SYNTHESIS AND DETERMINATION OF ENANTIOMERIC EXCESSES OF NON-RACEMIC TERT-THIOLS DERIVED FROM CHIRAL SECONDARY α-MERCAPTOCARBOXYLIC ACIDS.

Article abstract of DOI:10.1016/S0040-4020(01)87682-1

The optically active α-mercapto derivatives of propanoic, 3-phenylpropanoic, 2-phenylacetic, 3-methylbutanoic, 4-methylpentanoic, and (S)-3-methylpentanoic acids have been prepared.Condensation of these acids with pivalaldehyde gives 2-t-butyl-5-substituted-1,3-oxathiolanones (6); the cis geometric isomers are formed in excess and are obtained pure by crystallization.For the 5-benzyl derivative (6b) the cis arrangement for the major diastereomer was established by X-ray crystallography.These cis-disubstituted heterocycles (6), after deprotonation with lithium diisopropylamide (LDA) or lithium hexamethyldisilazide (LHMDS) and subsequent reaction with electrophiles such as alkyl halides, aldehydes, or ketones, furnish, after hydrolysis, in high enantiomeric excesses α-branched α-mercaptocarboxylic acids or esters (9).These result from an overall substitution of the proton in the α-position to the carbonyl group with retention of configuration and without racemization.This stereochemical course was established by a crystal structure determination of (2S)-8e obtained by benzylation of the enolate derived from cis-5-phenyl-1,3-oxathiolan-4-one (6c).The tert-α-mercaptocarboxylic acids are obtained optically active without employment of a chiral auxiliary.Their enantiomeric excesses were determined by esterification, conversion to diastereomeric phosphonodithionates on reaction with CH3POCl2, followed by integration of the well separated proton-decoupled (31)P NMR signals.This is apparently the first example of enantiomeric excess determinations of chiral tertiary thiols.