Beyond conventional Brønsted acid catalysis: leveraging the impact of charged moiety on the phenol for the construction of julolidine units

Abstract

In organocatalysis, the choice of chemical functionality and its mode of interaction with the substrate is vital. This necessitates proper design, ideal reaction parameters and harmony between the solvents, reagents and catalysts. In this context, enhancement of the catalytic active site via electrostatic effects has been receiving attention recently and we strongly believe this methodology will have a great impact in the field of organocatalysis. Here we report the catalytic activity of electrostatically tuned phenols for the construction of fused heterocyclic compound like julolidine in high yields and selectivities. The charged substituents on the phenolic moiety amplify the catalytic activity by enhancing the rate of the reaction, by orders of magnitude. We performed control experiments, kinetic studies, FT-IR and NMR investigations to probe the mechanistic underpinnings to the formation of the julolidine unit. These studies revealed the remote effects of ETP-6 and its catalytic behavior. We also identified and isolated the reaction intermediate, and proposed the stepwise sequences involved in the construction of the julolildine ring.