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1. 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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2. 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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3. Transamidation of N-acyl-glutarimides with amines

   Liu, Yongmei; Achtenhagen, Marcel; Liu, Ruzhang; Szostak, Michal (February 2018, Organic & biomolecular chemistry)

   The development of new transamidation reactions for the synthesis of amides is an important and active area of research due to the central role of amide linkage in various fields of chemistry. Herein, we report a new method for transamidation of N-acyl-glutarimides with amines under mild, metal-free conditions that relies on amide bond twist to weaken amidic resonance. A wide range of amines and functional groups, including electrophilic substituents that would be problematic in metal-catalyzed protocols, are tolerated under the reaction conditions. Mechanistic experiments implicate the amide bond twist, thermodynamic stability of the tetrahedral intermediate and leaving group ability of glutarimide as factors controlling the reactivity of this process. The method further establishes the synthetic utility of N-acyl-glutarimides as bench-stable, twist-perpendicular, amide-based reagents in acyl-transfer reactions by a metal-free pathway. The origin of reactivity of N-acyl-glutarimides in metal-free and metal-catalyzed processes is discussed and compared. 

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4. 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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5. ¹⁷ O NMR and ¹⁵ N NMR chemical shifts of sterically-hindered amides: ground-state destabilization in amide electrophilicity

   https://doi.org/10.1039/c9cc01402k  

   Pace, Vittorio; Holzer, Wolfgang; Ielo, Laura; Shi, Shicheng; Meng, Guangrong; Hanna, Mina; Szostak, Roman; Szostak, Michal (April 2019, Chemical Communications)

   The structure and spectroscopic properties of the amide bond are a topic of fundamental interest in chemistry and biology. Herein, we report 17 O NMR and 15 N NMR spectroscopic data for four series of sterically-hindered acyclic amides. Despite the utility of 17 O NMR and 15 N NMR spectroscopy, these methods are severely underutilized in the experimental determination of electronic properties of the amide bond. The data demonstrate that a combined use of 17 O NMR and 15 N NMR serves as a powerful tool in assessing electronic effects of the amide bond substitution as a measure of electrophilicity of the amide bond. Notably, we demonstrate that steric destabilization of the amide bond results in electronically-activated amides that are comparable in terms of electrophilicity to acyl fluorides and carboxylic acid anhydrides. 

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