Radical cyclization reactions via radical translocations

Abstract

The radical reactions of vinyl epoxides and keto epoxides via radical translocation have been studied. The radical reactions of endocyclic vinyl epoxides afforded the cis-fused bicyclic compounds as a mixture of antisyn diastereomers through a sequential process of $Bu_3Sn$ radical addition, epoxide fragmentation to the alkoxy radical, 1,5-H atom transfer from carbon to oxygen, cyclization, and termination via ejection of $n-Bu_3Sn$ radical. The existence of a radical stabilizing group on the side chain improved the yield and the only detectable byproduct was an enone, which was resulted from β-cleavage of the tertiary alkoxy radical intermediate. The radical reaction of epoxy silyl enol ethers also gave the cis-fused bicyclic compounds and showed the excellent stereoselectivity in contrast to the reaction of vinyl epoxides. The phenylthio radical mediated cyclization prevented the formation of enone but the diastereoselectivity was relatively low. In all cases, the anti-isomer was major and the diastereoselectivity varied with the change of the radical mediator and the substituent on the substrate. Tributyltin radical addition to the endocyclic keto epoxides formed initially the O-stannyl ketyl radical and the epoxide ring opening reaction proceeded rapidly, yielding the tertiary alkoxy radical which underwent the 1,5-H atom transfer and cyclization. This sequential reaction afforded cis-fused bicylic keto alcohols as a diastereomic mixture along with starting enones and 1,3-diketones and the geometry of the major isomer was confirmed to be syn-. In the case of exocyclic ketoepoxides, β-carbonyl carbon-centered radicals were generated via 1,5-Sn group transfer from oxygen to oxygen and underwent cyclization to afford [6-5] and [6-6] bicyclic compounds in 3:1 ratios. When acyclic α, β-epoxy ketones were treated with tributyltin hydride, cyclic keto alcohols were obtained as a mixture of diastereomers along with direct reduction products, via $1,5-Bu_3Sn$ group ...