Facile Regiocontrolled Three-Step Synthesis of Poly-Substituted Furans, Pyrroles, and Thiophenes: Consecutive Michael Addition of Methyl Cyanoacetate to α,β-Enone, CuI-Mediated Aerobic Oxidation, and Acid-Catalyzed Paal-Knorr Synthesis

Abstract

An efficient synthesis of poly-substituted furans, pyrroles, and thiophenes was carried out in a regiocontrolled manner via a three-step process; (i) conjugate addition of methyl cyanoacetate derivatives to α,β-enones, (ii) CuI-mediated aerobic oxidation, and (iii) Paal-Knorr type synthesis of five-membered heterocycles.

OBO-Protected Pyruvates as Reagents for the Synthesis of Functionalized Heteroaromatic Compounds

“…Given their importance, a rich variety of methods have been developed for the synthesis of heteroarenes substituted with an α-acyl group (i.e., α to the heteroatom). These routes consist of traditional methods, such as the Paal–Knorr synthesis of pyrrole carboxylates from the appropriate α,δ-ketoester precursors or more modern approaches employing metal-catalyzed annulation, cycloaddition, , cyclocondensation, or insertion. − While many of these routes produce good results, the traditional syntheses are limited by the availability of the starting materials (e.g., α,δ-ketoesters) and more recent methods are sometimes hampered by the formation of regioisomers and/or by limitations in scope. Our experience in the de novo synthesis of heteroaromatic compounds using new catalytic methods, together with the general utility of α-acyl arene compounds, led us to design a new and extremely versatile route that would rely on catalytic enolate arylation methodology.…”