Reductive Photo-enzymatic Strategy for the Chemo-divergent Synthesis of Bromohydrin and Epoxides

CERUTTI SERRA LORENZO; GAMBOA GUILLERMO; OKSDATH-MANSILLA GABRIELA; BISOGNO ROMAN FABRICIO

GRAZ

Simposio; BIOTRANS 2021 Web-Conference; 2021

In Photobiocatalysis, the suitable orchestration of photo- and biocatalytic reactions has allowed access to new and more sustainable strategies in organic synthesis.[1]Most of the established photobiocatalytic strategies rely on photooxidation of a substrate and further biocatalytic transformation[2] and photorecycling of redox cofactors for well-established biocatalytic processes.[2] However, some asymmetric photoreductive reactions have been recently accomplished using enzymes.[3] With this in mind, here we present a sequential combined stereoselective bioreduction/selective photocatalytic one electron reduction in order to convert alpha,alpha-dibromoketones into valuable bromhydrins or epoxides with high optical purity.The ADH-catalised bioreduction of alpha,alpha-dibromoketones into the corresponding dibromhydrins was conducted with excellent conversion and enantiomeric excesses, as reported earlier.[4]The photoreduction step starting from the racemic dihalohydrin was optimised regarding photocatalyst, sacrificial electron donor, solvent composition, atmosphere and reaction time.From these experiments, two scenarios were recognized: on the one hand, selective monodebromination was observed when 2-PrOH was employed as solvent, thus affording the corresponding bromhydrin. On the other hand, monodebromination followed by spontaneous ring closure was evident in hydroalcoholic media giving rise to the corresponding epoxide.For the one pot sequential design, the bioreduction was in a sealed glass vial purged with Ar. Once the ketone has been consumed, photocatalyst, electron donor dissolved in a cosolvent is added under inert atmosphere. Then, the vial is irradiated with blue LED for 10-24 h with magnetic stirring. Full conversion and yields up to 80 % were obtained for the chiral bromhydrin and 65% for the styrene oxide.In this way, it is possible to direct the process to the formation of either the halohydrin or the epoxide by careful tuning of the reaction conditions. For the chemoselectivity, the sacrificial electron donor and solvent composition play a critical role.[1] M. G. López-Vidal, G. Gamboa, G. Oksdath-Mansilla, F. R. Bisogno. (2021). Photobiocatalysis. In Biocatalysis for Practitioners. Techniques, Reactions and Applications, Wiley-VCH (Ed.) Weinheim, Germany.[2] L. Schmermund, V. Jurkas,̌ F. F. Özgen, G. D. Barone, H. C. Büchsenschütz, C. K. Winkler, S. Schmidt, R. Kourist, W. Kroutil ACS Catal. 2019, 9, 4115-4144.[3] Y. Nakano, K. F. Biegasiewicz, T. K. Hyster, Curr. Op. Chem. Biol. 2019, 49,16-24.[4] K. Kędziora, F. R. Bisogno, I. Lavandera, V. Gotor-Fernández, J. Montejo-Bernardo, S. García-Granda, W. Kroutil, V. Gotor, ChemCatChem 2014, 6, 1066-1072.