Copper-catalyzed transfer methylenation via C(sp3)-C(sp3) bond cleavage of alcohols

• Published in: ORGANIC CHEMISTRY FRONTIERS Vol. 9; no. 23; pp. 6547 - 6555
• Main Authors: Hong, Chuan-Ming, Zhuang, Xin, Luo, Zhen, Xiong, Si-Qi, Liu, Zheng-Qiang, Li, Qing-Lin, Zou, Fei-Fei, Li, Qing-Hua, Liu, Tang-Lin
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 22.11.2022; Royal Society of Chemistry
• Subjects: Alcohols; Carbonyl compounds; Carbonyls; Chemistry; Chemistry, Organic; Cleavage; Copper; Covalent bonds; Cyano groups; Esters; Functional groups; Functional materials; Hydrogen bonds; Organic chemistry; Physical Sciences; Science & Technology; Substrates; KETONES; HOMOALLYL ALCOHOLS; RETRO-ALDOL REACTION; BORROWING HYDROGEN; ALKYLATION; COUPLING REACTION; ARYL HALIDES; C-C; ALLYL TRANSFER; ALDEHYDES
• ISSN: 2052-4129; 2052-4110; 2052-4110
• DOI: 10.1039/d2qo01373h

Transfer hydrogenation between alcohols and carbonyl compounds via C-H bond cleavage is well known, whereas transfer hydrocarbylation remains a challenge due to the cleavage of the unactivated C-C bond. Herein, we disclose a transfer methylenation approach towards various secondary and tertiary alcohols from abundant chemical feedstocks. To the best of our knowledge, this is a de novo report of transfer methylenation via copper-catalyzed beta-carbon elimination to cleave the C(sp(3))-C(sp(3)) bond of tertiary alcohols. This reaction features a broad substrate scope and good functional group tolerance towards sensitive functional groups (carboxylic esters, cyano group, etc.) and can be scaled up, making it an environmentally friendly and step-economical procedure. Meanwhile, the catalytic system exhibits high reactivity (up to 400 TON), and also allows for the late-stage functionalization of a series of bioactive and functional material molecules. Mechanistic studies indicate that the reaction involves a copper-alkoxide-pyridine intermediate.