Bicyclo[4.1.1]octanesvia Strain-Storage Cyclobutanone-AlkyneCoupling and Its Enantioselective Strain-Release Transformation toBicyclo[4.2.1]nonanes

Three-dimensional C(sp³)-rich bicyclic scaffolds are vital saturated bioisosteres and versatile building blocks in medicinal and synthetic chemistry. Notwithstanding the importance and progress, the synthesis of bicyclo[4.1.1] and bicyclo[4.2.1] scaffolds remains challenging. Herein, we unveil a rare nickel-catalyzed strain-storage cyclobutanone-alkyne coupling to prepare various functionalized bicyclo[4.1.1]octanes. Moreover, downstream strain-release transformation of bicyclo[4.1.1] scaffolds via rhodium-catalyzed enantioselective sequential C–C activation and 1,4-rhodium shift was efficiently achieved to fuse a variety of enantioenriched bicyclo[4.2.1] scaffolds with high chemo-, diastereo-, and enantioselectivity. Mechanistic studies revealed the well-tailored spironickelabicyclic intermediate with a rigid endo-cyclic olefin favors the strain-storage cyclometalation over the common strain-release-driven β-carbon elimination.