Highly Enantioselective Conjugate Additions of Phosphites to alpha,beta-Unsaturated N-Acylpyrroles and Imines: A Practical Approach to Enantiomerically Enriched Amino Phosphonates

The first highly enantioselective phosphonylation of alpha,beta-unsaturated N-acylpyrroles has been developed. Excellent yields (91-99%) and enantioselectivities (up to >99% enantiomeric excess (ee)) were observed for a broad spectrum of both phosphites and N-acylpyrroles under mild conditions. In particular, when diethyl phosphite was employed to test the scope of the N-acylpyrroles, almost optically pure products (98 to > 99 % ee) were obtained for 20 examples of N-acylpyrroles. Moreover, optically pure alpha-substituted beta- or gamma-amino phosphonates can be obtained by several simple transformations of the pyrrolyl phosphonates. The versatility of the N-acylpyrrole moiety makes the phosphorus adducts powerful chiral building blocks that enable the synthesis of various phosphonate-containing compounds. Finally, the present strategy can also be applied to the asymmetric hydrophosphonylation of N-acylimines with high enantioselectivities (93 to > 99 % ee).