A Room-Temperature Rh-Catalyzed Kinetic Resolution Pathway for Expedient Access to P‑Stereogenic Cyclic Phosphinates

一种室温下铑催化的动力学拆分方法,可快速合成P-立体异构环状膦酸酯

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Abstract

P-Stereogenic center-embedded heterocycles are privileged scaffolds in pharmaceuticals and catalysis, yet their synthesis remains a formidable challenge, largely reliant on desymmetrization or asymmetric aromatic C-P cross-coupling. Herein, we report a room temperature Rh-catalyzed enantioselective ring-closing hydrofunctionalization of alkynylphosphinates that directly constructs kinetically favored, nonarene-fused P-stereogenic five-membered rings. DFT calculations revealed that the proximal ligation of the phenolic additive plays a critical role in accelerating P-H bond activation, thereby enabling efficient hydrofunctionalization across the alkynyl segment. This method accommodates diverse substituents located at the phosphorus atom and the alkynyl moiety, providing a versatile platform for accessing valuable building blocks for pharmaceutical and chiral ligand design.

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