Radical dehydroxylative alkylation of tertiary alcohols by Ti catalysis

Hao Xie, Jiandong Guo, Yu Quan Wang, Ke Wang, Peng Guo, Pei Feng Su, Xiaotai Wang*, Xing Zhong Shu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

Abstract

Deoxygenative radical C−C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report a direct dehydroxylative radical alkylation reaction of tertiary alcohols. This new protocol shows the feasibility of generating tertiary carbon radicals from alcohols and offers an approach for the facile and precise construction of all-carbon quaternary centers. The reaction proceeds with a broad substrate scope of alcohols and activated alkenes. It can tolerate a wide range of electrophilic coupling partners, including allylic carboxylates, aryl and vinyl electrophiles, and primary alkyl chlorides/bromides, making the method complementary to the cross-coupling procedures. The method is highly selective for the alkylation of tertiary alcohols, leaving secondary/primary alcohols (benzyl alcohols included) and phenols intact. The synthetic utility of the method is highlighted by its 10-g-scale reaction and the late-stage modification of complex molecules. A combination of experiments and density functional theory calculations establishes a plausible mechanism implicating a tertiary carbon radical generated via Ti-catalyzed homolysis of the C−OH bond.

Original languageEnglish
Pages (from-to)16787-16794
Number of pages8
JournalJournal of the American Chemical Society
Volume142
Issue number39
DOIs
Publication statusPublished - 30 Sept 2020
Externally publishedYes

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