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1. 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)

   Abstract 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. magnified image 

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2. Palladium-catalyzed decarbonylative Suzuki–Miyaura cross-coupling of amides by carbon–nitrogen bond activation

   https://doi.org/10.1039/c9sc03169c  

   Zhou, Tongliang; Ji, Chong-Lei; Hong, Xin; Szostak, Michal (October 2019, Chemical Science)

   Palladium-catalyzed Suzuki–Miyaura cross-coupling or aryl halides is widely employed in the synthesis of many important molecules in synthetic chemistry, including pharmaceuticals, polymers and functional materials. Herein, we disclose the first palladium-catalyzed decarbonylative Suzuki–Miyaura cross-coupling of amides for the synthesis of biaryls through the selective activation of the N–C(O) bond of amides. This new method relies on the precise sequence engineering of the catalytic cycle, wherein decarbonylation occurs prior to the transmetallation step. The reaction is compatible with a wide range of boronic acids and amides, providing valuable biaryls in high yields (>60 examples). DFT studies support a mechanism involving oxidative addition, decarbonylation and transmetallation and provide insight into high N–C(O) bond activation selectivity. Most crucially, the reaction establishes the use of palladium catalysis in the biaryl Suzuki–Miyaura cross-coupling of the amide bond and should enable the design of a wide variety of cross-coupling methods in which palladium rivals the traditional biaryl synthesis from aryl halides and pseudohalides. 

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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. N-Acyl-5,5-Dimethylhydantoins: Mild Acyl-Transfer Reagents for the Synthesis of Ketones using Pd–PEPPSI or Pd/Phosphine Catalysis

   https://doi.org/10.1021/acs.oprd.0c00054  

   Wang, Chang-An; Liu, Chengwei; Szostak, Michal (April 2020, Organic Process Research & Development)

   N-Acyl-hydantoins have emerged as novel acyl transfer reagents for the synthesis of ketones via selective N–C(O) cleavage. Herein, we report two new protocols for the cross-coupling of N-acyl-5,5-dimethylhydantoins using versatile and readily accessible Pd–PEPPSI or Pd/phosphine catalysts. The acyl Suzuki reactions afford biaryl ketones in good to excellent yields under operationally-simple conditions using commercially-available, bench- and air-stable twisted N-acyl-hydantoins as acyl donors. The method complements and expands on the previous protocol for the cross-coupling of N-acyl-hydantoins (Org. Process Res. Dev. 2018, 22, 1188). 

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5. Thioesterification and Selenoesterification of Amides via Selective N–C Cleavage at Room Temperature: N–C(O) to S/Se–C(O) Interconversion

   https://doi.org/10.1055/s-0039-1690055  

   Rahman, Md. Mahbubur; Li, Guangchen; Szostak, Michal (March 2020, Synthesis)

   The direct nucleophilic addition to amides represents an attractive methodology in organic synthesis that tackles amidic resonance by ground-state destabilization. This approach has been recently accomplished with carbon, nitrogen and oxygen nucleophiles. Herein, we report an exceedingly mild method for the direct thioesterification and selenoesterification of amides by selective N–C(O) bond cleavage in the absence of transition metals. Acyclic amides undergo N–C(O) to S/Se–C(O) interconversion to give the corresponding thioesters and selenoesters in excellent yields at room temperature via a tetrahedral intermediate pathway (cf. an acyl metal). 

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