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Mechanistic Study of Suzuki–Miyaura Cross‐Coupling Reactions of Amides Mediated by [Pd(NHC)(allyl)Cl] Precatalysts
Author(s) -
Li Guangchen,
Lei Peng,
Szostak Michal,
CasalsCruañas Eric,
Poater Albert,
Cavallo Luigi,
Nolan Steven P.
Publication year - 2018
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201800511
Subject(s) - steric effects , chemistry , amide , ligand (biochemistry) , catalysis , catalytic cycle , isopropyl , coupling reaction , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , biochemistry , receptor
We report a combined experimental and computational investigation of the Suzuki–Miyaura cross‐coupling of amides enabled by [Pd(NHC)(allyl)Cl] precatalysts. Most crucially, mechanistic details pertaining to the Pd 0 /NHC catalytic cycle were elucidated by computational methods. Mechanistic insights shed light on the role of each ligand about the metal. Sterics play a key role in the initial activation of the catalyst. As a key insight, we have shown that water participates in the activation of the Pd‐NHC catalytic system. Easier activation has led to effect room temperature cross‐coupling of a broad range of amides through selective N−C bond scission under the mildest conditions reported to date. The use of sterically hindered [Pd(IPr*)(cin)Cl] reported herein for the first time in the amide cross‐coupling indicates that increasing flexible steric bulk of the isopropyl wingtip groups of the NHC ligand provides a modular scaffold for promoting amide cross‐coupling in high yields. The precatalytic pathway involving both NHC ligands as well as the catalytic cycle beginning from the Pd 0 species are discussed. The mechanistic details provide insight into the amide bond twist (distortion) that leads to N−C cross‐coupling reactions and is required for the efficient N−C bond activation.