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1. 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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2. Synthesis of Amides by Transamidation and Amidation of Activated Amides and Esters

   Li, Guangchen; Szostak, Michal (January 2020, Science of synthesis)

   This chapter provides a summary of the recent advances in direct transamidation and amidation reactions of activated amides and esters via transition- metal-catalyzed and transition-metal-free C(acyl)–N and C(acyl)–O bond cleavage as a new disconnection for the synthesis of amide bonds. 

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3. Transamidation of thioamides with nucleophilic amines: thioamide N–C(S) activation by ground-state-destabilization

   https://doi.org/10.1039/D2OB00412G  

   Zhang, Jin; Zhao, Hui; Li, Guangchen; Zhu, Xinhao; Shang, Linqin; He, Yang; Liu, Xin; Ma, Yangmin; Szostak, Michal (January 2022, Organic & Biomolecular Chemistry)

   Thioamides are ‘single-atom’ isosteres of amide bonds that have found broad applications in organic synthesis, biochemistry and drug discovery. In this New Talent themed issue, we present a general strategy for activation of N–C(S) thioamide bonds by ground-state-destabilization. This concept is outlined in the context of a full study on transamidation of thioamides with nucleophilic amines, and relies on (1) site-selective N -activation of the thioamide bond to decrease resonance and (2) highly chemoselective nucleophilic acyl addition to the thioamide CS bond. The follow-up collapse of the tetrahedral intermediate is favored by the electronic properties of the amine leaving group. The ground-state-destabilization concept of thioamides enables weakening of the N–C(S) bond and rationally modifies the properties of valuable thioamide isosteres for the development of new methods in organic synthesis. We fully expect that in analogy to the burgeoning field of destabilized amides introduced by our group in 2015, the thio amide bond ground-state-destabilization activation concept will find broad applications in various facets of chemical science, including metal-free, metal-catalyzed and metal-promoted reaction pathways. 

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4. 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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5. N-Acylsuccinimides: twist-controlled, acyl-transfer reagents in Suzuki-Miyaura cross-coupling by N-C amide bond activation

   Osumi, Yuki; Liu, Chengwei; Szostak, Michal (October 2017, Organic & biomolecular chemistry)

   The palladium-catalyzed Suzuki-Miyaura cross-coupling of Nacylsuccinimides as versatile acyl-transfer reagents via selective amide N–C bond cleavage is reported. The method is user-friendly since it employs commercially-available, air-stable reagents and catalysts. The cross-coupling is enabled by half-twist of the amide bond in N-acylsuccinimides. These highly effective, crystalline acyltransfer reagents present major advantages over perpendicularly twisted N-acylglutarimides, including low price of the succinimide activating ring, selective metal insertion under redox neutral conditions and high stability of the amide bond towards reaction conditions. Mechanistic studies indicate that oxidative addition is the rate limiting step in this widely applicable protocol. 

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