Imine Reductase Cascades for the Synthesis of Saturated N-Heterocycles

Saturated N-heterocycles constitute a vital scaffold for pharmaceutical chemistry, but are challenging to access synthetically, particularly in asymmetric mode. Here we demonstrate how imine reductases can achieve annulation through tandem inter and intramolecular reductive amination processes. Imine reductases were used in combination with further enzymes to access un-substituted, α-substituted and α,α’-disubstituted N-heterocycles from simple starting materials, in one pot and under benign conditions. The work was exemplified in regard to product scope and a new route to the valuable natural product nicotine was demonstrated.