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

An enantiospecific synthesis of (S)- and enyl-2(imidazol-1-yl)propylid ene]aminooxypentanoic acids 2 using homochiral phenylalanines as start ing material is described. Protected alpha-hydroxy-N,O-dimethylamides 4, obtained from alpha-hydroxyacids 3 were coupled with 1-cyclohexenyl lithium to afford alpha,beta-enones 5, which were in turn converted to alpha-hydroxyketones 6. Configurational liability of compound 11, pro mpted us to attempt imidazole introduction on the alpha-hydroxy-O-alky loxymes 12 which proved to be configurationally more stable. Thus nucl eophilic substitution on alpha-mesyloxy-O-alkyloxymes 14 led, after es ter removal, to homochiral compounds 2. The use of hydrogenolysis for 14b deblocking provided 2a with 97% ee. Considerations on the stereoch emical outcome of this hitherto undescribed nucleophilic substitution on alpha-mesyloxy-O-alkyloxymes are reported. (C) 1997 Elsevier Scienc e Ltd.