Electricity-Enhanced Lewis Acid-Catalyzed Asymmetric Radical Reactions

ConspectusAsymmetric catalytic radical reactions represent a powerful yet underexplored strategy for the efficient construction of chiral organic molecules. In this field, we have successfully integrated the advantages of electrosynthesis with chiral Lewis acid catalysis to establish an innovative outer-sphere catalytic mode based on chiral radical intermediates. The chiral Lewis acid catalyst activates carbonyl compounds to generate electron-rich enolate intermediates, thus lowering their oxidation potential while simultaneously generating key catalyst-associated radical intermediates under anodic oxidation. The Lewis acid-promoted electron transfer (LCET) mechanism inherently suppresses noncomplexed radical formation, resulting in minimal racemic background interference. Crucially, since the chiral catalyst is attached to the radical intermediate, the stereoselectivity can be modulated through rational ligand design, thereby achieving highly enantioselective radical transformations. This catalytic system is particularly noteworthy as the chiral catalyst engages in both the electron transfer process and stereoselective control. Based on this electrocatalytic platform, we have explored the reactivity of electrochemically generated chiral radical intermediates with various π-systems, including alkenes, alkynes, allenes, conjugated polyenes, and nitronate anions. These reactions consistently deliver excellent stereoselectivity to underscore the generality of this approach. This remarkable result has motivated us to further expand the scope of this strategy to develop asymmetric oxidative and dehydrogenative coupling reactions. Specifically, employing a nickel-bound α-carbonyl radical as a chiral template, we achieved reactions with diverse transient active intermediates, such as radicals and radical cation intermediates generated <i>in situ</i> under electrochemical conditions. Moreover, a new dual-catalytic electrochemical asymmetric system was developed to enable stereodivergent anodically oxidative homocoupling reactions for the predictable synthesis of all stereoisomers of the target molecule with precise control over both absolute and relative stereochemical configurations. The success of this electrocatalytic system demonstrates the synthetic potential of chiral radical intermediates while simultaneously opening new avenues for their application in the asymmetric and stereodivergent synthesis of complex molecular architectures. These advances establish a robust foundation for the advancement of enantioselective electrochemistry and highlight the considerable potential for broader application in synthetic methodologies.