title: Alkyl-(Hetero)Aryl Bond Formation via Decarboxylative Cross-Coupling: A Systematic Analysis.
abstract: 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.
authors.affiliation: The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Frederik
authors.initials: F
authors.lastname: Sandfort
authors.affiliation: The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: O'Neill
authors.affiliation: The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Josep
authors.initials: J
authors.lastname: Cornella
authors.affiliation: The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Laurin
authors.initials: L
authors.lastname: Wimmer
authors.affiliation: The Scripps Research Institute (TSRI), North Torrey Pines Road, La Jolla, CA, 92037, USA.
authors.forename: Phil S
authors.identifier: 0000-0001-9193-9053
authors.initials: PS
authors.lastname: Baran
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D003653:Decarboxylation; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D000577:Amides; D002264:Carboxylic Acids; D006846:Hydrocarbons, Halogenated; D009942:Organometallic Compounds
keywords: decarboxylative cross-coupling; iron catalysis; nickel catalysis; redox-active esters