Direct Introduction of −OCD₃ into the Hantzsch Pyrrole Synthesis via Multicomponent Cascade Cyclization: Synthesis of Fully Substituted Pyrrole Derivatives

Abstract

A I2‐DMSO mediated approach to introduce −OCD3 into pyrroles in situ via multicomponent cascade cyclization reaction using methyl ketones, aniline, ethyl benzoylacetate and CD3OD as readily available substrates is reported. This process realizes introduction of −OCD3 into the Hantzsch pyrrole synthesis and synthesis of deuterated alkoxy‐substituted pyrroles with formation of one C−C bond, one C−O bond and two C−N bonds in one pot. Notably, this conversion has good substrate compatibility (62 examples) and eliminates of the need for anhydrous and anaerobic operation.

Review of application of the I2 and dimethyl sulfoxide combined reagent system to aryl methyl ketones for diverse transformations

“…Recently, our group proposed the one-pot synthesis of fully substituted pyrroles starting from methyl ketones, anilines, ethyl benzoyl acetate, and CD 3 OD through multicomponent cascade cyclization under the mediation of the I 2 –DMSO combined reagent. 56 More importantly, –OCD 3 can be introduced into the product in situ as a deuterium source (Scheme 46A). In this reaction, aniline preferentially reacts with ethyl benzoyl acetate to form an imine, whose C -nucleophilic center attacks the ketoaldehyde to form intermediate 46-1 .…”