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

Abstract

Conspectus Asymmetric 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 sele...

Construction of Chiral Cyclic Compounds Enabled by Enantioselective Photocatalysis

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“…This review mainly discusses the research progress of enantioselective photocatalysis for constructing chiral cyclic compounds by photo-induced asymmetric cycloaddition reaction in the past 5 years, though some comprehensive contents regarding this topic were reported by the pioneers [4][5][6][7][8]. This paper is divided into seven parts according to the structural types of rings: the construction of 3-membered rings, 4-membered rings, 5-membered rings, 6-membered rings, 7-membered rings, macroring, and multi-rings.…”

The Merger of Photocatalyzed Hydrogen Atom Transfer with Transition Metal Catalysis for C−H Functionalization of Alkanes and Cycloalkanes

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“…[58][59][60][61][62] However, development of such processes remains a formidable challenge as a result of the incompatibility of different catalytic cycles and the difficulty of controlling the stereochemistry of transformations of high-energy intermediates, particularly radicals and radical ions. [63][64][65][66][67] In 2020, our group developed a photocatalyzed threecomponent asymmetric sulfonation reaction between a cycloalkane (or other C(sp 3 )À H precursors such as toluene derivatives or ethers), a SO 2 surrogate and an α,β-unsaturated carbonyl compound (Scheme 6). [68] The dual catalyst system consists of a HAT photocatalyst, 5,7,12,14-pentacenetetrone (PT) and a chiral nickel catalyst with a bisoxazoline ligand (L1) and showcases a high level of regio-and enantioselectivity in the reaction (> 45 examples, up to > 50 : 1 rr and 95 % ee).…”

Visible‐Light‐Induced Intramolecular Double Dearomative Cycloaddition of Arenes

“…[5] In this regard, pioneering works from the groups of Glorius, [6] Bach, [7] and Meggers [8] unlocked the reactivity of excited-state aromatic compounds for dearoma-tive [2+2] cycloaddition reactions. [9] Our group [10] and others [11] further demonstrated the straightforward assembly of highly strained polycyclic indoline derivatives and analogues via this strategy. Thanks to the distinctive reactivities of diradical intermediates on excited-states, the visible-lightinduced dearomative cycloaddition reactions provide indispensable methods for the target molecules that are not easily accessible using ground-state transformations.…”