A Solvent-free, Catalyst-free Formal [3+3] Cycloaddition Dearomatization Strategy: Towards New Fluorophores for Biomolecules Labelling

Abstract

A general, sustainable dearomatization reaction for nitrogen-containing heterocycles was developed. Under solvent free conditions and without catalyst, the biorenewable methyl coumalate (MC) reacted as an efficient C₃ partner to convert nine types of basic aromatic rings into their pyrido[1,2-a] fused derivatives in good to excellent yields. The fluorescence properties of some of the products were harnessed to conjugate fluorescent tags to bovine serum albumin (BSA) and immunoglobulin G.

Keywords: Michael addition; dearomatization; fluorescent probe; methyl coumalate; nitrogen heterocycles.