TY - JOUR
T1 - Combining Photo-Organo Redox- and Enzyme Catalysis Facilitates Asymmetric C-H Bond Functionalization
AU - Zhang, Wuyuan
AU - Fernández-Fueyo, Elena
AU - Hollmann, Frank
AU - Leemans Martin, Laura
AU - Pesic, Milja
AU - Wardenga, Rainer
AU - Höhne, Matthias
AU - Schmidt, S
N1 - doi: 10.1002/ejoc.201801692
PY - 2019/1/10
Y1 - 2019/1/10
N2 - 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.
AB - 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.
KW - Photocatalysis
KW - Chemoenzymatic cascades
KW - Photo-organo catalyst
KW - Asymmetric synthesis
KW - Enzymes
U2 - 10.1002/ejoc.201801692
DO - 10.1002/ejoc.201801692
M3 - Article
C2 - 31007570
SN - 1434-193X
VL - 2019
SP - 80
EP - 84
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
IS - 1
ER -