Aug 2026· Angewandte Chemie· Vol 65, pp.
e6267376
· 0 citations· 72 references
Medicine
Abstract
Semisaturated heterocycles are privileged scaffolds in natural products and pharmaceuticals, yet a general and versatile catalytic strategy to access these chiral architectures remains a formidable challenge. Herein, we report a unified synthetic platform utilizing the earth-abundant cobalt coupled with a chiral N,N'-dioxide ligand to unlock the tandem reactivity of vinyl carbenes for the enantioselective construction of diverse semisaturated heterocycles. We have achieved three distinct cascade transformations for modular and efficient access to 2,3-disubstituted dihydrobenzofurans, 1,2,3-trisubstituted indolines, and 2,3,4-trisubstituted benzomorpholines in excellent yields, exceptional enantioselectivities, and high diastereoselectivities, respectively. Mechanistic investigations, including kinetic studies and density functional theory (DFT) calculations, have elucidated that the cascade pathway involves vinylougous C(sp2)-H or N-H insertion of carbenoids, followed by an intramolecular conjugate addition cascade.The practical utility of this protocol is further highlighted by gram-scale syntheses and versatile product derivatizations, offering a powerful and practical tool for the synthesis of chiral heterocycles.
The P-chiral phosphine AntPhos was found to be the ligand of choice for nickel-catalyzed intramolecular reductive coupling reactions of 5-amino substituted 2,4-dienoates bearing a tethered aldehyde. This approach to heterocyclic compounds has little precedent in the literature; it provides, inter alia, ready access to...
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The development of general methods for the enantioselective synthesis of axially chiral molecules remains a longstanding challenge in organic synthesis. Among these, allenes represent a particularly important class of motifs due to their unique structural and electronic properties, yet their catalytic enantioselective...
Chiral amines are privileged scaffolds with pervasive importance across the organic synthesis. Nevertheless, the stereoselective construction of 1,3-diamines bearing multiple stereocenters represents a significant and persistent challenge in synthetic chemistry. Addressing this, we recognized aziridines as ideal yet un...
Helicenes are a class of structurally fascinating polycyclic aromatic molecules composed of ortho-fused aromatic rings, which adopt a screwed shape and exhibit helical chirality due to the steric repulsion between the two terminal rings. However, the catalytic enantioselective synthesis of helicenes, especially those...
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Heterohelicenes combine helical chirality with tunable electronic properties, making them attractive for applications in chiral materials and optoelectronics. However, their enantioselective synthesis, particularly for five-membered heterohelicenes, remains a long-standing challenge owing to the inherent synthetic di...
The normorphan framework is a compact, sp3-rich N-bridged scaffold found in biologically active natural products and increasingly valued as a three-dimensional platform for medicinal chemistry. Despite its synthetic and biological relevance, direct catalytic asymmetric access to functionalized normorphan-related archit...
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