Letter pubs.acs.org/OrgLett
A General Method for Two-Step Transamidation of Secondary Amides Using Commercially Available, Air- and Moisture-Stable Palladium/NHC (N‑Heterocyclic Carbene) Complexes Guangrong Meng, Peng Lei,† and Michal Szostak* Department of Chemistry, Rutgers University, 73 Warren Street, Newark, New Jersey 07102, United States S Supporting Information *
ABSTRACT: The first general method is reported for transamidation of secondary carboxamides catalyzed by PdNHC (NHC = N-heterocyclic carbene) complexes. Commercially available, air- and moisture-stable (NHC)Pd(R-allyl)Cl complexes can effect C−N cross-coupling of a wide range of N-Boc and N-Ts amides, obtained by selective amide Nfunctionalization, with non-nucleophilic anilines and sterically hindered amines in very good yields. The first use of versatile Pd-NHC complexes as catalysts is represented for transitionmetal-catalyzed C(acyl)−N amination of amides by N−C activation.
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ransamidation of the carbon−nitrogen bond of secondary carboxamides represents a long-standing challenge in catalysis due to kinetic and thermodynamic barriers for the amide N−C bond activation and thermoneutral exchange.1−4 Secondary carboxamides are essential structures in proteins5 and synthetic polyamides.6,7 Moreover, secondary carboxamides represent a fundamental functional group in organic synthesis.8 Very few examples of the selective transamidation of secondary carboxamides have been reported.3 In 2016, Garg and co-workers developed Ni-catalyzed transamidation of secondary carboxamides (Figure 1A).9 This is the first catalytic system that provides a general route to functionalized amides by transamidation of the secondary carboxamide group by N−
Figure 2. (A) Proposed mechanism for two-step transamidation. (B) Structures of carbene ligands and well-defined Pd-NHC catalysts. Dipp = 2,6-diisopropylphenyl; Mes = mesityl; Cy = cyclohexyl.
C cross-coupling. Very recently, Newman and co-workers reported amide bond formation from esters catalyzed by PdNHC (Figure 1B).10 Herein, we report the first general method for transamidation of secondary carboxamides catalyzed by PdNHC complexes (Figure 1C). The reported reaction represents Figure 1. Transition-metal-catalyzed cross-coupling reactions of amides and esters with amines: previous (A−B) and (C) this work. © XXXX American Chemical Society
Received: March 17, 2017
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DOI: 10.1021/acs.orglett.7b00796 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters Table 1. Optimization of the Reaction Conditionsa
entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14c 15
catalyst
ligand
Pd(OAc)2 PPh3 Pd(OAc)2 PCy3HBF4 Pd(OAc)2 P(o-Tol)3 Pd(OAc)2 IPrHCl Pd(OAc)2 IMesHCl Pd(OAc)2 ICyHBF4 (IPr)Pd(cinnamyl)Cl (SIPr)Pd(cinnamyl)Cl (IPr)Pd(allyl)Cl (IPr)Pd(cinnamyl)Cl (IPr)Pd(cinnamyl)Cl (IPr)Pd(cinnamyl)Cl (IPr)Pd(cinnamyl)Cl (IPr)Pd(cinnamyl)Cl −
Table 2. Pd-NHC-Catalyzed Transamidationa,b
base
t (°C)
yield (%)b
K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 NaOt-Bu KOt-Bu Cs2CO3 K2CO3 K2CO3 K2CO3
110 110 110 110 110 110 110 110 110 110 110 110 60 110 110
