Chiral 1,3,2-Oxazaborolidine Catalysts for Enantioselective Photochemical Reactions.

Abstract

ConspectusAsymmetric synthesis has posed a significant challenge to organic chemists for over a century. Several strategies have been developed to synthesize enantiomerically enriched compounds, which are ubiquitous in the pharmaceutical and agrochemical industries. While many organometallic and organic catalysts have been found to mediate thermal enantioselective reactions, the field of photochemistry lacks similar depth. Recently, chiral 1,3,2-oxazaborolidines have made the transition from Lewis acids that were exclusively applied to thermal reactions to catalysts for enantioselective photochemical reactions. Due to their modular structure, various 1,3,2-oxazaborolidines are readily available and can be easily fitted to a given chemical transformation. Their use holds great promise for future developments in photochemistry. This Account gives an overview of the substrate classes that are known to undergo enantioselective photochemical transformations in the presence of chiral 1,3,2-oxazaborolidines and touches on the catalytic mode of action, on the proposed enantiodifferentiation mechanism, as well as on recent computational studies.Based on the discovery that the presence of Lewis acids enhances the efficiency of coumarin [2 + 2] photocycloadditions, chiral 1,3,2-oxazaborolidines were applied in 2010 for the first time to prepare enantiomerically enriched photoproducts. These Lewis acids were then successfully used in intramolecular [2 + 2] photocycloaddition reactions of 1-alkenoyl-5,6-dihydro-4-pyridones and 3-alkenyloxy-2-cycloalkenones. In the course of this work, it became evident that the chiral 1,3,2-oxazaborolidine must be tailored to the specific reaction; it was shown that both inter- and intramolecular [2 + 2] photocycloadditions of cyclic enones can be conducted enantioselectively, but the aryl rings of the chiral Lewis acids require different substitution patterns. In all [2 + 2] photocycloaddition reactions in which chiral 1,3,2-oxazaborolidines were used as catalysts, the catalyst loading could not be decreased below 50 mol % without sacrificing enantioselectivity due to competitive racemic background reactions. To overcome this constraint, substrates that reacted exclusively when bound to an oxazaborolidine were tested, notably phenanthrene-9-carboxaldehydes and cyclohexa-2,4-dienones. The former substrate class underwent an ortho photocycloaddition, the latter an oxadi-π-methane rearrangement. Several new 1,3,2-oxazaborolidines were designed, and the products were obtained in high enantioselectivity with only 10 mol % of catalyst. Recently, an iridium-based triplet sensitizer was employed to facilitate enantioselective [2 + 2] photocycloadditions of cinnamates with 25 mol % of chiral 1,3,2-oxazaborolidine. In this case, the relatively low catalyst loading was possible because the oxazaborolidine–substrate complex exhibits a lower triplet energy and an improved electronic coupling compared to the uncomplexed substrate, allowing for a selective energy transfer.By synthetic and theoretical studies, it has become evident that chiral 1,3,2-oxazaborolidines are multifaceted catalysts: they change absorption behavior, alter energetic states, and induce chirality. While a diverse set of substrates has been shown to undergo enantioselective photochemical transformations in the presence of chiral 1,3,2-oxazaborolidines either through direct excitation or through triplet sensitization, these catalysts took on different roles for different substrates. Based on the studies presented in this Account, it can be assumed that there are still more photochemical reactions and substrate classes that could profit from chiral 1,3,2-oxazaborolidines.