Synthesis of tetrahydrofuro[3,2- c]pyridines via Pictet-Spengler reaction

Abstract

A semi-one-pot method for the synthesis of 4-substituted tetrahydrofuro[3,2-c]pyridines by the Pictet-Spengler reaction was developed. The method is based on the condensation of easily accessibly 2-(5-methylfuran-2-yl)ethanamine with commercially available aromatic aldehydes followed by acid-catalyzed Pictet-Spengler cyclization. Using this approach, we synthesized a range of 4-substituted tetrahydrofuro[3,2-c]pyridines in reasonable yields. The reactivity of some of the products was investigated and selected synthetic transformations of the obtained tetrahydrofuro[3,2-c]pyridines were shown.

Keywords: 1,4-diketone; Paal–Knorr reaction; Pictet–Spengler reaction; acid hydrolysis; tetrahydrofuro[3,2-c]pyridines.