Stereoselective Synthesis of -Fluoro Carboxylic Acids by Ireland-Claisen Rearrangement

Stereoselective synthesis of & alpha;-fluoro carboxylicacids bythe Ireland-Claisen rearrangement can provide a straightforwardapproach to this class of compounds. We report a systematic investigationof base-dependent stereocontrol in the Ireland-Claisen rearrangementof & alpha;-fluoro esters. For substrates with various substitutionpatterns, the use of KN(SiMe3)(2) in toluene affordedrearrangement products corresponding to the (Z)-enolateintermediate with a practically useful diastereoselectivity and yield.In contrast, lower yields and diastereoselectivity were consistentlyobserved with the use of lithium diisopropylamide (LDA) in tetrahydrofuran(THF).