Organic Letters
Letter
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Scheme 1. Sequential Cross-Coupling of 1° Amides
In conclusion, we have reported a new method for highly
chemoselective, palladium-NHC-catalyzed, direct cross-
coupling between B-sp3-alkyl reagents and activated amides
by N−C acyl cleavage. This protocol is compatible with
various amides, including challenging primary amides after
direct and site-selective N,N-di-Boc activation and sensitive N-
cyclic amides. The method delivers chemoselective alkylation
products of amides that are inaccessible by applying strong
organometallic reagents. We have further demonstrated the
utility of the method in sequential C(sp2)−C(sp2)/C(sp2)−
C(sp3) cross-couplings employing amides derived from
common primary amide bonds. Further studies will focus on
optimization of the catalyst system and reaction parameters to
expand the substrate scope and mechanistic investigations to
facilitate further reaction development.
(6) For representative tandem coupling, see:Walker, J. A.;
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2017, 139, 10228 and references cited therein.
(7) For a biomimetic esterification, see: (a) Wybon, C. C. D.;
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Maes, B. U. W. ACS Catal. 2018, 8, 203. For a Co-catalyzed
esterification, see: (b) Bourne-Branchu, Y.; Gosmini, C.; Danoun, G.
Chem. - Eur. J. 2017, 23, 10043. For a Cr-catalyzed N−C activation,
see: (c) Chen, C.; Liu, P.; Luo, M.; Zeng, X. ACS Catal. 2018, 8,
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(8) For select examples of metal-free acyl N−C bond activation, see:
(a) Liu, Y.; Shi, S.; Achtenhagen, M.; Liu, R.; Szostak, M. Org. Lett.
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(9) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815.
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ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Procedures and analytical data (PDF)
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
(11) Meng, G.; Shi, S.; Lalancette, R.; Szostak, R.; Szostak, M. J. Am.
Chem. Soc. 2018, 140, 727.
(12) Trost, B. M.; Fleming, I. Comprehensive Organic Synthesis;
ACKNOWLEDGMENTS
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Rutgers University and the NSF (CAREER CHE-1650766)
are gratefully acknowledged for support. G.M. thanks the
Graduate-School-Newark for a Dissertation Fellowship.
Pergamon Press: Oxford, 1991.
(13) (a) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111,
1417. (b) Giri, R.; Thapa, S.; Kafle, A. Adv. Synth. Catal. 2014, 356,
1395.
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