Synthesis of Diverse Pentasubstituted Pyrroles by a Gold(I)-Catalyzed Cascade Rearrangement-Cyclization of Tertiary Enamide

Abstract

An efficient Au­(I)-catalyzed intramolecular cascade reaction of tertiary enamides tethered an alkynyl group has been developed. The process is composed of a propargyl-claisen rearrangement and 5-exo-dig cyclization. This protocol provided a powerful method for the preparation of a variety of pentasubstituted pyrroles derivatives with excellent functional group tolerance in excellent yields. Scale-up experiment and chemical transformations of products exhibited the versatility of tertiary enamides in organic synthesis again.

Recent progress in the homogeneous gold-catalysed cycloisomerisation reactions

“…A proposed mechanism is shown in Scheme 52. Xueyuan Wang 58 reported an efficient and novel method for forming polysubstituted pyrroles from tertiary enamides containing the propargyl group using the Au(I) catalyst through the Claisen rearrangement and 5-exo cyclization (Scheme 53). The optimised conditions show that the [(JhosPhos)AuCl] catalyst in HFIP solvent under an N 2 atmosphere gave 96% yield of the desired product.…”

Chiral Trifluoromethylated Enamides: Synthesis and Applicability

“…The pinacolborane moiety would provide another opportunity for other potential transformations. Next, alkylation to the respective tertiary enamide followed by a Au-catalyzed cyclization step, according to the conditions by Xu and co-workers, 72 iii. iv.…”

Advancements in Gold‐Catalyzed Cascade Reactions to Access Carbocycles and Heterocycles: An Overview

“…Xu group reported a synthetic route to pentasubstituted pyrroles via gold(I)‐catalyzed intermolecular cascade reaction (Scheme 30). [67] The reactions proceed through propargyl‐Claisen rearrangement and 5‐exo‐dig cyclization. Tertiary enamides containing alkyne precursor 79 treated with 2.5 mol% gold‐catalyst in hexafluoroisopropanol under nitrogen atmosphere at room temperature for 20 min and afforded 60–98 % yield of the desired product 80 .…”