First highly diastereoselective synthesis of syn alpha-methyl beta-fluoroalkyl beta-amino esters

[GRAPHICS] A new two-step approach for the diastereoselective synthesis of the syn alp ha-methyl beta-fluoroalkyl beta-amino esters 4 has been developed. This app roach is based on the chemical reduction of the fluorinated beta-enamino es ters 3, which have been previously obtained from imidoyl chlorides 1 and li thium ester enolates, with Znl(2)/NaBH4 as the reducing agent. The process takes place with high syn diastereoselectivity and good to excellent yields . A metal-chelated six-membered model has been suggested to explain the ste reochemical outcome of the reduction reaction.