Palladium-Catalyzed Asymmetric [3+2] Cycloadditions towards Pyrrolidines

Significance

The palladium-catalyzed [3+2]-trimethylenemethane (TMM) cycloaddition, a 30-year-old reaction, has seen a recent resurgence due to the development of asymmetric variants. One such transformation is the use of aldimines towards the synthesis of chiral pyrrolidines (J. Am. Chem. Soc. 2007, 129, 12398). A much greater challenge is the use of more bulky, electron-rich ketimine substrates, which would provide pyrrolidines containing a tetrasubstituted center. The authors report that using a cyano TMM donor and phosphoramidite ligands, a broad range of N-tosyl imines undergo [3+2] cycloadditions with excellent enantio- and diastereoselectivity.