KINETIC AND MECHANISTIC STUDIES OF THE TANDEM ENEDIYNE-RADICAL CYCLIZATION

Enediynes 11 possessing a tethered olefin radical acceptor can participate in a tandem enediyne-radical cyclization to yield dihydrobenzindene derivatives 16. In the present study, the mechanism of this reaction was investigated utilizing kinetic studies to determine whether the mechanism was a radical chain, stepwise, or concerted process. Substrate concentration, 1,4-cyclohexadiene concentration, olefin geometry, and olefin electronics were varied. These experiments demonstrate that the reaction occurs under first-order kinetics over a wide variation in either substrate or 1,4-CHD concentration. The reaction rate is also independent of olefin geometry and olefin electronics. The rate constants for the reactions were similar and ranged from 3.0 X 10(4) s-1 to 6.0 X 10(-4) s-1. The data suggests that the tandem enediyne-radical cyclization proceeds through a distinct 1,4-diyl reactive intermediate such as 5 formed in the rate-determining enediyne cyclization step, followed by a radical cyclization to give 16. The tandem enediyne-radical cyclization mechanism is supported by trapping the intermediate biradical 18 in a tandem enediyne-6-exo-radical cyclization of 17 to give products 19a,b.