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Catalytic Asymmetric Oxidative Coupling between C(sp)-H Bonds and Carboxylic Acids.

J Am Chem Soc

January 2025

State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Frontiers Science Center for New Organic Matter, Nankai University, Tianjin 300071, China.

The direct enantioselective functionalization of C(sp)-H bonds in organic molecules could fundamentally transform the synthesis of chiral molecules. In particular, the enantioselective oxidation of these bonds would dramatically change the production methods of chiral alcohols and esters, which are prevalent in natural products, pharmaceuticals, and fine chemicals. Remarkable advances have been made in the enantioselective construction of carbon-carbon and carbon-nitrogen bonds through the C(sp)-H bond functionalization.

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Two novel Pd-catalyzed protocols for the controllable synthesis of benzo[]furo[2,3-]azepines and furo[3,2-]indoles have been developed by intermolecular oxidative annulation of 2-(furan-2-yl)anilines and propargyl carbonates versus intramolecular C-H amination reactions. These two protocols feature great scalability, functional group tolerance, and relatively mild reaction conditions. Notably, the robust methodologies could also provide valuable opportunities for assembling azepine-fused benzothiophene, indole-fused benzothiophene, and indole-fused benzimidazole, which may have potential applications in the synthesis of related pharmaceuticals or polymeric materials.

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Rh(II)-Catalyzed Selective C(sp)-H/C(sp)-H Bonds Cascade Insertion to Construct [6-8-6] Benzo-Fused Scaffold.

Org Lett

December 2024

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.

The fused eight-membered carbocycles (EMCs) play vital roles in the medicinal and biological investigations of many natural products and marketed drugs. The traditional synthesis of [6-8-6] benzo-fused derivatives involves multistep reactions and low yields, making the development of a one-step synthesis method a more challenging work. Here, we present a novel strategy for one-step construction of [6-8-6] benzo-fused scaffold from propargyl diazoacetates substituted with benzyl-nitrogen heterocyclic ring via Rh(ll)-catalyzed carbene/alkyne metathesis (CAM) and selective C-H bond insertion.

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An efficient FLP-mediated cycloisomerization is described, providing easy access to quinolinium and chromenylium derivatives by treatment of readily available propargylanilines and aryl propargyl ethers with Lewis acidic boranes, respectively. The reaction proceeds via a 6--dig cyclization/dehydrogenation sequence. The heteroatom functions serve as Lewis bases in combination with Lewis acidic boranes to effect synergistic activation of an alkynyl triple bond and a C-H bond.

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This study provides a practical route to synthesize tetrasubstituted alkenes that involves Co(III)-catalyzed C-H bond activation and regioselective insertion of the alkyne, followed by chelation of the substrate hydroxyl to Co and migration of the pyridine group. Density functional theory studies revealed the origin of regioselectivity and elucidated the crucial role of the hydroxyl group for the migration of pyridine. The method can be conducted on a gram scale, is compatible with a wide range of substrates, and has a high functional group tolerance.

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