An increasing demand in chiral compounds for the synthesis of optically active drugs and agrochemicals requires the development of new enantioselective transformations. Despite a tremendous progress in this field, it remains challenging to convert a racemic mixture directly into one of its enantiomers. Deracemizations fill this gap as they enable the direct conversion of a racemate into a single enantiomer without a change in structure and with excellent atom efficiency. Intrinsic limitations that have to be overcome are the loss of entropy as well as microscopic reversibility. In this regard, photochemistry can be an elegant approach to address these issues due to the compensation of entropy by light energy and the possibility of irreversible reaction pathways.<br/>The use of triplet sensitizers is a sophisticated way to realize such a catalytic photochemical deracemization. A compelling and at the same time challenging example is the deracemization of primary allene amides by using a chiral thioxanthone-based triplet sensitizer with a hydrogen bonding site. Despite the high flexibility of the substrates, only 2.5 mol% of catalyst were required to achieve an enantiomeric excess of up to 93% in excellent to quantitative yields for a variety of substrates bearing various functional groups.<br/>As most chiral compounds of interest exhibit point chirality, we turned our attention to the development of deracemization techniques at sp<sup>3</sup>-hybridized carbon centers. Highly encouraging preliminary results motivated us to develop a more generalized approach for photochemical deracemizations of relevant chiral building blocks for a vast number of bioactive molecules.

Overcoming the equilibrium state: Developement of novel photochemical deracemization reactions

ACS Spring 2022

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