Asymmetric Catalytic Radical Reactions Enabled by Chiral <i>N</i>,<i>N</i>′-Dioxide–Metal Complexes

ConspectusThe strategic implementation of asymmetric catalytic radical reactions has evolved into a sophisticated methodology for constructing stereogenic centers, driven by remarkable advancements in radical generation techniques. However, achieving high stereoselectivity remains a formidable challenge due to the inherent high reactivity, transient lifetime of radical species, and presence of competing racemic background pathways. Addressing these limitations necessitates precise catalytic systems capable of orchestrating radical generation and enantioselective transformation in a controlled manner. In this Account, we systematically present our recent progress in enantioselective radical transformations mediated by chiral <i>N</i>,<i>N</i>'-dioxide-metal complexes, which have previously been widely used in polar reactions. Our mechanistic investigations categorize these transformations into three distinct paradigms based on radical generation strategies. (1) Oxidant-driven radical generation: Leveraging oxidants─hypervalent iodine reagents, peroxides, or molecular oxygen─we achieved alkyl radical formation. By synergizing these oxidants with redox-active or redox-inert chiral <i>N,N</i>'-dioxide-metal catalysts, we accomplished asymmetric difunctionalization of both electron-deficient and electron-rich olefins, alongside enantioselective radical cross-coupling reactions. (2) Merging photocatalytic strategy: Visible light irradiation facilitates the activation of metallic or organic photocatalysts (PCs), generating excited state species for redox or hydrogen atom transfer (HAT) processes. This enables the selective cleavage of inert C(sp³)-H bonds in hydrocarbons or C(sp²)-H bonds in aldehydes, producing diverse radical intermediates. Integration with chiral Lewis acid catalysts allows enantioselective radical additions to ketones, imines, and α,β-unsaturated carbonyl compounds, establishing C-C bonds under mild conditions without use of preactivated radical generators. Furthermore, energy-transfer photocatalysis combined with chiral Lewis acids promotes cyclization via C═C bond activation. Besides, an electron-shuttle strategy has been developed to balance radical generation from photoactive substrates, enabling asymmetric acylation and alkylation of aldimines. (3) Lewis acid-enabled substrate photoexcitation: We disclosed photocatalyst-free approaches wherein chiral <i>N</i>,<i>N</i>'-dioxide-metal complexes modulate substrate photophysics. Chiral Lewis acid coordination with several carbonyls or imines alters their photochemical properties. Interestingly, this activation of some C═X unsaturated compounds under light enhances their reduction potentials for single electron transfer (SET) as a temporary oxidant, enabling direct radical alkylation of ketones/imines. Alternatively, the strategy can stabilize triplet excited states.Collectively, our studies elucidate mechanistic frameworks for stereocontrol in radical reactions, demonstrating the versatility of chiral Lewis acid catalysts in merging photocatalysis, radical chemistry, and C-H functionalization. The developed methodologies offer practical synthetic routes while addressing fundamental challenges in selectivity and efficiency. We envision that this Account will inspire further exploration of asymmetric radical systems, fostering advancements in catalytic diversity and mechanistic understanding.