Stereoselective Access to <i>γ</i> , <i>γ</i> ‐Dihalo‐ <i>β</i> ‐Enols From Alkynes Combining Visible Light and Biocatalysis

Merging different strategies in one‐pot processes is attracting considerable attention due to their straightforward and sustainable potential for synthesizing novel organic compounds. In particular, the exquisite selectivity displayed by enzymes and the possibility of coupling biotransformations with metal‐, photo and electrocatalytic processes open new avenues for stereoselective synthesis. Herein, the preparation of chiral (hetero)aryl‐3,3‐dihalopro‐2‐en‐1‐ols is described for the first time. To achieve this, a photochemical and biocatalytic one‐pot sequence is developed, employing visible light irradiation and stereoselective alcohol dehydrogenases (ADHs) for the transformation of commercially available alkynes into optically active compounds in an aqueous medium. The one‐pot, two‐step sequential approach involves a photocatalyst‐free reaction between terminal and internal alkynes with polyhalomethanes, leading to gem ‐dihaloenones, which are subsequently reduced using ADHs. After optimizing the individual steps and identifying suitable conditions for combining both processes, the use of complementary ADHs enables the synthesis of a novel family of optically active allylic alcohols with high stereoselectivity. Their chemical derivatization is further explored, allowing the stereoselective synthesis of a chiral propargylic alcohol from the corresponding γ , γ ‐dihalo‐ β ‐enol.