Sterically Engineered Mo─V Cluster Catalyst for Switchable <i>Z</i> / <i>E</i> ‐Selective Alkyne Hydrophosphorylation

ABSTRACT Stereodivergent alkyne hydrophosphorylation represents a formidable challenge in synthetic chemistry, particularly for selective and tunable synthesis of ( Z )‐ and ( E )‐alkenylphosphine oxides. Herein, we report a steric hindrance–mediated strategy that achieves switchable Z / E selectivity via rational design of a metal–organic‐functionalized phosphovanadomolybdate [PMo 8 V 4 O 40 (VO) 2 ][(VO)(IM) 4 ] 3 ·5.5H 2 O (IM = 1‐methylimidazole), which features a highly congested steric environment. Steric repulsion between the cluster framework and substrate enables highly Z ‐selective hydrophosphorylation, affording β ‐( Z )‐alkenylphosphine oxides in up to 81% yield with Z / E ratio of 21:1. Incorporation of AgOAc as a stereochemical modulator switches the pathway to afford β ‐( E )‐products in up to 80% yield with E / Z ratios up to 15:1. This heterogeneous catalytic system exhibits broad substrate tolerance, accommodating a diverse range of terminal alkynes with excellent chemo‐ and regioselectivity, including in the functionalization of complex pharmaceuticals, agrochemicals, and natural products, and gram‐scale reactions with pharmaceutical substrates were achieved in this catalytic system. These findings not only provide practical solutions for stereodivergent hydrophosphorylation but also offer fundamental insights into steric control in transition metal–catalyzed transformations.