Vinylcyclopropanes as Three-Carbon Synthons in Rhodium-Catalyzed Cycloadditions: Reaction Development, Mechanistic Studies, New Inspirations, and Synthetic Applications

作者：Pan Zhang, Zhi‐Xiang Yu · 发表于：Accounts of Chemical Research · 年份：2025 · DOI：10.1021/acs.accounts.4c00779 · 被引用次数：23 · 研究领域：Cyclopropane Reaction Mechanisms、Catalytic Alkyne Reactions、Catalytic C–H Functionalization Methods

Conspectus Cyclic structures are common in natural products and pharmaceuticals, but pose major synthetic challenges. Transition metal–catalyzed cycloadditions provide a direct and efficient route to complex ring systems in a single step. The demand for new transition metal–catalyzed cycloadditions remains high, as these methods enable access to diverse ring systems with unique substituents and stereochemistries that are often unattainable through existing cycloaddition techniques. Vinylcyclopropanes (VCPs) are widely recognized as versatile five-carbon (C 5 ) synthons in various transition metal-catalyzed cycloadditions, including [5 + 1], [5 + 2], and [5 + 2 + 1] reactions. In these reactions, VCP uses its vinyl group to facilitate C–C bond cleavage in the strained cyclopropane, aided by transition metals. In contrast, isolated cyclopropanes typically lack this reactivity. Building on these advantages, we discovered that by altering the connectivity between VCPs and other synthons, such as alkenes, alkynes, allenes, or dienes, VCPs can act as novel three-carbon (C 3 ) synthons, enabling previously unknown cycloadditions. This account outlines these discoveries. By connecting two-carbon (C 2 ) synthons to VCPs at positions 1, 2, or α, we created various substrates, including 2- trans -ene/allene-VCPs, 1-ene/yne/allene-VCPs, and α-ene-VCPs. These substrates undergo [3 + 2] cycloadditions to construct fused bicyclic structures. Notably, 1-ene/yne/allene-VCPs enable the constru...