Highly regio- and diastereoselective synthesis of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles, based on a post-Ugi condensation: joint experimental and computational study

Abstract

A novel series of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles were synthesized via a two-step pathway. In the first step, Ugi-four-component condensation of 2-formylindole, amines, (E)-4-alkoxy-4-oxobut-2-enoic acids, and isocyanides gave the corresponding Ugi-adducts. This adduct underwent intramolecular hydroamination in the presence of K2CO3 in CH3CN at room temperature to afford diastereoselective synthesis of a range of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles. A comparison of experimentally observed CD and UV–visible spectra with the theoretical DFT calculated ECD spectra was used to predict the major diastereomer.