Chiral amine scaffolds are among the most important building blocks in natural products, drug molecules, and functional materials, which have prompted chemists to focus more on their synthesis. Among the accomplishments in chiral amine synthesis, transition-metal-catalyzed enantioselective C-N cross-coupling is considered one of the most efficient protocols. This approach combines traditional C(sp)-N cross-coupling methods (such as the Buchwald-Hartwig reaction Ullmann-type reaction, and Chan-Evans-Lam reaction), aryliodonium salt chemistry and radical chemistry, providing an attractive pathway to a wide range of structurally diverse chiral amines with high enantioselectivity. This review summarizes the established protocols and offers a comprehensive outlook on the promising enantioselective C-N cross-coupling reaction.
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http://dx.doi.org/10.1039/d4cs00102h | DOI Listing |
Nat Commun
January 2025
Shenzhen Grubbs Institute and Department of Chemistry, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, China.
3-Amino boron dipyrromethenes (BODIPYs) are a versatile class of fluorophores widely utilized in live cell imaging, photodynamic therapy, and fluorescent materials science. Despite the growing demand for optically active BODIPYs, the synthesis of chiral 3-amino-BODIPYs, particularly the catalytic asymmetric version, remains a challenge. Herein, we report the synthesis of boron-stereogenic 3-amino-BODIPYs via a palladium-catalyzed desymmetric C-N cross-coupling of prochiral 3,5-dihalogen-BODIPYs.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry and the Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR 999077, China.
Catalytic enantioselective substitution of the readily available racemic α-halo carbonyl compounds by nitrogen nucleophiles represents one of the most convenient and direct approaches to access enantioenriched α-amino carbonyl compounds. Distinct from the two available strategies involving radicals and enolate ions, herein we have developed a new protocol featuring an electronically opposite way to weaken/cleave the carbon-halogen bond. A suitable chiral anion-based catalyst enables effective asymmetric control over the key positively charged intermediates.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St. Andrews, KY16 9ST, U.K.
The [1,2]-rearrangement of allylic ammonium ylides is traditionally observed as a competitive minor pathway alongside the thermally allowed [2,3]-sigmatropic rearrangement. Concerted [1,2]-rearrangements are formally forbidden, with these processes believed to proceed through homolytic C-N bond fission of the ylide, followed by radical-radical recombination. The challenges associated with developing a catalytic enantioselective [1,2]-rearrangement of allylic ammonium ylides therefore lie in biasing the reaction pathway to favor the [1,2]-reaction product, alongside controlling a stereoselective radical-radical recombination event.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
State key laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, 15 Yu Cai Road, Guilin, 541004, China.
Skeletal editing represents an attractive strategy for adding complexity to a given molecular scaffold in chemical synthesis. Isodesmic reactions provide a complementary skeletal editing approach for the redistribution of chemical bonds in chemical synthesis. However, catalytic enantioselective isodesmic reaction is extremely scarce and enantioselective isodesmic reaction to synthesize atropisomeric compounds is unknown.
View Article and Find Full Text PDFOrg Lett
December 2024
Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, College of Science, Southern University of Science and Technology Guangming Advanced Research Institute, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.
Organocatalytic chemo- and enantioselective reactions of 2-amino-3-subsituted indoles have been achieved for the first time. Via asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates, organocatalytic enantioselective dearomatization of 2-amino-3-subsituted indoles afforded an array of enantioenriched 3,3-disubstituted indolin-2-imines bearing a quaternary carbon stereocenter in 34-79% yields with 61-91% ee. With BocO as reaction partner, the organocatalytic enantioselective -acylation of 2-amino-3-subsituted indoles was established to furnish C-N axially chiral products in 22-98% yields with 73-92% ee.
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