The Asymmetric Difluoro‐Reformatsky Reaction

The structural motif of α,α-difluoro-substituted carboxyl and carbonyl groups with hydroxy- or amino-substituents at the stereogenic carbon in β-position is found frequently drugs biologically active compounds. A straightforward method for obtaining those targets high enantiomeric purity given by asymmetric difluoro-Reformatsky imino-difluoro-Reformatsky reactions that lead to α,α-difluorinated β-hydroxy- β-amino-carboxylates β-lactams. Three concepts open a route this type compounds are discussed here. Firstly, chiral substrates able induce stereoselectivity formation newly created center. Secondly, covalently bound removable auxiliaries used syntheses and, thirdly, additives ligands metal direct addition zinc enolate, Reformatsky reagent, aldehydes imines an enantioselective manner. review closes short discussion more recently developed difluoro-aldol may be considered as alternatives procedure.