Enantioselective Photocatalysis Using a Privileged Al-Salen Complex

ConspectusEnantioselective catalysts that exhibit broad generality are disruptive innovators in contemporary synthesis and are considered to be "privileged" on account of their expansive reactivity/selectivity profiles. Operating in the ground state, these species simultaneously regulate reactivity and orchestrate the translation of chiral information with exquisite efficiency: achieving parity in higher-energy (excited-state) scenarios remains a frontier in contemporary catalysis. Advancing this field will require new structure-activation guidelines to be delineated that reflect the energetic realities of achieving chiral induction in non-ground-state environments, thereby expediting the discovery of privileged photocatalysts. Earth-abundant aluminum-salen (Al-salen) complexes, which have a venerable history in ground-state enantioselective catalysis, show great promise in reconciling this disparity on account of their well-defined photophysical properties. In this Account, the potential of these catalysts in engaging various substrates via discrete activation modes to furnish optically enriched products with high levels of reliability is discussed. The deployment of commercial Al-salen complexes in the single electron transfer (SET)-enabled deracemization of cyclopropyl ketones is an exemplar. Irradiation of a commercial Al-salen complex augments the function of the catalyst to enable efficient deracemization (up to 98:2 e.r.), thereby eliminating the need for directing units. In stark contrast to conventional deracemization approaches that are predicated on C(sp³)-H deprotonation/reprotonation sequences, the transformation is characterized by a key C(sp³)-C(sp³) bond cleavage/cyclization process. Subsequent downstream manipulations of the enantioenriched products demonstrate the synthetic utility of the methodology. To illustrate mechanistic diversity using the same Al-salen complex, an enantioselective photocyclization under the auspices of energy transfer (EnT) catalysis is described. The photocyclization of acrylanilides under operationally simple conditions facilitates access to a diverse group of heterocyclic products (up to quantitative yield and 96:4 e.r.) using an Al-salen as the sole chiral operator. Collectively, these mechanistically distinct scenarios illustrate that light activation is a powerful strategy to augment the reactivity arsenal of a ubiquitous small molecule catalyst that is considered to be privileged in the ground state. The mechanistic foundations of reaction development are surveyed (combined experimental and computational approach), together with a perspective on the impact of this enabling technology in chiral functional molecule discovery. This Account serves to emphasize the synthetic utility of leveraging photochemical activation to mitigate intrinsic constraints of processes that might be considered to be thermochemically challenging.