Multi-site programmable functionalization of alkenes via controllable alkene isomerization

Direct and selective functionalization of hydrocarbon chains is a fundamental problem in synthetic chemistry. Conventional functionalization of C=C double bonds and C(sp(3))-H bonds provides some solutions, but site diversity remains an issue. The merging of alkene isomerization with (oxidative) functionalization provides an ideal method for remote functionalization, which would provide more opportunities for site diversity. However, the reported functionalized sites are still limited and focus on a specific terminal position and internal site; new site-selective functionalization, including multi-functionalization, remains a largely unmet challenge. Here we describe a palladium-catalysed aerobic oxidative method for the multi-site programmable functionalization, involving the C=C double bond and multiple C(sp(3))-H bonds, of terminal olefins via a strategy that controls the reaction sequence between alkene isomerization and oxidative functionalization. Specifically, 1-acetoxylation (anti-Markovnikov), 2-acetoxylation, 1,2-diacetoxylation and 1,2,3-triacetoxylation have been realized, accompanied by controllable remote alkenylation. This method enables available terminal olefins from petrochemical feedstocks to be readily converted into unsaturated alcohols and polyalcohols and particularly into different monosaccharides and C-glycosides.

Automated summary

In this study, a palladium-catalyzed aerobic oxidative method was developed for the multi-site programmable functionalization of terminal olefins. The reaction sequence between alkene isomerization and oxidative functionalization was controlled, and a variety of functionalized products were obtained, including unsaturated alcohols, polyalcohols, monosaccharides, and C-glycosides.