Enantioselective synthesis of α,α-difluoro-ß-lactams using amino alcohol ligands.

A practical and highly enantioselective Reformatsky reaction of ethyl bromodifluoroacetate with imines using a cheap and commercially available amino alcohol ligand is described. A variety of α,α-difluoro-ß-lactams were obtained in up to 74% yield with high enantioselectivity in excess of 99% ee. The use of ethyl bromodifluoroacetate provides for ease of operation because of the inherent chemical stability of this reagent.

Ligand-promoted asymmetric imino-Reformatsky reaction of ethyl dibromofluoroacetate.

An enantioselective Reformatsky reaction has been developed for the reaction of ethyl dibromofluoroacetate (1) with an imine. This method represents the first ligand-promoted imino-Reformatsky approach to use a halofluoroacetate. The use of an amino alcohol ligand allowed for the preparation of enantioenriched α-bromo-α-fluoro-ß-lactams in good yields with enantioselectivities up to 96% ee. This process also provided access to ß-lactam rings bearing two stereogenic centers.