An Efficient Synthesis of Aryl-Substituted Pyrroles by the Suzuki⁻Miyaura Coupling Reaction of SEM-Protected Pyrroles.

Keli Cui,Haihong Huang,Meng Gao,Hongyi Zhao,Dongfeng Zhang,Hong Yan

doi:10.3390/molecules24081594

Abstract

An efficient arylation of SEM-protected pyrroles by the Suzuki–Miyaura coupling reaction has been developed. The reaction can be carried out under mild conditions to provide aryl-substituted pyrroles in moderate to excellent yields. The scope and limitations of the methodology were evaluated, and the reaction was tolerant of a wide range of functionalities. Compared to the reported methods, the protocol has some advantages, such as commercially available materials, no debrominated by-products being formed, and the amine-protecting group being stable under the reaction conditions. The synthetic utility of the product has also been demonstrated, with several common transformations of the aryl-substituted pyrrole product being conducted. This protocol will offer the opportunity to explore other metal-catalyzed cross-coupling reactions employing SEM-protected pyrroles.

Highlights

Aryl-substituted pyrroles are an important structural motif in both pharmaceuticals and natural products alike, and display a wide range of interesting biological activities [1]
As our aim was to construct a small library of aryl-substituted pyrroles for biological activity assays, we found that it was inefficient to build these required pyrrole structures from some non-commercial starting materials
The coupling reaction is a powerful method in the formation of C(sp2 )–C(sp2 ) bonds, and the aryl-substituted pyrroles could be synthesized by the Stille–Migita cross-coupling reaction [15,16], decarboxylative coupling reaction [16, 17], metal-catalyzed desulfitative coupling reaction [18], and Suzuki–Miyaura coupling reaction [16]

Summary

Introduction

Aryl-substituted pyrroles are an important structural motif in both pharmaceuticals and natural products alike, and display a wide range of interesting biological activities [1]. There are a great deal of methods for the preparation of aryl-substituted pyrroles with this pendant ester group, and generally, the pyrrole core is formed from functionalized precursors with complex structures employing various catalysts and ligands [7,8,9,10,11,12,13,14]. As our aim was to construct a small library of aryl-substituted pyrroles for biological activity assays, we found that it was inefficient to build these required pyrrole structures from some non-commercial starting materials. If the aryl-substituted pyrroles could be synthesized from commercially available pyrrole compounds, the approach will be simple, straightforward, and efficient. The coupling reaction is a powerful method in the formation of C(sp2 )–C(sp2 ) bonds, and the aryl-substituted pyrroles could be synthesized by the Stille–Migita cross-coupling reaction [15,16], decarboxylative coupling reaction [16, 17], metal-catalyzed desulfitative coupling reaction [18], and Suzuki–Miyaura coupling reaction [16]

Objectives

Methods

Results

Conclusion