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1. 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

   https://doi.org/10.3390/molecules26010188  

   Buchspies, Jonathan; Rahman, Md. Mahbubur; Szostak, Michal (January 2021, Molecules)

   null (Ed.)

   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. 

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2. Structures and energetic properties of 4-halobenzamides

   https://doi.org/10.1107/S2053229618013463  

   Piontek, Aleksandra; Bisz, Elwira; Dziuk, Błażej; Szostak, Roman; Szostak, Michal (November 2018, Acta Crystallographica Section C Structural Chemistry)

   The amide bond represents one of the most fundamental functional groups in chemistry. The properties of amides are defined by amidic resonance (n N →π* C=O conjugation), which enforces planarity of the six atoms comprising the amide bond. Despite the importance of 4-halo-substituted benzamides in organic synthesis, molecular interactions and medicinal chemistry, the effect of 4-halo-substitution on the properties of the amide bond in N , N -disubstituted benzamides has not been studied. Herein, we report the crystal structures and energetic properties of a full series of 4-halobenzamides. The structures of four 4-halobenzamides (halo = iodo, bromo, chloro and fluoro) in the N -morpholinyl series have been determined, namely 4-[(4-halophenyl)carbonyl]morpholine, C 11 H 12 X NO 2 , for halo = iodo ( X = I), bromo ( X = Br), chloro ( X = Cl) and fluoro ( X = F). Computations have been used to determine the effect of halogen substitution on the structures and resonance energies. 4-Iodo- N -morpholinylbenzamide crystallized with a significant distortion of the amide bond (τ + χ N = 33°). The present study supports the correlation between the Ar—C(O) axis twist angle and the twist angle of the amide N—C(O) bond. Comparison of resonance energies in synthetically valuable N -morpholinyl and N -piperidinyl amides demonstrates that the O atom of the morpholinyl ring has a negligible effect on amidic resonance in the series. 

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3. Non-Classical Amide Bond Formation: Transamidation and Amidation of Activated Amides and Esters by Selective N–C/O–C Cleavage

   https://doi.org/10.1055/s-0040-1707101  

   Li, Guangchen; Szostak, Michal (January 2020, Synthesis)

   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. 

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4. Transition‐Metal‐Free Activation of Amides by N−C Bond Cleavage

   https://doi.org/10.1002/tcr.201900072  

   Li, Guangchen; Szostak, Michal (December 2019, The Chemical Record)

   Abstract The amide bond N−C activation represents a powerful strategy in organic synthesis to functionalize the historically inert amide linkage. This personal account highlights recent remarkable advances in transition‐metal‐free activation of amides by N−C bond cleavage, focusing on both (1) mechanistic aspects of ground‐state‐destabilization of the amide bond enabling formation of tetrahedral intermediates directly from amides with unprecedented selectivity, and (2) synthetic utility of the developed transformations. Direct nucleophilic addition to amides enables a myriad of powerful methods for the formation of C−C, C−N, C−O and C−S bonds, providing a straightforward and more synthetically useful alternative to acyl‐metals. 

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5. Suzuki–Miyaura Cross-Coupling of Amides Using Well-Defined, Air- and Moisture-Stable Nickel/NHC (NHC = N-Heterocyclic Carbene) Complexes

   https://doi.org/10.3390/catal10040372  

   Buchspies, Jonathan; Rahman, Md. Mahbubur; Szostak, Michal (April 2020, Catalysts)

   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. 

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