Nucleophilic substitution on α-mesyloxy-O-alkyloximes - I. Enantiospecific synthesis of 2-(imidazol-1-yl) -1,3-diphenylpropan-1-one o-alkyloximes

Article abstract of DOI:10.1016/S0957-4166(96)00505-8

An enantiospecific synthesis of (S)- and (R)-(E)-5-[1,3-diphenyl-2-(imidazol-1-yl)propylidene] aminooxypentanoic acids 1 using homochiral phenylalanines as starting material is described. Chiral α-hydroxyketones 9 were obtained from α-hydroxyacids 7 by Weinreb's ketone synthesis. 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 displayed by compound 3 compromised its use in an enantiospecific synthesis. Homochiral compounds 1 were then obtained by a nucleophilic substitution on α-mesyloxy-O-alkyloxymes 14 which were in turn obtained from 9. This nucleophilic substitution on α-mesyloxy-O-alkyloxymes was not previously reported either on homochiral compounds or on racemic derivatives.