Synthesis of Pyrrolizidines and Indolizidines via Radical 1,5-Hydrogen Transfer

Significance

Reported here is a synthesis of 1-azabicyclic compounds via a thiophenol-mediated 1,5-hydrogen transfer-cyclization process of N-homopropargylic pyrrolidinones and piperidinones. This reaction sequence proceeds efficiently for 1,1- and 1,2-disubstituted N-homopropargylic amines which were prepared via addition of allenylzinc species to imines derived from γ- and δ-aminoesters. Two mechanistic proposals were given: a) 5-exo-trig cyclization of an α-aminyl radical generated by addition of a thiyl radical followed by 1,5-H atom transfer and b) 5-exo-dig cyclization of the α-aminyl radical resulting from direct H-atom abstraction by the thiyl radical. Deuterium-labeling experimental results support pathway a) rather than b).