Copper-Catalyzed Diastereo- and Enantioselective Decarboxylative [3+2] Cyclization of Alkyne-Substituted Cyclic Carbamates with Azlactones: Access to γ-Butyrolactams Bearing Two Vicinal Tetrasubstituted Carbon Stereocenters

A copper-catalyzed diastereo-and enantioselective decar-boxylative [3 + 2] cyclization reaction of alkyne-substituted cyclic carbamates with azlactones has been established. A range of optically pure gamma-butyrolactams bearing two vicinal tetrasubstituted carbon stereo-centers were obtained in high yields with good to excellent stereo-selectivities (up to 99% yield, 99:1 dr, and 99% ee). This is the first example of asymmetric synthesis gamma-butyrolactams containing sterically congested vicinal tetrasubstituted stereocenters via a decarboxylative cyclization pathway.

Automated summary

A copper-catalyzed decar-boxylative [3 + 2] cyclization reaction between alkyne-substituted cyclic carbamates and azlactones has been developed, providing optically pure gamma-butyrolactams bearing two adjacent tetrasubstituted carbon stereocenters in high yields with excellent stereo-selectivities (up to 99% yield, 99:1 dr, and 99% ee). This represents the first successful asymmetric synthesis of gamma-butyrolactams containing sterically congested adjacent tetrasubstituted stereocenters via a decarboxylative cyclization pathway.