Application of modified Pictet-Spengler reaction for the synthesis of thiazolo- and pyrazolo-quinolines

Two new thiazole and pyrazole-based arylamine substrate have been used for the Pictet-Spengler reaction. This is in contrast to the traditionally used indole/imidazole-based aliphatic amine substrates that has remained in use for the last ∼100 years. The condensation of both the substrates with a variety of aldehydes in the presence of 2% TFA-DCM at 0° for 30 min or pTsOH in toluene at reflux led to the synthesis of thiazoloquinolines and pyrazoloquinolines, respectively. Unlike aliphatic amine substrates, our substrates readily underwent Pictet-Spengler cyclization even with aldehydes having electron donating group. The studies are based on a new concept proposed by us that arylamines linked to an activated heterocyclic ring can lead to a variety of second-generation substrates for the Pictet-Spengler cyclization. Our studies open up new avenues for the application of Pictet-Spengler reaction beyond syntheses of the tetrahydroisoquinolines and tetrahydro-β-carbolines.