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1. Buchwald–Hartwig cross-coupling of amides (transamidation) by selective N–C(O) cleavage mediated by air- and moisture-stable [Pd(NHC)(allyl)Cl] precatalysts: catalyst evaluation and mechanism

   https://doi.org/10.1039/C9CY02080B  

   Li, Guangchen ; Zhou, Tongliang ; Poater, Albert ; Cavallo, Luigi ; Nolan, Steven P. ; Szostak, Michal ( February 2020 , Catalysis Science & Technology)

   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. 

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2. Suzuki‐Miyaura Cross‐Coupling of Amides using Well‐Defined, Air‐Stable [(PR 3 ) 2 Pd(II)X 2 ] Precatalysts

   https://doi.org/10.1002/adsc.202000122  

   Ma, Siyue ; Zhou, Tongliang ; Li, Guangchen ; Szostak, Michal ( April 2020 , Advanced Synthesis & Catalysis)

   A versatile method for the Suzuki‐Miyaura cross‐coupling of amides using highly active, well‐defined, and air‐stable Pd−phosphine precatalysts is reported. Most notably, the method represents the first example of using practical and operationally‐simple Pd(II)−phosphine precatalysts in the emerging amide bond cross‐coupling manifold. The reactions are efficient at 0.10 mol% loading, furnishing biaryl ketones with high chemoselectivity for N−C(O) bond cleavage. This versatile method enables for the first time to achieve Pd−phosphine‐catalyzed cross‐coupling of amides at ppm loading. This C−N cross‐coupling can be used to efficiently furnish pharmaceutical intermediates by orthogonal Pd‐catalyzed cross‐couplings. We fully expect that operationally‐simple [(PR₃)₂Pd(II)X₂] precatalysts as effective triggers for N−C(O) cross‐coupling will be of broad synthetic and catalytic interest.

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3. N-Acylphthalimides: Efficient Acyl Coupling Reagents in Suzuki–Miyaura Cross-Coupling by N–C Cleavage Catalyzed by Pd–PEPPSI Precatalysts

   https://doi.org/10.3390/catal9020129  

   Rahman, Md. ; Buchspies, Jonathan ; Szostak, Michal ( February 2019 , Catalysts)

   We report a general, highly selective method for Suzuki–Miyaura cross-coupling of N-acylphthalimides via N–C(O) acyl cleavage catalyzed by Pd–PEPPSI-type precatalysts. Of broad synthetic interest, the method introduces N-acylphthalimides as new, bench-stable, highly reactive, twist-controlled, amide-based precursors to acyl-metal intermediates. The reaction delivers functionalized biaryl ketones by acylative Suzuki–Miyaura cross-coupling with readily available boronic acids. Studies demonstrate that cheap, easily prepared, and broadly applicable Pd–PEPPSI-type precatalysts supported by a sterically demanding IPr (1,3-Bis-(2,6-diisopropylphenyl)imidazol-2-ylidene) ancillary ligand provide high yields in this reaction. Preliminary selectivity studies and the effect of Pd–N-heterocyclic carbenes (NHC) complexes with allyl-type throw-away ligands are described. We expect that N-acylphthalimides will find significant use as amide-based acyl coupling reagents and cross-coupling precursors to acyl-metal intermediates. 

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4. Suzuki–Miyaura cross-coupling of amides and esters at room temperature: correlation with barriers to rotation around C–N and C–O bonds

   Lei, Peng ; Meng, Guangrong ; Shi, Shicheng ; Ling, Yun ; An, Jie ; Szostak, Roman ; Szostak, Michal ( August 2017 , Chemical science)

   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. 

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5. 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)

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   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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