Palladium-NHC (NHC = N‑heterocyclic Carbene)-Catalyzed Suzuki–Miyaura Cross-Coupling of Alkyl Amides

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 c...

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Published in:ACS catalysis 2022-02, Vol.12 (4), p.2426-2433
Main Authors: Wang, Chang-An, Rahman, Md. Mahbubur, Bisz, Elwira, Dziuk, Błażej, Szostak, Roman, Szostak, Michal
Format: Article
Language:English
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Summary: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.
ISSN:2155-5435
2155-5435
DOI:10.1021/acscatal.1c05738