Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways*

Abstract

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the (S)- or the (R)-enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CN-OA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99 % ee). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93 % ee).

Keywords: C−H activation; carbon nitrides; chromoselectivity; photobiocatalysis; unspecific peroxygenases.

Scheme 1

A) General approaches to control of the outcome of a chemical reaction. B) Chromoselective control in photocatalytic C−H‐arylations. ^[5a] C) This study: Chromoselective control of the stereochemical outcome of photo‐chemo‐enzymatic reactions.

Figure 1

Chromoselective generation of excited CN‐OA‐m species with different oxidation potentials. A) Switching between π–π* and n–π* electron transitions using different wavelengths. B) The oxidation of ethylbenzene 1 a to acetophenone 3 a is only possible using blue light.

Figure 2

Influence of different wavelengths and buffers on the photo‐chemo‐enzymatic hydroxylation of ethylbenzene; reaction conditions: AaeUPO (25 nM), ethylbenzene (10 mM), CN‐OA‐m (2 mg mL⁻¹), MeOH (250 mM), KPi (100 mM, pH 7.5) or tricine (100 mM, pH 7.5), 455 nm (1440 μmol photons m⁻² s⁻¹) or 528 nm (1330 μmol photons m⁻² s⁻¹), 30 °C, 8 h.

Scheme 2

Substrate scope of AaeUPO using H₂O₂ generated by CN‐OA‐m under green light irradiation. Absolute configurations were determined by reference material except otherwise stated. [a] Based on external calibration curves of 2 i. [b] (R)‐Enantiomer determined by measurement of the specific rotation (20 °C, c=1.00, CHCl₃) and comparison to literature.

Scheme 3

Light‐driven enantioselective oxyfunctionalizations of 1 a by using chromoselective CN‐OA‐m and AaeUPO or ADH‐A.