Cobalt-Catalyzed Cross-Coupling of α-Bromo Amides with Grignard Reagents

Abstract

A cobalt-catalyzed cross-coupling between α-bromo amides and Grignard reagents is disclosed. The reaction is general and allows access to a large variety of α-aryl and β,γ-unsaturated amides. Some mechanistic investigations have been undertaken to determine the nature of the intermediate species.

The Fascinating Chemistry of α‐Haloamides

“…In 2017 a cobalt‐catalyzed cross‐coupling between α‐bromoamides and alkenyl Grignard reagents was disclosed by Cossy and co‐workers (Scheme ) …”

“…α‐Bromo tertiary amides A cross‐coupled with aryl Grignard reagents B following a protocol reaction developed by Cossy and co‐workers that used an equimolar mixture of CoCl 2 and Xantphos as the optimal catalyst system in THF (Scheme ) …”

“…In 2017 a cobalt-catalyzed cross-coupling between αbromoamides and alkenyl Grignard reagents was disclosed by Cossy and co-workers (Scheme 115). [140] The alkenylation process providing β,γ-unsaturated amides entailed reacting the nucleophilic and the elecrophilic partners in THF at À 40°C in the presence of CoCl 2 and the bidentate diphosphine ligand Xantphos (Scheme 115). N,N-Dibenzyl-3methyl-2-bromo butanamide A cross-coupled with alkenyl Grignard reagents B (2 equiv.)…”

“…α-Bromo tertiary amides A cross-coupled with aryl Grignard reagents B following a protocol reaction developed by Cossy and co-workers that used an equimolar mixture of CoCl 2 and Xantphos as the optimal catalyst system in THF (Scheme 134). [140] Optimized conditions for the cross-coupling products C formation, effective also on a gram scale, entailed a B/A ratio of 2 : 1 and reaction temperatures in a range from 0°C to rt; higher than the one in the related cobalt-catalyzed α-alkenylations (see Section 8.). Various substituents were tolerated at para and metha positions of the phenyl nucleus in the Grignard reagents, whereas an ortho methyl led the yield to drop.…”

Effect of Fluorination on Skin Sensitization Potential and Fragrant Properties of Cinnamyl Compounds

“…Known compounds 1 -3b have already been synthesized in our laboratories by Gu erin et al using the following reaction sequence: [11] Ethyl (Z)-2-fluoro-3phenylacrylate (3b) was obtained in 60% yield as a single double bond isomer by diethylzinc mediated olefination of benzaldehyde with ethyl dibromofluoroacetate (Scheme 1). [12] Reduction of ester 3b by LiBH 4 in tetrahydrofuran (THF) afforded the alcohol 2b in quantitative yield. [13] This latter compound was then oxidized by IBX (2-iodoxybenzoic acid) to give the desired 2-fluorocinnamaldehyde (1b) in 85% yield, as already published by Wheeler et al [14] Ethyl (Z)-3-fluoro-3-phenylacrylate (3c) was synthesized by the addition of silver fluoride to ethyl phenylpropiolate as reported by Jiang and co-workers, and is described in Scheme 2.…”