Synthesis of Pyrrolidines by Cobalt-Catalyzed Intramolecular Cyclization

Significance

A synthesis of pyrrolidines by cobalt-catalyzed intramolecular cyclization of allyl 2-iodoethyl amines is reported. The reaction proceeds typically via radical generation by single-electron transfer from a cobalt complex, followed by cyclization, capture of the 3-pyrrolidinomethyl radical by the cobalt complex, and reductive elimination. Coupling with a trialkylsilylmethyl Grignard reagent led to a 3-(silylethyl)pyrrolidine derivative which was oxidized to the corresponding alcohol by the Tamao-Fleming procedure while reaction with 1-alkynyl Grignards gave propargylic pyrrolidines. Use of an NHC ligand was important for the success of the latter reaction, as conditions for TMEDA/Co-mediated alkynylation of alkyl halides are incompatible with alkyl-substituted alkynyl Grignards. The intramolecular cross-coupling reaction was also used to prepare tetrahydrofuran and cyclopentane derivatives. The scope of the reaction was insufficiently explored.