Trisoxazoline/Cu(II)-Promoted Kinugasa Reaction. Enantioselective Synthesis of β-Lactams

Abstract
The reactions of nitrones with terminal alkynes, catalyzed by chiral iPr-trisoxazoline 2a/Cu(ClO4)2·6H2O under air atmosphere, afforded β-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 enantioselectivity. Compared with primary and tertiary amines, secondary amines gave higher enantioselectivities. The reaction scope and limitation as well as the mechanism were also studied.

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