Synthesis of β-Quaternary Lactams Using Photoenzymatic Catalysis

Quaternary carbons are useful motifs in chemical synthesis but can be challenging to prepare using many chemical methods. Here, we report a stereoselective synthesis of β-quaternary lactams using flavin-dependent ‘ene’-reductases via a 5-exo-trig radical cyclization. The products are formed in moderate to good levels of enantioselectivity using an ‘ene’-reductase variant from Zymomonas mobilis. This method highlights the opportunity for biocatalysis to form quaternary centers using non-natural reactions.