Direct Asymmetric <i>α</i> ‐Alkylation of <i>β</i> ‐Ketocarbonyl Compounds with Simple Olefins by Photoredox‐Nickel‐Hydrogen Atom Transfer Triple Catalysis

Although the asymmetric α-alkylation of carbonyl compounds with activated olefins has already been established, extending this methodology to less activated or nonactivated olefins remains a significant challenge due to the polarity mismatch in these ionic processes. An alternative approach involves the activation of the parent carbonyl compounds into electrophilic α-carbonyl radicals, which could potentially overcome this limitation. However, the lack of efficient catalytic systems has impeded the wide adoption of this strategy, particularly in realm of the catalytic asymmetric reactions. Here, we present a cooperative triple catalytic system that integrates photoredox, chiral Lewis acid, and hydrogen atom transfer (HAT) catalysts to achieve a direct asymmetric α-alkylation of β-ketocarbonyl compounds using simple olefins as alkylating agents. By combining a multifunctional chiral nickel Lewis acid with an iridium photoredox catalyst and a thiophenol catalyst under visible light, we have developed a highly efficient process that is temporally synchronized to facilitate a novel mechanism of electron and hydrogen transfer. This triple catalytic approach enables the intermolecular coupling of β-ketocarbonyl compounds with both less and non-activated olefins. This redox-neutral protocol provides an atom- and step-economic route to enantioselectively synthesize high-value molecules featuring an all-carbon quaternary stereocenter from feedstock chemicals, while only consuming photons.