Enantioselective Synthesis of 2-Functionalized Tetrahydroquinolines through Biomimetic Reduction

Biomimetic asymmetric reduction of 2-functionalized quinolines has been successfully developed with the chiral and regenerable NAD(P)H model CYNAM in the presence of transfer catalyst simple achiral phosphoric acids, providing the chiral 2-functionalized tetrahydroquinolines with up to 99% ee. Using this methodology as a key step, a chiral and potent opioid analgesic containing a 1,2,3,4-tetrahydroquinoline motif was synthesized with high overall yield.

Automated summary

A biomimetic asymmetric reduction method for 2-functionalized quinolines using the chiral and regenerable NAD(P)H model CYNAM has been successfully developed, providing chiral 2-functionalized tetrahydroquinolines with up to 99% ee. By utilizing this method as a key step, a chiral and potent opioid analgesic containing a 1,2,3,4-tetrahydroquinoline motif was synthesized with high overall yield.