Combining Photo‐Organo Redox‐ and Enzyme Catalysis Facilitates Asymmetric C‐H Bond Functionalization

Abstract

In this study, we combined photo‐organo redox catalysis and biocatalysis to achieve asymmetric C–H bond functionalization of simple alkane starting materials. The photo‐organo catalyst anthraquinone sulfate (SAS) was employed to oxyfunctionalise alkanes to aldehydes and ketones. We coupled this light‐driven reaction with asymmetric enzymatic functionalisations to yield chiral hydroxynitriles, amines, acyloins and α‐chiral ketones with up to 99 % ee. In addition, we demonstrate functional group interconversion to alcohols, esters and carboxylic acids. The transformations can be performed as concurrent tandem reactions. We identified the degradation of substrates and inhibition of the biocatalysts as limiting factors affecting compatibility, due to reactive oxygen species generated in the photocatalytic step. These incompatibilities were addressed by reaction engineering, such as applying a two‐phase system or temporal and spatial separation of the catalysts. Using a selection of eleven starting alkanes, one photo‐organo catalyst and 8 diverse biocatalysts, we synthesized 26 products and report for the model compounds benzoin and mandelonitrile > 97 % ee at gram scale.

Retracted: Combined Photoredox/Enzymatic C−H Benzylic Hydroxylations

“…[14] In general, these two reaction manifolds are suitable candidates for combination because photocatalytic reactions typically occur at or neat ambient temperature and proceed through reactive intermediates that are stable towards water and function groups in proteins.O fp articular note,the Hartwig laboratory disclosed atandem cooperative photocatalytic/ene-reductase reaction to afford enantioenriched chiral building blocks. [16] Additionally,b oth photoredox and enzymatic catalysis have attracted great attention in the pharmaceutical industry for the synthesis of active pharmaceutical ingredients. [16] Additionally,b oth photoredox and enzymatic catalysis have attracted great attention in the pharmaceutical industry for the synthesis of active pharmaceutical ingredients.…”

Retracted: Combined Photoredox/Enzymatic C−H Benzylic Hydroxylations

“…[14c] TheH yster laboratory disclosed utilizing photocatalysis in combination with nicotinamide adenine dinucleotide phosphate (NAD(P)H) dependent ketoreductases (KREDs) [14a] and ene-reductases [14b,15] to facilitate non-native enzymatic reactivity.T he Hçhne and Schmidt laboratories demonstrated the combination of photocatalytic C À Hf unctionalization with benzaldehyde lyases, ene-reductases,k etoreductases and aminotransferases;h owever,t his chemistry was limited to low conversion and restricted substrate classes. [16] Additionally,b oth photoredox and enzymatic catalysis have attracted great attention in the pharmaceutical industry for the synthesis of active pharmaceutical ingredients. [17] Notwithstanding the potential of photocatalytic/enzymatic chemoenzymatic catalysis,t his merger provides new opportunities to develop selective and valuable chemical transformations.D espite the established capabilities of photochemical methods for CÀHo xidations and enzymatic carbonyl reductions,t he union of these two distinct chemistries has not yet been realized to its fullest potential.…”

Biocatalysis Fueled by Light: On the Versatile Combination of Photocatalysis and Enzymes

“…Ap hoto-biocatalytic cascade reactions equence addressed divergenta ccess to av ariety of different carbonyl andc arboxyl derivatives and amines starting from the same simple alkanes 78. [71] In the first step, sodium anthraquinone-2-sulfonate (81, SAS) served as av isible-light photocatalystf or the oxyfunctionalizationo f78,g iving rise to carbonyl compounds 79 (aldehydes or ketones). In am odulara pproach, these intermediates 79 were then subjected to downstream enzymatic reactions.…”