From Diazonium Salts to Optically Active 1‐Arylpropan‐2‐ols Through a Sequential Photobiocatalytic Approach

Abstract

The photocatalytic Meerwein arylation between aromatic diazonium salts and isopropenyl acetate under blue LED light irradiation in aqueous medium has been deeply investigated. Optimization of the reaction conditions in terms of substrate concentration, ester equivalents, cosolvent type and amount, reaction time and photocatalyst source, has allowed the access to a variety of 1‐arylpropan‐2‐ones with yields up to 95% using 9‐mesityl‐10‐methylacridinium perchlorate ([Acr‐Mes]ClO4). Next, the design of a one‐pot sequential photobiocatalytic linear approach was accomplished, by the combination of the Meerwein arylation with the bioreduction of the corresponding ketone intermediates. Thus, a total of 19 pairs of 1‐arylpropan‐2‐ol enantiomers were obtained depending on the alcohol dehydrogenase stereopreference. Global yields up to 76% were attained with high to excellent stereoselectivity (90 to >99% ee). Also, it was possible to get access to both 1‐phenylpropan‐2‐ol antipodes (51–53% yield) starting from aniline through a one‐pot three‐step sequential photobiocatalytic protocol.

One-pot chemo- and photo-enzymatic linear cascade processes

“…In a different approach to obtain optically active 1-arylpropan-2-ols, the authors combined the photocatalytic Meerwein arylation between aromatic diazonium salts and isopropenyl acetate under blue LED light irradiation with the bioreduction of the corresponding ketone intermediates. 433 The first step was performed in aqueous medium using ([Acr-Mes]ClO 4 ) as a photocatalyst, and the resulting ketone was reduced to the corresponding chiral alcohol in a sequential step using an alcohol dehydrogenase. Using ADHs of opposite stereopreference a total of 19 pairs of 1-arylpropan-2-ol enantiomers were obtained with global yields of up to 76% and high to excellent stereoselectivity (90 to >99% ee) (Scheme 133).…”