Kinetic and Mechanistic Studies of the Tandem Enediyne-Radical Cyclization

Article abstract of DOI:10.1021/jo00072a026

Enediynes 11 possesing 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 eithersubstrate 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 3.0E-4 s^-1 to 6.0E-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.