L-Proline catalyzed multi-component synthesis of N-pyridyl-tetrahydroisoquinolines and their α-C(sp³)-H oxygenation

Herein, we report an effective multi-component synthesis that starts with readily available starting materials and accesses poly-substituted pyridine derivatives by using L-proline as a benign catalyst. This process uses cyclic amines, aldehydes, and malononitrile in a condensation reaction to produce a variety of pyridine derivatives under mild conditions. Furthermore, depending on the catalysts used, the selective synthesis of an amide and/or an aldehyde functionality is achieved through α-C(sp³)-H oxygenation of the tertiary amine moiety in the resultant pyridine derivatives. The pyridine ring's nitrogen atom plays a crucial role in accelerating C-H oxygenation at the α-position of the tertiary amine, highlighting the synthetic versatility and usefulness of this method.