8-Endo versus 7-Exo Cyclization of α-Carbamoyl Radicals. A Combination of Experimental and Theoretical Studies

Atom transfer radical cyclization reactions of N-(4-pentenyl)iodoacetamides were investigated. The
reactions were efficiently promoted by BF3·OEt2. For N-alkenyl-substituted iodoamides, excellent
regioselectivity in favor of 8-endo cyclization was observed, while both 7-exo and 8-endo cyclization
products were formed with the 8-endo cyclization preferred in the cases of N-(2-allylphenyl)-substituted iodoamides. Density functional theory calculations at the B3LYP/6-31G* level revealed
that both the s-trans and the s-cis conformational transition structures were feasible for the 8-endo
cyclization of N-alkenyl-substituted α-carbamoyl radicals while 7-exo transition structures were
much less stable. For the cyclization of N-(2-allylphenyl)-substituted α-carbamoyl radicals, the
transition structures for 8-endo and 7-exo cyclizations were of comparable energy. These results
were in excellent agreement with the experimental observations.