Premium
Site‐Selective Alkoxylation of Benzylic C−H Bonds by Photoredox Catalysis
Author(s) -
Lee Byung Joo,
DeGlopper Kimberly S.,
Yoon Tehshik P.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201910602
Subject(s) - chemoselectivity , chemistry , nucleophile , photoredox catalysis , combinatorial chemistry , catalysis , alcohol , alkoxy group , radical , solvent , alcohol oxidation , photocatalysis , functional group , molecule , organic synthesis , photochemistry , organic chemistry , alkyl , polymer
Methods that enable the direct C−H alkoxylation of complex organic molecules are significantly underdeveloped, particularly in comparison to analogous strategies for C−N and C−C bond formation. In particular, almost all methods for the incorporation of alcohols by C−H oxidation require the use of the alcohol component as a solvent or co‐solvent. This condition limits the practical scope of these reactions to simple, inexpensive alcohols. Reported here is a photocatalytic protocol for the functionalization of benzylic C−H bonds with a wide range of oxygen nucleophiles. This strategy merges the photoredox activation of arenes with copper(II)‐mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C−O bonds with high site selectivity, chemoselectivity, and functional‐group tolerance using only two equivalents of the alcohol coupling partner. This method enables the late‐stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential applications in synthesis and medicinal chemistry.