Asymmetric Conjugate Addition of Unmodified Cyclic Ketones to Nitroolefins Using Aminophosphonate as the Organocatalyst

Abstract

α-Aminophosphonates are an important class of compounds with diverse and useful biological activities. Despite that their structues are similar to that of proline, however, chiral cyclic α-aminophosphonates have found little applications in catalytic asymmetric synthesis. In this paper, an enantiopure α-aminophosphonate has been synthesized and was found to be effective as a chiral organocatalyst for the asymmetric conjugate addition of cycloketones to β-nitrostyrenes. With a catalyst loading of 20 mol% and in the presence of 10 mol% of CF 3 COOH as a cocatalyst, the Michael adducts could be obtained with varying degrees of diastereo-and enantioselectivities (up to 97∶3 and 90% ee respectively) under solvent-free conditions.

Synthetic methods of cyclic α-aminophosphonic acids and their esters

“…[58][59][60][61][62] Hydrogenolysis of 82, followed by acidic hydrolysis of the phosphonate moiety with 6 M HCl and subsequent treatment with propylene oxide led to (S)-phosphopyrrolidine 25 (Scheme 30). …”