cool under vacuum and washed with powdered activated 4 A molecular sieve (50 mg) catalyst ( 0.50 to 3.0 mol%) and solid starting material (1.0 mmol) - if the educt used is solid - filled in air.
  • the atmosphere in the vial was exchanged with argon via a septum (3 x vacuum / argon cycle). After addition of tetrahydrofuran (1 mL, 1 M) and then gg.
  • Liquid, over calcium hydride distilled starting material (1.0 mmol) - if the reactant used is liquid - and 4,4,5,5-tetramethyl-l, 3, 2-dioxaborolane (HBpin, 2.0-0.4.0 mmol, 2.0-4.0 equiv.) was transferred under argon to the vessel under argon atmosphere in a 150 mL steel autoclave under argon atmosphere, during which the autoclave cap was opened and the Autoclave was held under an inert gas by means of an argon-flowed hose.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne un nouveau procédé de fabrication de composés aliphatiques hétérocycliques fluorés à partir des composés aromatiques analogues par hydrogénation avec un système catalytique à base de Rh.
PCT/EP2019/054337 2018-02-23 2019-02-21 Procédé de fabrication de composés aliphatiques hétérocycliques fluorés Ceased WO2019162391A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE102018104201.9A DE102018104201A1 (de) 2018-02-23 2018-02-23 Verfahren zur Herstellung fluorierten heterocyclischen aliphatischer Verbindungen
DE102018104201.9 2018-02-23

Publications (1)

Publication Number Publication Date
WO2019162391A1 true WO2019162391A1 (fr) 2019-08-29

Family

ID=65598611

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2019/054337 Ceased WO2019162391A1 (fr) 2018-02-23 2019-02-21 Procédé de fabrication de composés aliphatiques hétérocycliques fluorés

Country Status (2)

Country Link
DE (1) DE102018104201A1 (fr)
WO (1) WO2019162391A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024108774A1 (fr) * 2022-11-22 2024-05-30 Guangdong Technion-Israel Institute Of Technology Hydroboration double catalysée par un métal d'hétérocycles d'azote

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007071358A1 (fr) * 2005-12-20 2007-06-28 Novartis Ag Dérivés d'acide nicotinique en tant que modulateurs des récepteurs métabotropiques du glutamate
WO2013053796A1 (fr) * 2011-10-13 2013-04-18 Westfälische Wilhelms Universität Münster Procédé d'hydrogénation catalytique d'hétéroaromates

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007071358A1 (fr) * 2005-12-20 2007-06-28 Novartis Ag Dérivés d'acide nicotinique en tant que modulateurs des récepteurs métabotropiques du glutamate
WO2013053796A1 (fr) * 2011-10-13 2013-04-18 Westfälische Wilhelms Universität Münster Procédé d'hydrogénation catalytique d'hétéroaromates

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
MARIO P. WIESENFELDT ET AL: "Hydrogenation of fluoroarenes: Direct access to all- cis -(multi)fluorinated cycloalkanes", SCIENCE, vol. 357, no. 6354, 1 September 2017 (2017-09-01), US, pages 908 - 912, XP055577500, ISSN: 0036-8075, DOI: 10.1126/science.aao0270 *
MARIO P. WIESENFELDT ET AL: "Supplementary Materials for Hydrogenation of fluoroarenes: Direct access to all- cis -(multi)fluorinated cycloalkanes", SCIENCE, vol. 357, no. 6354, 10 August 2017 (2017-08-10), US, pages 1 - 132, XP055576365, ISSN: 0036-8075, DOI: 10.1126/science.aao0270 *
MU-WANG CHEN ET AL: "Asymmetric Hydrogenation of Isoquinolines and Pyridines Using Hydrogen Halide Generated in Situ as Activator", ORGANIC LETTERS, vol. 19, no. 18, 7 September 2017 (2017-09-07), US, pages 4988 - 4991, XP055577788, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.7b02502 *
RAN-NING GUO ET AL: "An efficient route to chiral N-heterocycles bearing a C-F stereogenic center via asymmetric hydrogenation of fluorinated isoquinolines", CHEMICAL COMMUNICATIONS, vol. 49, no. 76, 1 January 2013 (2013-01-01), pages 8537 - 8539, XP055577545, ISSN: 1359-7345, DOI: 10.1039/c3cc45341c *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024108774A1 (fr) * 2022-11-22 2024-05-30 Guangdong Technion-Israel Institute Of Technology Hydroboration double catalysée par un métal d'hétérocycles d'azote

Also Published As

Publication number Publication date
DE102018104201A1 (de) 2019-08-29

Similar Documents

Publication Publication Date Title
EP2838872B1 (fr) Procédé de fabrication d'alcools ramifiés
EP3994117B1 (fr) Hydrogénation d'esters en vue d'obtenir des alcools en présence d'un complexe de ru-pnn
EP2167565A1 (fr) Procédé de synthèse d'oligo/polythiophènes selon un procédé de synthèse monotope
Field et al. Protonation and rearrangement of bis (acetylide) complexes of iron: formation of coordinated. eta. 3-butenynes
DE2221113A1 (de) Katalytisches Verfahren zum Isomerisieren von 2-Methyl-3-butennitril zu linearen Pentennitrilen
EP3601203B1 (fr) Procédé de fabrication de composés aliphatiques cycliques fluorés
Al-Shboul et al. Catalytic synthesis of vinylphosphanes via calcium-mediated intermolecular hydrophosphanylation of alkynes and butadiynes
WO2019162391A1 (fr) Procédé de fabrication de composés aliphatiques hétérocycliques fluorés
EP1322583B1 (fr) Procede d'isomerisation d'alcools allyliques
CN111099982B (zh) 3-羟基丙醛的合成方法
EP2865446A1 (fr) Procédé de production d'alcool secondaire optiquement actif
EP2535344A1 (fr) Liaisons substituées par silsesquioxanes, leur procédé de fabrication, leur utilisation comme ligands pour systèmes catalytiques et systèmes catalytiques
Bleeke et al. Pentadienyl-metal-phosphine chemistry. 5. The reaction chemistry of (. eta. 5-2, 4-dimethylpentadienyl) bis (trimethylphosphine) cobalt
EP0437690B1 (fr) Procédé pour l'hydrogénation asymétrique de dérivés alpha-cétocarbonyliques en dérivés alpha-hydroxycarbonyliques optiquement actifs
DE102011054477A1 (de) Verfahren zur katalytischen Heteroaromatenhydrierung
DE102004006422A1 (de) Heterocyclische Carbenkomplexe und deren Anwendungen
DE2018054C3 (de) Verfahren zur Herstellung von Octadienol
WO2007017453A1 (fr) Procede de production d'alcools heteroaromatiques
DE10010046A1 (de) Verfahren zur Herstellung von Aminen und neue Amine
WO2020058505A1 (fr) Isomérisation d'alcènes
DE4101737A1 (de) Verfahren zur herstellung von olefinischen verbindungen aus carbonyl-verbindungen und diazoalkanen
Plantevin et al. Insertion of NH into the rhenium carbon bonds of a Fischer-type rhenacyclobutadiene. Preparation and characterization of azarhenacyclic complexes
EP1628985A2 (fr) Ligands chiraux et leurs complexes de metaux de transition
EP4180440A1 (fr) Biarylphosphines cycliques comme ligands pour catalyseurs contenant du palladium dans les réactions de couplage croisé
DE4414328A1 (de) Besonders vorteilhaftes Verfahren zur Herstellung von cyclischen Olefinen

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 19708040

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 19708040

Country of ref document: EP

Kind code of ref document: A1