ASYMMETRIC HALOLACTONIZATION REACTION .1. ASYMMETRIC SYNTHESIS OF OPTICALLY-ACTIVE ALPHA,ALPHA-DISUBSTITUTED-ALPHA-HYDROXY ACIDS FROM ALPHA,BETA-UNSATURATED ACIDS BY THE NOVEL USE OF HALOLACTONIZATION REACTION

Considering the usefulness of optically active α,α-disubstituted -α -hydroxy acids (1) andα,α- disubstituted-α-hydroxy ketones (2) readily accessible from 1 exploitation of a new asymmetric synthesis of 1 from α,β-unsaturated acids (3) which utilised halolactonisation reaction as its key step, was studied. The asymmetric bromolactonisation of (S) N-(α, β-unsaturated)acylproline((S) 5) derivable from 3 such as tiglic acid (3a) and trans-α methylcinnamic acid (3b), with N-bromosuccinimide in N,N dimethylformamide was found to proceed in a highly stereoselective and regiospecific manner giving a mixture of the two diastereomeric bromolactones (8) in which one diastereomer (8A) was highly predominant. Debromination of 8 followed by acidic hydrolysis readily afforded (R)-1 being 89-98% optically pure. © 1979.