Ring contraction reactions facilitate easy access to carbo- and heterocyclic scaffolds from readily available precursors and have therefore enjoyed great popularity as a strategy in organic synthesis for a long time. By repurposing commercial alcohol dehydrogenases as borrowing hydrogen biocatalysts, we were able to develop a rare example of an enzymatic ring contraction methodology, where racemic 2-hydroxypyranones can be converted in an enantioconvergent manner to the corresponding 5-membered butenolides. The overall transformation is redox self-sufficient without the need for cofactor recycling systems and delivers gamma-lactones in excellent optical purities. To underline the synthetic value of this ring contraction, the methodology was successfully applied in the preparation of an Osmunda butenolide and in the formal total synthesis of threo-cavernosine. Moreover, the biocatalytic tool was incorporated into a multi-step cascade consisting of six enzymes, achieving the formal enantioselective dearomatization of a furfuryl alcohol to deliver the corresponding saturated gamma-lactone in >99% ee.
