The monoterpene citronellol often represents the substrate for the synthesis of other natural products and fragrances bearing α-branched tetrahydropyran moieties. In this contribution, we developed a process that combines in one-pot condition photocatalytic Schenck-ene reaction and biocatalytic halocyclization to synthesize enantiopure α-branched tetrahydropyrans starting from natural monoterpene citronellol. The reaction pathway of the enzymatic haloetherification, studied by combining experimental and theoretical studies, showed for the first time the key role played by the hydroperoxide functional group in the control of the regioselectivity of the cyclization step. Overall, a novel and sustainable synthetic procedure is reported as a new approach for α-branched tetrahydropyrans.

Vicinal halohydrins are key building blocks to produce bioactive molecules and drugs, especially if they can be obtained in enantiomerically pure form. In this study, we present a bi-enzymatic sequence that allows to obtain vic-halohydrins through a photochemoenzymatic olefin hydroxy halogenation followed by a lipase catalysed kinetic resolution. The absolute configuration of the resulting products was determined using Mosher's method.