Copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of 1,3-enynes and azomethine ylides

Abstract

Herein, we report a copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and 1,3-enynes, which provides a series of chiral poly-substituted pyrrolidines in high regio-, diastereo-, and enantioselectivities. Both 4-aryl-1,3-enynes and 4-silyl-1,3-enynes serve as suitable dipolarophiles while 4-alkyl-1,3-enynes are inert. Moreover, the method is successfully applied in the construction of both tetrasubstituted stereogenic carbon centers and chiral spiro pyrrolidines. The DFT calculations are also conducted, which imply a concerted mechanism rather than a stepwise mechanism. Finally, various transformations started from the pyrrolidine bearing a triethylsilylethynyl group and centered on the alkyne group are achieved, which compensates for the inertness of 4-alkyl-1,3-enynes in the present reaction.

One of the most efficient method to access chiral poly-substituted pyrrolidines is the catalytic asymmetric 1,3-dipolar cycloaddition, but using this reaction with weakly activated alkenes remains elusive. Here, the authors disclose a copper(I)-catalyzed asymmetric 1,3-dipolar cycloaddition of azomethine ylides and 1,3-enynes.