skip to main content

Title: Transamidation of Amides and Amidation of Esters by Selective N–C(O)/O–C(O) Cleavage Mediated by Air- and Moisture-Stable Half-Sandwich Nickel(II)–NHC Complexes
The formation of amide bonds represents one of the most fundamental processes in organic synthesis. Transition-metal-catalyzed activation of acyclic twisted amides has emerged as an increasingly powerful platform in synthesis. Herein, we report the transamidation of N-activated twisted amides by selective N–C(O) cleavage mediated by air- and moisture-stable half-sandwich Ni(II)–NHC (NHC = N-heterocyclic carbenes) complexes. We demonstrate that the readily available cyclopentadienyl complex, [CpNi(IPr)Cl] (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene), promotes highly selective transamidation of the N–C(O) bond in twisted N-Boc amides with non-nucleophilic anilines. The reaction provides access to secondary anilides via the non-conventional amide bond-forming pathway. Furthermore, the amidation of activated phenolic and unactivated methyl esters mediated by [CpNi(IPr)Cl] is reported. This study sets the stage for the broad utilization of well-defined, air- and moisture-stable Ni(II)–NHC complexes in catalytic amide bond-forming protocols by unconventional C(acyl)–N and C(acyl)–O bond cleavage reactions.
Authors:
; ;
Award ID(s):
1650766
Publication Date:
NSF-PAR ID:
10224916
Journal Name:
Molecules
Volume:
26
Issue:
1
Page Range or eLocation-ID:
188
ISSN:
1420-3049
Sponsoring Org:
National Science Foundation
More Like this
  1. The Pd–NHC-catalyzed acyl-type Buchwald–Hartwig cross-coupling of amides by N–C(O) cleavage (transamidation) provides a valuable alternative to the classical methods for amide synthesis. Herein, we report a combined experimental and computational study of the Buchwald–Hartwig cross-coupling of amides using well-defined, air- and moisture-stable [Pd(NHC)(allyl)Cl] precatalysts. Most crucially, we present a comprehensive evaluation of a series of distinct Pd( ii )–NHC precatalysts featuring different NHC scaffolds and throw-away ligands for the synthesis of functionalized amides that are not compatible with stoichiometric transition-metal-free transamidation methods. Furthermore, we present evaluation of the catalytic cycle by DFT methods for a series of different Pd( ii )–NHC precatalysts. The viability of accessing NHC-supported acyl-palladium( ii ) amido complexes will have implications for the design and development of cross-coupling methods involving stable amide electrophiles.
  2. In this Special Issue on N-Heterocyclic Carbenes and Their Complexes in Catalysis, we report the first example of Suzuki–Miyaura cross-coupling of amides catalyzed by well-defined, air- and moisture-stable nickel/NHC (NHC = N-heterocyclic carbene) complexes. The selective amide bond N–C(O) activation is achieved by half-sandwich, cyclopentadienyl [CpNi(NHC)Cl] complexes. The following order of reactivity of NHC ligands has been found: IPr > IMes > IPaul ≈ IPr*. Both the neutral and the cationic complexes are efficient catalysts for the Suzuki–Miyaura cross-coupling of amides. Kinetic studies demonstrate that the reactions are complete in < 1 h at 80 °C. Complete selectivity for the cleavage of exocyclic N-acyl bond has been observed under the experimental conditions. Given the utility of nickel catalysis in activating unreactive bonds, we believe that well-defined and bench-stable [CpNi(NHC)Cl] complexes will find broad application in amide bond and related cross-couplings of bench-stable acyl-electrophiles.
  3. 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.
  4. In the past several years, tremendous advances have been made in non-classical routes for amide bond formation that involve transamidation and amidation reactions of activated amides and esters. These new methods enable the formation of extremely valuable amide bonds via transition-metal- catalyzed, transition-metal-free or metal-free pathways by exploiting chemoselective acyl C–X (X = N, O) cleavage under mild conditions. In a broadest sense, these reactions overcome the formidable challenge of activating C–N/C–O bonds of amides or esters by rationally tackling nN→π*C=O delocalization in amides and nO→π*C=O donation in esters. In this account, we summarize the recent remarkable advances in the development of new methods for the synthesis of amides with a focus on (1) transition-metal/NHC- catalyzed C–N/C–O bond activation, (2) transition-metal-free highly selective cleavage of C–N/C–O bonds, (3) the development of new acyl-transfer reagents, and (4) other emerging methods.
  5. The Suzuki-Miyaura cross-coupling has been widely recognized as one of the most important methods for the construction of C–C bonds. However, in contrast to traditional aryl halide or pseudohalide electrophiles, coupling reactions with unactivated C–N and C–O electrophiles have proven significantly more challenging. Here we report the first general palladium-catalyzed Suzuki-Miyaura cross-coupling of both common amides and aryl esters through the selective cleavage of the C–N and C–O bonds under exceedingly mild conditions. Notably, for the first time we demonstrate selective C(acyl)– N and C(acyl)–O cleavage/cross-coupling under the same reaction conditions. The reaction uses a commercially available, bench-stable and operationally-convenient (n3-1-t-Bu-indenyl)Pd(IPr)(Cl) precatalyst. Furthermore, we demonstrate that the reactivity of generic amides and aryl esters can be correlated with barriers to isomerization around the C(acyl)–X (X = N, O) bond, thus providing a blueprint for the development of a broad range of novel coupling reactions of ester and amide electrophiles by the selective activation of C–O and C–N bonds.