Theoretical Elucidation of Kinetic and Thermodynamic Control of Radical Addition Regioselectivity

The cyclizations of two structurally similar 2-oxo-5-hexenyl-type radicals have been investigated
by ab initio and density functional (UB3LYP/6-31+G**//UHF/6-31G* and UB3LYP/6-31G*//UB3LYP/6-31G*)
calculations. The origin of apparently contradictory reports of 6-endo and 5-exo cyclizations is determined.
Kinetic control favors 6-endo cyclization, while thermodynamic control gives 5-exo cyclization, and the
observation of different products from different research groups arises from the difference in experimental
conditions used by the two groups. The outcome of a new cyclization reaction was predicted by using
these theoretical techniques. Kinetic control is predicted to yield exclusively the products of 6-endo
cyclization, while thermodynamic control would lead to an approximately equal mixture of one 6-endo and
one 5-exo cyclized product. Experimental studies revealed that the reaction yields only the products of
6-endo cyclization through kinetic control.