Stereoselection at the steady state. Group selective radical cyclizations of substrates containing two radical precursors and one radical acceptor

The kinetic model for compound stereoselection presented in previous paper is verified experimentally by conducting a series of radical cyclizations of 1-(3-halo-2-(halomethyl)propyl)cycloalk-2-enecarboxylates with tributyltin hydride and measuring the ratios of products. Cyclization rate constants are abstracted from the data by an analysis that minimizes total error, and these rate constants compare favorably with rate constants that we measured directly on the corresponding monohalides. Transition state modeling was used to interpret the initial round of results and to design two new systems, one of which was predicted to cyclize with higher selectivity than the parent and the other of which was predicted to cyclize with reverse selectivity. These substrates bearing 4-tert-butyl groups were synthesized, and the experimental results verified the computational predictions.