Stereoselectivity of 6-Exo Cyclization of α-Carbamoyl Radicals

Article abstract of DOI:10.1021/acs.joc.6b00008

The stereoselectivity in the 6-exo cyclization of α-carbamoyl radicals was investigated experimentally and theoretically. The BEt₃/O₂-initiated iodine-atom-transfer radical cyclization reactions of substituted N-(but-3-en-1-yl)-N-(tert-butyl)-2-iodoalkanamides were carried out, which led to the predominant formations of 3,4-cis, 4,5-trans, or 4,6-trans substituted δ-lactams. Density functional calculations at the B3LYP/6-31G? level revealed that the 6-exo radical cyclization proceeds via boat-conformational transition states. Furthermore, a mechanistic insight into the stereoselectivity was provided and the calculation results were in excellent agreement with the experimental observations.