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Alkyl−(Hetero)Aryl Bond Formation via Decarboxylative Cross‐Coupling: A Systematic Analysis
Author(s) -
Sandfort Frederik,
O'Neill Matthew J.,
Cornella Josep,
Wimmer Laurin,
Baran Phil S.
Publication year - 2017
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.201612314
Subject(s) - aryl , negishi coupling , alkyl , chemistry , halide , coupling reaction , amide , organic chemistry , combinatorial chemistry , aryl halide , catalysis
Suzuki, Negishi, and Kumada couplings are some of the most important reactions for the formation of skeletal C−C linkages. Their widespread use to forge bonds between two aromatic rings has enabled every branch of chemical science. The analogous union between alkyl halides and metallated aryl systems has not been as widely employed due to the lack of commercially available halide building blocks. Redox‐active esters have recently emerged as useful surrogates for alkyl halides in cross‐coupling chemistry. Such esters are easily accessible through reactions between ubiquitous carboxylic acids and coupling agents widely used in amide bond formation. This article features an amalgamation of in‐house experience bolstered by approximately 200 systematically designed experiments to accelerate the selection of ideal reaction conditions and activating agents for the cross‐coupling of primary, secondary, and tertiary alkyl carboxylic acids with both aryl and heteroaryl organometallic species.