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1. 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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2. 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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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. Protocol for Palladium/N-Heterocyclic Carbene-Catalyzed Suzuki–Miyaura Cross-Coupling of Amides by N–C(O) Activation

   https://doi.org/10.1055/s-0040-1705956  

   Lei, Peng ; Li, Guangchen ; Ling, Yun ; An, Jie ; Nolan, Steven P. ; Szostak, Michal ( January 2021 , Synthesis)

   null (Ed.)

   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. 

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5. 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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