NUCLEOPHILIC-SUBSTITUTION ON ALPHA-MESYLOXY-O-ALKYLOXIMES .1. ENANTIOSPECIFIC SYNTHESIS OF 2-(IMIDAZOL-1-YL)-1,3-DIPHENYLPROPAN-1-ONE O-ALKYLOXIMES

An enantiospecific synthesis of (S)- and -(E)-5-[1,3-diphenyl-2-(imida zol-l-yl)propylidene] aminooxypentanoic acids 1 using homochiral pheny lalanines as starting material is described. Chiral alpha-hydroxyketon es 9 were obtained from alpha-hydroxyacids 7 by Weinreb's ketone synth esis. Imidazole introduction by nucleophilic substitution on mesylate 10 led to 2-(imidazol-1-yl)propan-1-one derivative 3, key intermediate in the synthesis of 1. However, the low configurational stability dis played by compound 3 compromised its use in an enantiospecific synthes is. Homochiral compounds 1 were then obtained by a nucleophilic substi tution on alpha-mesyloxy-O-alkyloxymes 14 which were in turn obtained from 9. This nucleophilic substitution on alpha-mesyloxy-O-alkyloxymes was not previously reported either on homochiral compounds or on race mic derivatives. (C) 1997 Elsevier Science Ltd.