Direct and Stereoselective Synthesis of Diversely Substituted 2,4-trans-(NH)-Pyrrolidines by Copper(I)-Catalyzed Radical Cyclization at Low Temperature

Article abstract of DOI:10.1002/adsc.201600844

This work describes a successful copper(I)-catalyzed radical cyclization of β-haloethylallylamines bearing an unprotected NH-group while retaining catalyst-redox activity. The cyclization occurs regio- and diastereoselectively at 0 °C and furnishes diversely substituted 1,3-trans-(NH)-pyrrolidines directly in high isolated yields. An involvement of the bulky copper complex in the cyclization step as the possible reason for the diastereoselectivity was proposed. Synthetic applications of the products in the preparation of useful 4-chloro-NH-pyrrole in a single step, has also been demonstrated. A quick, mild and general method involving simple addition of trichloroacetic acid/dimethyl sulfoxide (CCl₃CO₂H-DMSO) solution to readily accessible N-allylaldimines and ketimines tolerating acid-sensitive and highly deactivating substituents was developed to access the amine precursors. (Figure presented.).