Chemo‐, Diastereo‐, and Enantioselective Radical Cyclization of Enals to Access Cyclopentanols Bearing an α‐Quaternary Center

ABSTRACT Controlling both chemo‐ and stereoselectivity in reactions of sterically demanding radicals remains a fundamental challenge in the construction of vicinal stereocenters, particularly those bearing an α‐quaternary carbon center. Despite their synthetic value, asymmetric radical cyclization of bulky carbon‐centered radicals onto enals to access α‐quaternary cyclic alcohols remained undeveloped. Here we report a stereoconvergent asymmetric radical alkylation/cyclization cascade of enals with unactivated, sterically congested alkyl iodides, enabled by an earth‐abundant chromium catalyst supported by a chiral bisoxazoline ligand. This method provides direct access to cyclopentanol and 2,3‐dihydro‐1 H ‐inden‐1‐ol derivatives bearing an α‐quaternary stereocenter in good yields with excellent diastereo‐ and enantioselectivities (>20:1 d.r., up to 99% ee). The reaction proceeds under mild conditions, exhibits broad functional‐group tolerance, and completely suppresses the competing direct coupling of alkyl electrophiles with aldehydes. Experimental and DFT studies support a catalytic manifold in which a chiral Cr(II) complex mediates single‐electron generation of alkyl radicals for addition to enals and controls the enantiodetermining outer‐sphere cyclization of the resulting bulky tertiary radical onto the carbonyl group.