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WO1998027051A2 - Amidohydroxylation asymetrique catalytique d'olefines au moyen de n-halo carboxamides - Google Patents

Amidohydroxylation asymetrique catalytique d'olefines au moyen de n-halo carboxamides Download PDF

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WO1998027051A2
WO1998027051A2 PCT/US1997/023511 US9723511W WO9827051A2 WO 1998027051 A2 WO1998027051 A2 WO 1998027051A2 US 9723511 W US9723511 W US 9723511W WO 9827051 A2 WO9827051 A2 WO 9827051A2
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asymmetric
iodo
bromo
amide
product
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WO1998027051A3 (fr
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K. Barry Sharpless
Milan Bruncko
Gunther Schlingloff
Rodney Guy
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Scripps Research Institute
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/16—Preparation of optical isomers
    • C07C231/18—Preparation of optical isomers by stereospecific synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

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  • the invention relates to the regio-selective and enantio- selective conversion of olefins to ⁇ -hydroxyamides. More particularly, the invention relates to catalytic asymmetric additions or amidohydroxylations of olefins and other unsaturated substrates using an N-halo carboxamide as an oxidizing agent in the presence of an osmium catalyst and a chiral ligand.
  • the ⁇ -aminoalcohol moiety is one of the most abundant structural units in biologically active compounds.
  • Recent developments by us Li et al. Angew. Chem. 1996, 208, 449-452; Angew. Chem. Int. Ed. Engl. 1996, 35, 451-454; Li et al. Acta Chem. Scand. 1996, 50, 649-651) and others (Larrow et al. J. Am. Chem. Soc. 1996, 118, 7420-7421; Shibasaki et al. Pure Appl. Chem. 1996, 68, 523-530) have led to viable metal catalyzed routes for its asymmetric synthesis.
  • Each oxyamination procedure has unique reaction conditions and includes variations in solvents, auxiliary salts, nucleophiles, temperature, stoichiometric v. catalytic amounts of osmium species and stoichiometric v. catalytic amounts of ligand.
  • Each procedure is highly dependent on the nature of the substrate and possesses unique properties which afford different yields, chemoselectivities, stereoselectivities, regioselectivities and enantioselectivitive outcomes.
  • the first reported oxyamination procedure (Sharpless et al. J. Am . Chem . Soc . 1975, 97 , 2305) generated aminoalcohols from mono and di substituted olefins, using stoichiometric quantities of a tri-oxo(tert-butylimido) osmium species.
  • the procedure required reductive cleavage of the osmate ester which was performed with lithium aluminum hydride and afforded tertiary vicinal aminoalcohols. Yields were good to excellent, but in some cases, the side product vicinal diol was formed as an undesired by-product.
  • the in situ procedure for generating the chloramine salts, involved stirring a suspension of the arylsulfonamide with an equivalent of sodium hypochlorite (Clorox) until a homogenous solution was obtained.
  • the yields were comparable with those obtained with isolated chloramine salts and the procedure was found most effective for monosubstituted and 1,2 disubstituted olefins.
  • the phase transfer method gave poor results with trisubstituted and 1, 1-disubstituted olefins and the procedure did not succeed with diethyl fumarate and 2- cyclohexen-1-one. Sharpless et al. J. Org. Chem .1978, 43, 2544.
  • phase transfer catalyst or tert-butyl alcohol procedures succeeded with tetramethyl ethylene, 2 , 3-dimethyl-2- octene, diethyl fu arate, or 2-cyclohexen-l-one. Negative results were also obtained with most hindered tri- and tetrasubstituted olefins. Herranz E. , MIT Ph.D. Thesis, 1979, 33.
  • Solvent conditions for the synthesis of the hydroxysulfonamides included organic solvents such as acetonitrile, tert-butyl alcohol, isopropyl alcohol and chloroform which was in contact with the aqueous phase in the phase transfer catalyst procedure.
  • Preferred ligands for use with sulfonamides have included the use of monovalent cinchona alkaloids or the bivalent phthalazine based, commercially available (DHQ) 2 PHAL and (DHQD) 2 PHAL alkaloids. Sharpless et al. Angew. Chemie Intl Ed . 1996, 35 , 451.
  • Temperature conditions for the hydroxysulfonamide asymmetric aminohydroxylations have varied from 60 C C to 25 °C for reactions including sulfonamides, auxiliary salts, ligands, phase transfer catalysts and stoichiometric or catalytic osmium species, primarily in organic solvents with small amounts of water. Recently, it has been shown that temperature can been lowered to 0 °C while running the reaction, to obtain product by filtration; many hydroxysulfonamides tend to be highly crystalline Sharpless et al. Acta Chemica Scandinavica 1996 in press.
  • nucleophiles such as tetraethylammonium acetate were also proven to be beneficial to the reaction in the procedures using the silver and mercury salts of the chloramines from carbonates.
  • the reactivity and yields were enhanced by addition of excess AgN0 3 and Hg(N0 3 ) 2 (over that needed to react with the NaClNCOOR salt) Sharpless et al. J . Org Chem . 1980, 45 , 2710.
  • Preferred conditions included employment of ROCONClNa + Hg(N0 3 ) 2 + Et 4 NOAc with N-chloro-N-sodiocarbamates; these conditions were recommended as the best procedure for mono, di and tri substituted olefins even including some olefins unreactive in all of the various chloramine T based processes. (Sharpless et al. Org. Syn . 1981, 61 , 93) .
  • Sharpless disclosed the use of stoiciometric amounts of a first generation monovalent alkaloid ligand with a tert-butyl derived N-chloro-N-argentocarbamate for hydroxyamination in a series of patent applications directed to ligand accelerated catalytic asymmetric dihydroxylation.
  • the invention is directed to a method for converting olefinic substrates to asymmetric ⁇ -hydroxyamide products.
  • the method of the invention employs an asymmetric addition reaction involving the addition of a carboxamide radical and a hydroxyl radical to the olefinic substrate.
  • Enhanced yields, regioselectivity, and enantioselectivity may be achieved according to the method of the invention.
  • the asymmetric addition reaction is carried out in a reaction solution which includes the olefinic substrate, an osmium catalyst, a chiral ligand for enantio erically and regioselectively directing the asymmetric addition, an N-halo carboxamide, a base, and a solvent in homogeneous or heterogeneous conditions.
  • the N-halo carboxamide serves as a source for the carboxamide radical.
  • the olefinic substrate and N-halo carboxamide are present and soluble within the solvent or cosolvent in approximately stoichiometric amounts as defined below.
  • the osmium is present within the solvent or co-solvent in catalytic amounts.
  • One aspect of the invention is directed to a method for converting an olefinic substrate to an asymmetric amidoalcohol product by means of a one step osmium-catalyzed asymmetric addition.
  • a carboxamide radical and a hydroxyl radical are added to the olefinic substrate.
  • the reaction mixture employs a solvent having both an organic component and an aqueous component.
  • the aqueous component of the solvent serves as the source of the hydroxyl radical.
  • An N- halo carboxamide serves as the source of the carboxamide radical.
  • the reaction mixture also includes the olefinic substrate, the N-halo carboxamide, an osmium-containing catalyst, a chiral ligand for enantiomerically directing said asymmetric addition, and a base.
  • N-halo carboxamides include N-fluoro- ⁇ - C 15 (alkyl) ) -amide, N-chloro- (C 1 -C 15 (alkyl) ) -amide, N-bromo-(C !
  • N-halo carboxamides are N-bromoacetamide, N-chloroacetamide, N- bromobenzamide, N-chlorobenzamide, N-fluoro-2-chloro-acetamide, N-fluoro-2-bromo-acetamide, N-fluoro-2-iodo-acetamide, N-bromo- 2-chloro-acetamide, N-bromo-2-bromo-acetamide, N-bromo-2-iodo- acetamide, N-iodo-2-chloro-acetamide, N-iodo-2-bromo-acetamide, N-iodo-2-iodo-acetamide, N-chloro-p-methoxy benzamide, N-chloro- 2-methoxy acetamide, N-bromo-p-methoxy acetamide, N-bromo-2- methoxy acetamide, N-iododo
  • Preferred osmium containing catalysts include potassium osmate dihydrate, osmium tetroxide, osmium(IV) oxide, osmium(IV) oxide dihydrate, osmium(III) chloride, and osmium hexachlorooxmate(IV) .
  • the catalytic concentration of the osmium is within a range of 0.50 - 20 mole%.
  • Preferred chiral ligands include p-phenylbenzoyl dihydroquinidine; acetyl dihydroquinine; dimethylcarbamoyl dihydroquinine; benzoyl dihydroquinine; 4-methoxybenzoyl dihydroquinine; 4-chlorobenzoyl dihydroquinine; 2-chlorobenzoyl dihydroquinine; 4-nitrobenzoyl dihydroquinine; 3-chlorobenzoyl dihydroquinine; 2-methoxybenzoyl dihydroquinine; 3- methoxybenzoyl dihydroquinine; 2-naphthoyl dihydroquinine; cyclohexanoyl dihydraquinine; p-phenylbenzoyl dihydroquinine; methoxydihydroquinidine; acetyl dihydroquinidine; dimethylcarbamoyl dihydroquinine
  • R x is radical selected from a group consisting of a group represented by one of the following structures:
  • the chiral ligand is present and soluble within the reaction solution at a catalytic concentration within a range of substantially 0.50 mole % to 10 mole %.
  • the catalytic concentration of the osmium is within a range of 0.50 - 20 mole% and the chiral ligand has a catalytic concentration of approximately 5 mole%.
  • Preferred bases include LiOH, NaOH, KOH, NH 4 OH, Na 2 C0 3 , K 2 C0 3 , CaC0 3 , and BaC0 3 .
  • preferred organic compounds include ethanol, ethanol, n-butanol, n- pentanol, n-propanol, 2-propanol, 2-butanol, tert-butanol, ethylene glycol; acetonitrile, propionitrile; tetrahydrofuran, diethyl ether, tert-butyl methyl ether, dimethoxyethane, 1,4- dioxane; dimethyl formamide, acetone, benzene, toluene, chloroform, and methylene chloride.
  • the aqueous/organic solvent system may be either a homogenous or heterogeneous mixture.
  • the aqueous component is water wherein the aqueous component of the solvent has a range between 10% and 90% on a volume basis.
  • the aqueous and organic components of the solvent are each approximately 50% on a volume basis.
  • Exemplary olefins include cis stilbene, trans stilbene, ethyl acrylate, styrene and C x -C 6 (alkyl) -cinnamate ester.
  • a preferred reaction temperature is within a range between -5.0 and 5.0 °C.
  • Figure 1 illustrates preffered cinchona alkaloid ligand derivatives.
  • Figure 2 shows a generic scheme indicating that a variety of olefins, as defined below, can be reacted smoothly with 1.1 equivalents of the oxidant/nitrogen donor to give the vicinal aminoalcohols in good yield and with high enantiomeric excess.
  • Figure 3 illustrates Table 1: Acetamide based asymmetric aminohydroxylation of various olefins wherein the indicated notations are defined as follows [a] Conditions: see experimental procedure, [b] From reaction catalyzed by (DHQ) 2 - PHAL. [c] Determined by ⁇ -NMR. [d] Determined by chiral HPLC (entry 1-4) or GC (entry 5) . [e] Negative values indicate the formation of the opposite enantiomer (product from reaction catalyzed by (DHQD) 2 -PHAL) . [f] Isolated yields of the pure products 1-5 after chromatography on silica gel. [g] tButanol/water 1:1 was employed, [h] KOH as base and 1-
  • Figure 4 illustrates a large scale synthesis based on acetamide as the oxidant for the amidohydroxylation.
  • Figure 5 illustrates regioselectivity preferences using AQN ligands and N-bromobenzamide.
  • Figure 6 illustrates the reversal of the regioselectivity with styrene derivatives wherein the indicated notations are defined as follows: [a] Conditions: see experimental procedure, [b] The DHQD-derivative was used, [c] Determined by ⁇ -NMR. [d] Determined by chiral HPLC. [e] Yields refer to the mixtures of isomers after chromatography on silica gel. [f] Not determined.
  • Figure 7 illustrates the effects on regio and stereochemistry using acetamide base amidohydroxylation using (DHQD) 2 PHAL (entries 1-3) or the (DHQD) 2 AQN (entries 4-6) ligands on the respective olefins (substrate olefins not shown) .
  • Figure 8 illustrates heterogenous conditions with a phase transfer catalyst wherein the stereochemistry is reversed using the indicated AQN ligand.
  • the ⁇ -aminoalcohol moiety is a widespread structural motif in natural products and synthetic drugs. Its generation in an enantioselective manner via metal catalysis represents a major challenge for synthetic organic chemists.
  • the catalytic asymmetric aminohydroxylation (AA) represents an even more elegant approach. Alkenes are therein converted into protected ⁇ -amino alcohols in a single step via a syn-cycloaddition catalyzed by osmium salts and chiral quinuclidine-type ligands derived from cinchona alkaloids.
  • Three major aspects are to be addressed in this reaction: namely, chemo-, regio-, and enantioselection.
  • the invention is therefore directed to a novel method for the regio-selective and enantio-selective conversion of olefins to ⁇ -hydroxyamides using an N-halo carboxamide as the oxidizing agent in the presence of an osmium catalyst and a chiral ligand.
  • a major advantage of this system is that only a stoichiometric amount of oxidant is needed, rather than an excess of oxidant, which greatly simplifies isolation and purification of the product. In fact, use of excess of oxidant does not improve the reaction in any way.
  • cinnamates are among the best substrates (Table 3, entries 1-3; the use of isopropyl cinnamates instead of the methyl esters is preferable in terms of greater stability towards hydrolysis and enhanced regioselectivity under the reaction conditions.
  • compounds 1 and 2 which are quite soluble in the reaction medium, the use of more than 50 % (v/v) water may result in slightly increased regioselectivities) .
  • the benzylic amides were formed with higher asymmetric induction (8, 85-96 % ee) than the benzylic alcohols (7, 62-94 % ee) , but poor regioselectivity was observed when phthalazine ligands were used.
  • our recently introduced anthraquinone (AQN) ligands Becker et al . Angew. Chem.
  • the phenyl glycinols (8) arise using the carbamate AA/phthalazine ligand combination and the adrenaline-type regioisomers (7) are preferentially derived using the acetamide AA/anthraquinone ligand combination.
  • Experiments with other substrates indicate that a reversal of regiochemistry occurs when anthraquinone derived ligands instead of phthalazines are used.
  • DHQ class dihydroquinine derived ligands
  • DHQD diastereomeric dihydroquinidine
  • the AA product was isolated by crystallization of the crude reaction mixture from ethyl acetate/hexane, and a second crop from diethyl ether. Subsequent hydrolysis furnished the enantiomerically pure aminoalcohol as the hydrochloride salt (9) in 68 % yield over two steps ( Figure 4) .
  • amidohydroxylation employing the use of N- bromoacetamide as the nitrogen source with styrenes as the olefin shows that the regiochemistry of aminoalcohol formation is reversed from that delivered by the carbamate version of the AA.
  • An efficient large scale synthesis of enantiomerically pure 3-phenylisoserine highlights the prodical potential of this latest advance in the osmium-catalyzed asymmetric aminohydroxylation process.
  • alkali metal salts of N-chloro carboxamides are unstable and readily undergo Hofmann rearrangement.
  • the N- bromo derivatives are preferred oxidants for amidohydroxylation reactions run at 4 °C.
  • the standard substrates are smoothly converted into protected amidoalcohols with N-bromo alkali (K + or Li + ) salts of acetamide.
  • K + or Li + N-bromo alkali
  • AQN ligands an anthraquinone spacer
  • the regiochemistry is reversed compared to the carbamate procedure with phthalazine (PHAL) ligands, see Figure 7.
  • PHAL phthalazine
  • anthraquinone-type (AQN) ligands such as (DHQ) 2 AQN or (DHQD) 2 AQN and acetamide
  • the major product is formed in high ee bearing the nitrogen substituent in the terminal position (adrenaline type products) .
  • the carbamate recipe gives similar regioselectivities in those cases but the ee's are low.
  • electron poor cinnamates e.g. ethyl 3-nitrocinnamate
  • the carbamate recipe gives low regioselectivities (typically 1:1) in those cases.
  • the amide-based nitrogen oxidant source is generally used in near stoichiometric amounts (eg. 0.90 - 1.2 equivalents; defined herein as near stoichiometric amounts) but can operate efficiently in the range of 0.50 equivalents (less for difficult purification conditions and inexpensive olefins) to 10 equivalents (for less reactive olefins) wherein the N-halo carboxamide can be commercially purchased or synthesized according to standard procedures well known in the art as disclosed vida supra.
  • the addition of an alkali metal in situ forms the alkali metal salt of the N-halo carboxamide.
  • N-halo carboxamide in a basic solution containing the alkali metal (eg. LiOH, NaOH, etc.).
  • alkali metal eg. LiOH, NaOH, etc.
  • the genus of amide-based nitrogen sources which are preferred with the invention include the following N-halo carboxyamides : N-fluoro- (C ⁇ C ⁇ (alkyl) ) -amide, N-chloro- (C t - C 15 (alkyl) ) -amide, N-bromo- (C !
  • aryl is defined as any substituted or unsubstituted aromatic containing amides and alkyl is defined as any C ⁇ C ⁇ aliphatic containing amides.
  • N-halo carboxyamides work optimally well with the procedure: N- bromoacetamide, N-chloroacetamide, N-bromobenzamide, N- chlorobenzamide, N-fluoro-2-chloro-acetamide, N-fluoro-2-bromo- acetamide, N-fluoro-2-iodo-acetamide, N-bromo-2-chloro- acetamide, N-bromo-2-bromo-acetamide, N-bromo-2-iodo-acetamide, N-iodo-2-chloro-acetamide, N-iodo-2-bromo-acetamide, N-iodo-2- iodo-acetamide, N-chloro-p-methoxy benzamide, N-chloro-2-methoxy acetamide, N-bromo-p-methoxy acetamide, N-bromo-p-methoxy benzamide,
  • AA asymmetric amidohydroxylation
  • three olefin classes 1) monosubstituted; 2) cis-disubstituted, and 3) trans-disubstituted olefins.
  • the 1,1 disubstituted and trisubstituted types of olefins give only racemic or low ee's while the tetrasusbstituted class, does not provide any signs of turnover; / ⁇ unsaturated esters, / ⁇ unsaturated amides, aromatic olefins and heteroaromatic olefins work particularly well with the invention.
  • High regioselectivity is one of the more useful features of the amidohydroxylation.
  • the chemistry exhibits a strong preference for nitrogen attachment to the olefinic carbon bearing an aromatic substituent or, in the case of olefins conjugated with a strong electron withdrawing group (EWG) , the nitrogen is strongly directed to the olefinic carbon distal to the EWG.
  • EWG electron withdrawing group
  • the alkaloid ligand is responsible for high regioselectivity. When the ligand is omitted, there is little preference for either regioisomer. Beyond probable contributions from "binding pocket" effects, the strong regioselection phenomenon requires the operation of powerful electronic determinants.
  • Preferred solvents include acetonitrile, n-propanol, tert- butanol and suitable solvents include methanol, ethanol, n- butanol, n-pentanol, n-propanol, 2-propanol, 2-butanol, tert- butanol, ethylene glycol; nitriles: acetonitrile, propionitrile; ethers: tetrahydrofurane, diethyl ether, tert. butyl methyl ether, dimethoxyethane, 1,4-dioxane; miscellaneous: dimethyl formamide, acetone, benzene, toluene, chloroform, methylene chloride.
  • Preferred ligands are shown in Figure 1 and are commercially available or synthesized by procedures well known in the art. Additional preferred ligands, which can be equally used with the invention with the specified concentrations as described herein, are as follows: p-phenylbenzoyl dihydroquinidine; acetyl dihydroquinine; dimethylcarbamoyl dihydroquinine; benzoyl dihydroquinine; 4-methoxybenzoyl dihydroquinine; 4- chlorobenzoyl dihydroquinine; 2-chlorobenzoyl dihydroquinine; 4- nitrobenzoyl dihydroquinine; 3-chlorobenzoyl dihydroquinine; 2- methoxybenzoyl dihydroquinine; 3-methoxybenzoyl dihydroquinine; 2-naphthoyl dihydroquinine; cyclohexanoyl dihydraquinine; p- phenyl
  • the ligand can range from ca. 0.5 to 10 mol % (less is appropriate for lower temperatures; eg. 0.5 % might be enough at 0 °C and 10 % would probably be needed to keep the % ee at reasonable levels if the temperature reaches 35 or 40 °C.
  • the osmium containing catalyst can be selected from any one of the various commercially available osmium sources including, but not restricted to potassium osmate dihydrate, osmium tetroxide, osmium (IV) oxide, osmium (IV) oxide dihydrate, osmium (III) chloride, and osmium hexachlorooxmate (IV) .
  • the amount of Os catalyst can range from 0.5% (probably even less in the very best cases, and in any case the number will drop as the process if further improved) to 10 or even 20%.
  • the general procedure conditions uses 4% to have fast reaction times, but 2% is good for most cases.
  • the high loadings of 20%, for example, is needed to achieve reasonable rates with very poor substrates (this conclusion follows from the extensive experience by us and others with the AD, where in desparate situations 20 or more % Os catalyst is needed.
  • the following table contains data on the amount of osmium and ligand one can use for the isopropyl cinnamate AA with N-bromo acetamide.
  • Tem era ure Vari ations For most cases, the hydroxyamide AA process is run between -5.0 and +5.0 degrees Celcius. There may be cases where up to 35 to 40 degrees may be advantageous depending on substrate.
  • Heterogeneous Condition Variation For most cases, the hydroxyamide AA process is run in homogeneous conditions, however, applying heterogeneous phase transfer conditions as illustrated in Figure 8, enhanced chemoselectivity was found for some olefins (see synthesis for: methyl (2S, 3R) -2- (benza ido) -3-hydroxy-3- (4-fluoro-3- nitrophenyl) propanoate 16, vida infra).
  • the AQN ligands furnished a complete reversal of the regioselectivity with cinnamates as olefins.
  • Phase Transfer Catalysts For heterogeneous conditions, a commercially available phase transfer catalyst such as tetra-n-butylammonium hydroxide is preferred, however other standard phase transfer catalysts (eg. tetra-alkyl ammonium or phosphonium salts) work well equally with the invention when heterogeneous conditions are required.
  • phase transfer catalyst such as tetra-n-butylammonium hydroxide
  • other standard phase transfer catalysts eg. tetra-alkyl ammonium or phosphonium salts
  • the hydroxyamide AA process is run in LiOH or KOH, however other alkali earth bases such as NaOH and CsOH are acceptable using the conditions and concentrations as indicated vida infra.
  • Preferred bases are LiOH, NaOH, KOH, NH 4 OH, alkyl or arylam onium hydroxides, and alkali or earth alkali salts of carbonates and bicarbonates (eg. Na 2 C0 3 , K 2 C0 3 , CaC0 3 , BaC0 3 et.)
  • NMR spectra were recorded on Bruker AMX-500, AM-300, or AM- 250 instruments. The following abbreviations were used to explain the multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; apt, apparent; b, broad; obs, obscured.
  • IR spectra were recorded on Nicolet 205, Perkin Elmer 1600 or Galaxy 2020 series FT-IR spectrophotometers . Optical rotations were recorded using a Perkin Elmer 241 polarimeter. High-resolution mass spectra (HRMS) were recorded on a VG ZAB- ZSE mass spectrometer under Fast Atom Bombardment (FAB) conditions, at the Scripps Research Institute.
  • the combined crystalline, white solid, 260 g is of 99 %ee as determined by HPLC on Chiralcel OD-H, Daicel, i-PrOH/hexane 40:60 v/v, 0.5 mL/min, 254 . nm; retention times: 8.2 min (2S, 3R) , 12.7 min ( 2R, 3S) .
  • the crude product was taken up in 500 mL ethyl acetate and passed through a 4.5-inch sintered glass funnel covered with a one inch layer of silica gel.
  • Product purification was accomplished by recrystallization from ethyl acetate/hexane 1:2 (4 mL/g) .
  • a second crop of material was obtained by trituration of the previously evaporated mother liquor with 100 mL Et 2 0 and subsequent filtration. Yield 119.5 g (71 % yield, 99 % ee) .

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Abstract

L'invention concerne des β-hydroxyamides synthétisés à partir de substrats d'oléfine au moyen d'une réaction d'addition asymétrique catalytique. Des N-halo carboxamides sont employés en tant que source d'azote oxydante pour la production de β-hydroxysulfonamides. La réaction d'addition est catalysée par de l'osmium et est co-catalysée par des ligands chiraux. Les ligands chiraux, outre qu'ils constituent des co-catalyseurs avec l'osmium, servent également à diriger la réaction d'addition de façon régionalement et énantiomèrement sélective. Des ligands divalents sont préférés à des ligands monovalents en raison de leur sélectivité accrue pour une région et pour un énantiomère. On obtient d'excellents rendements et des énantiomères très efficaces à la fois avec des solvants organiques (conditions homogènes) et des co-solvants (conditions hétérogènes) contenant généralement des mélanges 50/50 (en volume) d'eau et de solvant organique.
PCT/US1997/023511 1996-12-18 1997-12-18 Amidohydroxylation asymetrique catalytique d'olefines au moyen de n-halo carboxamides Ceased WO1998027051A2 (fr)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064625A1 (fr) * 2000-03-02 2001-09-07 Pharmacia & Upjohn Company Aminohydroxylation d'olefines en presente d'acetamide
FR2810666A1 (fr) * 2000-06-22 2001-12-28 Rhodia Chimie Sa Ligands chiraux de type (beta-aminoalkyl)-phosphine, -phosphite, -phosphonite et -phosphinite, complexes metalliques correspondants et leur utilisation dans la catalyse asymetrique
US8987504B2 (en) 2010-06-18 2015-03-24 Victoria Link Limited Aminohydroxylation of alkenes

Family Cites Families (1)

* Cited by examiner, † Cited by third party
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DE68924418T2 (de) * 1988-01-11 1996-03-28 Massachusetts Inst Technology Durch komplexmittel beschleunigte katalytische asymmetrische dihydroxylierung.

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001064625A1 (fr) * 2000-03-02 2001-09-07 Pharmacia & Upjohn Company Aminohydroxylation d'olefines en presente d'acetamide
US6509491B2 (en) 2000-03-02 2003-01-21 Pharmacia & Upjohn Company Aminohydroxylation of olefins in the presence of acetamide
FR2810666A1 (fr) * 2000-06-22 2001-12-28 Rhodia Chimie Sa Ligands chiraux de type (beta-aminoalkyl)-phosphine, -phosphite, -phosphonite et -phosphinite, complexes metalliques correspondants et leur utilisation dans la catalyse asymetrique
US8987504B2 (en) 2010-06-18 2015-03-24 Victoria Link Limited Aminohydroxylation of alkenes

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