Direct and selective functionalization of hydrocarbon chains is a fundamental problem in synthetic chemistry. Conventional functionalization of C=C double bonds and C(sp3)–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(sp3)–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.
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We are grateful for financial support provided by the National Natural Science Foundation of China (Nos 21620102003, 21831005 and 21991112 to W.Z.), the National Key R&D Program of China (No. 2018YFE0126800 to W.Z.) and the Shanghai Municipal Education Commission (No. 201701070002E00030 to W.Z.). We thank the Instrumental Analysis Center of SJTU for characterization experiments. We are grateful to Q. Ge and C. Xu for their contribution concerning the purification of compounds.
The authors declare no competing interests.
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Supplementary Figs. 1–28, Tables 1–6, synthesis and characterization data, supplementary discussion, computational and procedural details, NMR spectra and references.
Supplementary Data 1
Cartesian coordinates (x,y,z) and coupling constants.
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Wu, Z., Meng, J., Liu, H. et al. Multi-site programmable functionalization of alkenes via controllable alkene isomerization. Nat. Chem. (2023). https://doi.org/10.1038/s41557-023-01209-x