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Pd/NHC sequentially catalyzed atroposelective synthesis of planar-chiral macrocycles.

Chem Sci

November 2024

School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorous Chemistry and Chemical Biology, Ministry of Education, Tsinghua University Beijing 100084 China

Planar-chiral macrocycles play a pivotal role in host-guest chemistry and drug discovery. However, compared with the synthesis of other types of chiral compounds, the asymmetric construction of planar-chiral macrocycles still remains a forbidding challenge. Herein, we report a sequential palladium and N-heterocyclic carbene catalysis to build planar-chiral macrocycles.

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Article Synopsis
  • Palladium-catalyzed cross-coupling reactions are crucial in various fields like pharmaceuticals and materials science due to their ability to form C-C and C-X bonds selectively and efficiently.
  • The development of new ligands and precatalysts, especially Pd(II)-N-heterocyclic carbene complexes, enhances reaction selectivity and reactivity while maintaining stability under mild conditions.
  • The latest innovation includes the highly reactive chloro dimers of Pd(NHC) complexes, which can be easily synthesized in a one-pot process and are stable yet effective in catalyzing reactions.
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Experimental Evidence for Zerovalent Pd(NHC) as a Competent Catalyst in C-N Cross-Coupling (NHC = DiMeIHept).

J Am Chem Soc

October 2024

Centre for Catalysis Research and Innovation (CCRI), Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.

Use of the branched N-heterocyclic carbene (NHC) ligand 1,3-bis(2,6-bis(3-methyl-1-(2-methylpropyl)butyl)phenyl)-4,5-dichloro-1,3-dihydro-2-imidazole-2-ylidene (DiMeIHept) facilitated the stabilization of several relevant intermediates for Pd(NHC)-catalyzed C-N cross-coupling reactions. Complexes [Pd(DiMeIHept)](μ-N), [Pd(DiMeIHept)](μ-η-1,2-η-4,5-CH), and Pd(DiMeIHept)(pyridine), representing zerovalent Pd(NHC) bearing labile ligands, were isolated and structurally characterized, along with divalent PdCl(Ph)(DiMeIHept) and PdCl(Ph)(DiMeIHept)(-propylamine). The former is a 14-electron Pd complex, which is stable under air and chromatography on silica gel or neutral alumina.

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Herein, we report a one-pot approach to diarylamines through the reductive homocoupling of nitroaromatics, employing triethylsilane as the reducing agent and Pd/NHC as the catalyst. This method enables nitroaromatics to serve both as electrophilic reagents and as precursors of nucleophilic reagents, allowing for the direct preparation of diarylamines without the need to isolate aromatic primary amines.

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2-Alkylpyridines are a privileged scaffold throughout the realm of organic synthesis and play a key role in natural products, pharmaceuticals, and agrochemicals. Herein, we report the first B-alkyl Suzuki cross-coupling of 2-pyridyl ammonium salts to access functionalized 2-alkylpyridines. The use of well-defined, operationally simple Pd-NHCs permits for an exceptionally broad scope of the challenging B-alkyl C-N cross-coupling with organoboranes containing β-hydrogen, representing a novel method for the discovery of highly sought-after molecules for plant protection.

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