Trisoxazoline/Cu(II)-promoted Kinugasa reaction.: Enantioselective synthesis of β-lactams

The reactions of nitrones with terminal alkynes, catalyzed by chiral Pr-i-trisoxazoline 2a/CU(ClO4)(2)center dot 6H(2)O under air atmosphere, afforded beta-lactams in moderate to good yields with up to 85% ee. The diastereoselectivity depends on the alkyne. Propiolate gives the trans-isomer as a major product, while the other alkynes afford cis-disubstituted lactams predominantly. Copper(II) salt proved to be an efficient catalyst precursor for the first time in the Kinugasa reaction, and this allowed the reaction to be performed under a practical and convenient condition. An appropriate base used in this reaction was essential to control both diastereoselectivity and enantio selectivity. Compared with primary and tertiary amines, secondary amines gave higher enantioselectivities. The reaction scope and limitation as well as the mechanism were also studied.