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Synthesis 2021; 53(04): 682-687
DOI: 10.1055/s-0040-1705956
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Protocol for Palladium/N-Heterocyclic Carbene-Catalyzed Suzuki–Miyaura Cross-Coupling of Amides by N–C(O) Activation

Peng Lei‡
a   College of Plant Protection, Northwest A & F University, Yangling, Shaanxi 712100, P. R. of China   Email: peng.lei@nwafu.edu.cn
b   Department of Applied Chemistry, China Agricultural University, Beijing 100193, P. R. of China
c   Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, USA   Email: michal.szostak@rutgers.edu
,
Guangchen Li‡
c   Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, USA   Email: michal.szostak@rutgers.edu
,
Yun Ling
b   Department of Applied Chemistry, China Agricultural University, Beijing 100193, P. R. of China
,
Jie An 
d   Department of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China
,
Steven P. Nolan
e   Department of Chemistry and Center for Sustainable Chemistry, Ghent University, Krijgslaan 281, S-3, 9000 Ghent, Belgium
,
Michal Szostak  ∗
c   Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, USA   Email: michal.szostak@rutgers.edu
› Author AffiliationsRutgers University and the NSF (CAREER CHE-1650766) are gratefully acknowledged for support. Supplement funding for this project was provided by the Rutgers University – Newark Chancellor’s Research Office. The Bruker 500 MHz spectrometer was supported by the NSF-MRI grant (CHE-1229030). P.L. thanks Natural Science Basic Research Program of Shaanxi (Program No. 2020JQ-238), the Young Talent Fund of University Association for Science and Technology in Shaanxi (Program No. 2019-02-02). We gratefully acknowledge VLAIO (SBO project CO2PERATE), the Special Research Fund (BOF) of Ghent University is also acknowledged for starting and project grants to S.P.N. We thank the National Natural Science Foundation of China (No. 22077137, Y.L.).
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Abstract

Amides are among the most important and ubiquitous functional groups in organic chemistry and process development. In this Practical Synthetic Procedure, a protocol for the Suzuki–Miyaura cross-coupling of amides by selective N–C(O) bond activation catalyzed by commercially available, air- and moisture-stable palladium/N-heterocyclic carbene (NHC) complexes is described. The procedure described involves [Pd(IPr)(cin)Cl] [IPr = 2,6-(diisopropylphenyl)imidazol-2-ylidene, cin = cinnamyl] at 0.10 mol% at room temperature and is performed on decagram scale. Furthermore, a procedure for the synthesis of amide starting materials is accomplished via selective N-tert-butoxycarbonylation, which is the preferred method over N-acylation. The present protocol carries advantages of operational simplicity, commercial availability of catalysts, and excellent conversions at low catalyst loadings. The method is generally useful for activation of N–C(O) amide bonds in a broad spectrum of amide precursors. The protocol should facilitate the implementation of amide cross-coupling reactions.

Key words

amides - N–C(O) activation - N-heterocyclic carbenes (NHCs) - Suzuki–Miyaura cross-coupling - Pd(II)–NHCs - [Pd(IPr)(cin)Cl]

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1705956.
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Publication History

Received: 28 August 2020

Accepted after revision: 26 September 2020

Article published online:
12 November 2020

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