The present invention relates to a process for the synthesis of chiral enantiomerically pure .beta.-amino alcohols which are extraordinarily important as therapeutic agents for the treatment of a variety of human disorders and as chiral auxiliaries in organic synthesis. The hydroboration of enamines is a versatile and convenient method for the synthesis of both racemic and enantiomerically pure .beta.-amino alcohols in high yields. This methodology enables the synthesis of virtually any .beta.-amino alcohol. Hydroboration of these enamines with chiral organic borohydrides, e.g. either mono- or diisopinocampheylborane, followed by oxidation with aqueous or solid NaOH/30% H.sub.2 O.sub.2 or Me.sub.3 NO, gives the corresponding chiral .beta.-amino alcohol. Enantiomeric excesses ranged from 60% for reactions run at 25.degree. C. to greater than 99% for reactions run at -25.degree. C.
This is a continuation of copending application of Ser. No. 07/847,171 filed on Mar. 6, 1992, now abandoned, which is a continuation-in-part of the application Ser. No. 07/848,427 filed on Mar. 6, 1992, now abandoned.
A process is provided for preparing chirally pure S-enantiomers of .alpha.-amino acids comprising the steps of: a) preparing an organometallic reagent from an alkyl halide of the formula (R).sub.2 CH(CH.sub.2).sub.n CH.sub.2 X; b) adding the organometallic reagent to carbon dioxide to afford a carboxylic acid; c) activating the carboxylic acid with an acid chloride, phosphorus trichloride, acid anhydride, or thionyl chloride in the presence of a tertiary amine base; d) reacting the product of step c) with an alkali metal salt of S-4-benzyl-2-oxazolidinone; e) treating the product of step d) with a strong non-nucleophilic base to form an enolate anion; f) trapping the enolate anion with 2,4,6-triisopropylbenzenesulfonyl azide to afford an oxazolidinone azide; g) hydrolyzing the oxazolidinone azide with an aqueous base to afford an .alpha.-azido acid; h) reducing the .alpha.-azido acid to the .alpha.-amino acid; and i) recrystallizing the .alpha.-amino acid to the chirally pure .alpha.-amino acid. A process is also provided for preparing chirally pure S-enantiomers of .beta.-amino alcohols further comprising the steps of reducing the crude .alpha.-amino acid to the .beta.-amino alcohol and recrystallizing the .beta.-amino alcohol to the chirally pure .beta.-amino alcohol. A process is further provided for preparing chirally pure S enantiomers of N-sulfonyl .beta.-amino alcohols further comprising the steps of sulfonylating the .beta.-amino alcohol with 5-chloro-thiophene-2-sulfonyl halide; and recrystallizing to afford the chirally pure N-sulfonyl .beta.-amino alcohols.
