Cobalt-Catalyzed Stereoselective Synthesis of 2,5-trans-THF Nitrile Derivatives as a Platform for Diversification: Development and Mechanistic Studies

A straightforward protocol integrating a sustainable approach for the synthesis of new 2,S-trans-THF nitrile derivatives enabling an easy diversification of its side chain scaffolds is described. The reaction tolerated different aromatic and alkyl substituents, affording the corresponding 2,5-trans-THFs in high diastereoselectivity. A detailed mechanistic study using DFT calculation reveals details of the ligand-exchange step, suggesting an inner-sphere syn attack to form the 2,5-trans stereochemistry as the most likely pathway, excluding the previous cation radical intermediate. The formation of a Co-C intermediate is suggested on the basis of the homolytic cleavage to give the previously proposed free carbon radical intermediate.