Catalytic asymmetric addition of β-keto phosphonates to an activated imine—formation of optically active functionalized phosphonate α-amino acid derivatives

Abstract

The direct stereoselective addition of an activated imine to β-keto phosphonates in the presence of chiral Lewis acid complexes is developed. The evaluation of different activated imines shows that an N-tosyl-α-imino ester adds in a diastereo- and enantioselective fashion to β-keto phosphonates activated by especially chiral copper(II)-bisoxazoline complexes. An evaluation of Lewis acids, chiral ligands and reaction conditions, such as solvent, bases and other additives, shows that high yields, moderate diastereoselectivity and good enantioselectivity are obtained. The scope of the reaction is demonstrated for the reaction of β-keto phosphonates and finally, the mechanism for the catalytic stereoselective step is presented.