化学
酰胺
催化作用
卡宾
位阻效应
钯
电泳剂
偶联反应
组合化学
烷基
药物化学
有机化学
立体化学
作者
Chang‐An Wang,Md. Mahbubur Rahman,Elwira Bisz,Błażej Dziuk,Roman Szostak,Michal Szostak
标识
DOI:10.1021/acscatal.1c05738
摘要
We report the Pd-catalyzed Suzuki–Miyaura cross-coupling of aliphatic amides. Although tremendous advances have been made in the cross-coupling of aromatic amides, C–C bond formation from aliphatic amides by selective N–C(O) cleavage has remained a major challenge. This longstanding problem in Pd catalysis has been addressed herein by a combination of (1) the discovery of N,N-pym/Boc amides as a class of readily accessible amide-based reagents for cross-coupling and (2) steric tuning of well-defined Pd(II)-NHC catalysts for cross-coupling. The methodology is effective for the cross-coupling of an array of 3°, 2°, and 1° aliphatic amide derivatives. The catalyst system is user-friendly, since the catalysts are readily available and are air- and bench-stable. Mechanistic studies strongly support an amide bond twist and external nN → π*C═O/Ar delocalization as a unified enabling feature of N,N-pym/Boc amides in selective N–C(O) bond activation. The method provides a rare example of Pd-NHC-catalyzed cross-coupling of aliphatic acyl amide electrophiles.
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