Functional group transfer (FGT) strategies offer efficient and selective routes to molecular complexity. However, strain-release-driven variants beyond norbornadiene scaffolds remain scant. Herein, we disclose the −OH transfer from diphenyl phosphine oxide (DPPO) to bicyclo1.1.0butane (BCB), exploiting its high ring strain in a regio and diastereoselective manner. Specifically, we developed Cu(OTf)2 catalysis that delivers products with high diastereoselectivity, while the In(OTf)3/HFIP-system enables diastereodivergent control. Catalytic DPPO usage renders the strategy stereoselective and atom-economic. We also document a Lewis-acid-catalyzed Pudovik reaction (P−H insertion) of DPPO via the strain release of BCB, where a switch to Ni(OTf)2 triggers the Pudovik reaction, furnishing phosphinylated cyclobutanes. Mechanistic studies and DFT calculations support a strain-release-driven P-H insertion as the initial step in this −OH transfer reaction. The resulting hydroxylated and phosphine-oxide-containing cyclobutanes combine a rigid 3D architecture with tunable physicochemical properties, offering value in drug discovery and ligand design.
Das et al. (Wed,) studied this question.