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

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

Simposio; BioTrans 2021; 2021

In Photobiocatalysis, the suitable orchestration of photo- and biocatalytic reactions has allowedaccess to new and more sustainable strategies in organic synthesis.[1]Most of the established photobiocatalytic strategies rely on photooxidation of a substrate andfurther biocatalytic transformation[2] and photorecycling of redox cofactors for well-establishedbiocatalytic processes.[2] However, some asymmetric photoreductive reactions have beenrecently accomplished using enzymes.[3] With this in mind, here we present a sequentialcombined stereoselective bioreduction/selective photocatalytic one electron reduction in orderto convert ,-dibromoketones into valuable bromhydrins or epoxides with high optical purity.Figure 1. Chemodivergent synthesis of bromhydrins and epoxides by means of photobiocatalytic process.The ADH-catalised bioreduction of ,-dibromoketones into the corresponding dibromhydrinswas conducted with excellent conversion and enantiomeric excesses, as reported earlier.[4]The photoreduction step starting from the racemic dihalohydrin was optimised regardingphotocatalyst, sacrificial electron donor, solvent composition, atmosphere and reaction time.From these experiments, two scenarios were recognized: on the one hand, selectivemonodebromination was observed when 2-PrOH was employed as solvent, thus affording thecorresponding bromhydrin. On the other hand, monodebromination followed by spontaneousring 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 isadded under inert atmosphere. Then, the vial is irradiated with blue LED for 10-24 h withmagnetic stirring. Full conversion and yields up to 80 % were obtained for the chiral bromhydrinand 65% for the styrene oxide.In this way, it is possible to direct the process to the formation of either the halohydrin or theepoxide by careful tuning of the reaction conditions. For the chemoselectivity, the sacrificialelectron donor and solvent composition play a critical role.References[1] M. G. López-Vidal, G. Gamboa, G. Oksdath-Mansilla, F. R. Bisogno. (2021). Photobiocatalysis. InBiocatalysis 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.