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

Abstract

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.