Access to Uncharted (Ethoxy)difluoromethylated‐Containing Tetrahydrofurans by Hydrogenation

Fluorinated (hetero)cyclic compounds have garnered attention over the years, offering key building blocks in medicinally relevant molecules. However, the synthesis of fluorinated tetrahydrofurans remains a synthetic challenge to reach. Herein, we developed an efficient and robust approach for the synthesis of cis ‐(ethoxycarbonyl)difluoromethylated tetrahydrofurans. Using the inexpensive Pd/C catalyst, the diastereoselective hydrogenation of functionalized CF 2 CO 2 Et‐containing furans was achieved under mild reaction conditions. Access to unprecedented cis ‐fluorinated tetrahydrofurans with isolated yields of up to 74% and diastereomeric ratios up to 95:5 (12 examples) was reached. Pleasingly, under slightly modified reaction conditions, 5‐arylated CF 2 CO 2 Et‐containing furans were smoothly converted into the valuable α,α‐difluoro‐β‐hydroxyesters (five examples, up to 66% yield). Overall, the protocol exhibited good functional‐group tolerance and was easily scaled up. The synthetic utility of the CF 2 CO 2 Et moiety was further illustrated by its conversion into various other fluorinated groups.