Enantioselective Redox-Neutral Radical Addition of α-Imino Esters with Sulfonyl Hydrazides

The construction of chiral sp3–sp3 carbon–carbon bonds represents a central challenge in organic synthesis, critically enabling 3D molecular complexity for drug discovery. While transition metal-catalyzed asymmetric alkylation of unsaturated bonds offers a powerful route to these motifs, conventional strategies face inherent limitations: nucleophilic additions require preformed organometallic reagents via an external synthetic sequence, and recent flourishing reductive methods with alkyl halides demand stoichiometric terminal reductants. Herein, we disclose a cobalt-catalyzed, enantioselective redox-neutral radical addition that directly couples bench-stable unactivated alkyl sulfonyl hydrazides with various imines. This strategy eliminates external reductants while accommodating a broad substrate scope, delivering valuable α-amino esters in high yields and enantioselectivities. Crucially, the redox-neutral conditions enable the first asymmetric radical addition of N-TMS iminoesters, providing unprotected α,α-disubstituted amino acids directly without deprotection sequences. Mechanistic studies confirm alkyl radical intermediates in the stereoselective C–C bond formation. This method overcomes key limitations of existing approaches, offering a step-economical route to medicinally relevant chiral building blocks.