A Photoenzyme for Challenging Lactam Radical Cyclizations.

Reductive radical cyclizations are ubiquitous in organic synthesis and have been applied to the synthesis of structurally complex molecules. -heterocyclic motifs can be prepared through the cyclization of -haloamides; however, slow rotation around the amide C-N bond results in preferential formation of an acyclic hydrodehalogenated product. Here, we compare four different methods for preparing , , , and -lactams via radical cyclization. We found that a photoenzymatic method using flavin-dependent 'ene'-reductases affords the highest level of product selectivity. We suggest that through selective binding of the amide isomer, the enzyme preorganizes the substrate for cyclization, helping to avoid premature radical termination.