Stereoselective synthesis of certain trifluoromethyl-substituted alcohols

A process for stereoselective synthesis of a compound of Formula (X) or Formula (X′)

• wherein:
• R1 is an aryl, heteroaryl, or C5-C15 cycloalkyl group, each optionally substituted with one to three substituent groups,
• wherein each substituent group of R1 is independently C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C5 alkoxy, C2-C5 alkenyloxy, C2-C5 alkynyloxy, aryloxy, acyl, C1-C5 alkoxycarbonyl, C1-C5 alkanoyloxy, C1-C5 alkanoyl, aroyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C1-C5 alkylaminocarbonyloxy, C1-C5 dialkylaminocarbonyloxy, C3-C5 cycloalkylaminocarbonyloxy, C1-C5 alkanoylamino, C1-C5 alkoxycarbonylamino, C1-C5 alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, C1-C5 dialkylaminosulfonyl, halogen, hydroxy, carboxy, cyano, trifluoromethyl, trifluoromethoxy, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C1-C5 alkyl or aryl;
• or ureido wherein either nitrogen atom is optionally independently substituted with C1-C5 alkyl or C3-C5 cycloalkyl;
• or C1-C5 alkylthio,
• wherein each substituent group of R1 is optionally independently substituted with one to four substituent groups selected from aryl or heterocyclyl wherein the heterocycle is optionally independently substituted with hydroxyl, halogen, methyl, or dialkylamino;
• C1-C5 alkoxycarbonyl, methyl, methoxy, halogen, hydroxy, oxo, cyano, aminosulfonyl, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C1-C5 alkyl or C1-C3 dialkylamine or aryl;
• or ureido wherein either nitrogen atom is optionally independently substituted with C1-C5 alkyl;
• or oxime wherein the oxygen atom is optionally substituted by C1-C5 alkyl or benzyl;
• R2 and R3 are each independently hydrogen, C1-C5 alkyl, or C5-C15 arylalkyl group, or R2 and R3 together with the carbon atom they are commonly attached to form a C3-C8 spiro cycloalkyl ring, or
• R1 and R2 when taken together are a chromanyl or dihydrobenzofuranyl optionally substituted with C1-C5 alkyl, C2-C5 alkenyl, C2-C5 alkynyl, C3-C8 cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C5 alkoxy, C2-C5 alkenyloxy, C2-C5 alkynyloxy, aryloxy, acyl, C1-C5 alkoxycarbonyl, C1-C5 alkanoyloxy, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, aminocarbonyloxy, C1-C5 alkylaminocarbonyloxy, C1-C5 dialkylaminocarbonyloxy, C1-C5 alkanoylamino, C1-C5 alkoxycarbonylamino, C1-C5 alkylsulfonylamino, aminosulfonyl, C1-C5 alkylaminosulfonyl, C1-C5 dialkylaminosulfonyl, halogen, hydroxy, carboxy, oxo, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethylthio, nitro, or amino wherein the nitrogen atom is optionally independently mono- or di-substituted by C1-C5 alkyl;
• or ureido wherein either nitrogen atom is optionally independently substituted with C1-C5 alkyl;
• or C1-C5 alkylthio wherein the sulfur atom is optionally oxidized to a sulfoxide or sulfone,
• the process comprising:
• (a) reacting the starting material of formula A with a chiral sulfoxide anion source B or B′, where R is an alkyl or aryl group and M is a counter-cation, in a suitable solvent to prepare a compound of formula C or C′, respectively
• (b) reducing the sulfoxide of formula C or C′ in a suitable solvent to obtain the compound of formula D or D′, respectively
• (c) cyclizing the compound of formula D or D′ in a suitable solvent to form the epoxide compound of Formula (X) or Formula (X′), respectively