New strategies in asymmetric catalysis have been a primary target in synthetic organic chemistry due to its widespread application in the production of pharmaceuticals, chiral materials, agrochemicals, and fine chemicals. As a readily available, renewable, and powerful tool in organic synthesis, photocatalysis — in particular, visible light-mediated catalysis — has played an important role in asymmetric synthesis through single electron transfer or triplet energy transfer. Despite a large variety of achievements, the development of asymmetric photocatalytic methods remains a significant challenge stemming from the high intrinsic reactivity of radical species and the high rate of undesired background reactions. To overcome these difficulties, one key strategy to control enantioselectivity in photocatalytic reactions is the development of cooperative catalysis that combines photocatalysis with well-established transition metal catalysis or organocatalysis. As early as 2005, Bach reported an enantioselective photoredox-mediated cyclization of aminoethyl quinolone with the use of a chiral bifunctional catalyst with a chiral hydrogen-bonding unit and an achiral photocatalytic unit. In 2008, MacMillan designed a photocatalytic system that merged photocatalysis and organocatalysis to realize a direct asymmetric alkylation of aldehydes under visible light. Inspired by these pioneering works, current asymmetric photocatalysis has mainly relied on two strategies: (1) dual catalysis involving two catalysts consisting of an achiral photocatalyst and an independent chiral cocatalyst; (2) single bifunctional catalyst integrating excitation and stereoselective control. Along these lines, trifunctional catalytic systems (TCA) by the merger of photocatalysis, organocatalysis with transition-metal catalysis provide the opportunity to reap the benefits of all catalytic manifolds. However, the concept has been only adopted in a racemic manner and less explored in asymmetric catalysis. The design and invention of trifunctional catalytic systems (TCA) is challenging but highly desirable to pursue novel disconnections and unprecedented reactivity.
To address this challenging task, the researcher will design trifunctional catalytic systems (TCA) comprising bifunctional photocatalysts and transition-metal catalysts. In this system, a bifunctional chiral catalyst, incorporating a hydrogen-bonding aryl ketone motif, will activate amides to generate α-amido radicals through photoinduced hydrogen atom transfer (HAT). This catalyst will simultaneously control the radical reactivity in an enantioselective manner. The transition-metal component will provide an additional mode of substrate activation and facilitate completion of the photocatalytic cycle. The specific objectives of this project are as follows: Catalyst Design: Develop novel bifunctional chiral photocatalysts based on hydrogen-bonding aryl ketone frameworks to enable amide activation via photoinduced HAT and to induce stereocontrol. Reaction Development: Combine these photocatalysts with transition-metal catalysts (Co, Cu, Ni) to construct TCA systems that enable N–α C–H alkenylation, arylation, alkoxylation, and trifluoromethylation reactions with high enantioselectivity. Mechanistic Studies: Elucidate the electronic, radical, and stereochemical mechanisms governing TCA reactions, thereby providing a theoretical foundation for the rational design of next-generation asymmetric catalytic systems.
