Ru(ii)-catalyzed C6-selective C-H acylmethylation of pyridones using sulfoxonium ylides as carbene precursors.

Yangjie Fu,Jiang Wang,Xiaoling Bi,Qiyu Zhang,Zhiyu Li,Zhaohui Wang,Hong Liu

doi:10.1039/c9ra10749e

Abstract

In this study, we describe a method using sulfoxonium ylides as carbene precursors to achieve C6-selective acylmethylation of pyridones catalyzed by a ruthenium(ii) complex. This approach featured mild reaction conditions, moderate to excellent yields, high step economy, and had excellent functional group tolerance with good site selectivity. Besides, gram-scale preparation, synthetic utility, and mechanistic studies were conducted. It offers a direct and efficient way to synthesize pyridone derivatives.

Highlights

Pyridone is exhibited as a privilege scaffold in a large range of biological active agents, attracting much attention from medicinal chemists (Fig. 1).[1]
Only limited examples have been reported on the direct C–H bond functionalization on C6 position of pyridone.[5]
Cramer and collaborators described the synthesis of 1,6-annulated 2-pyridones by selective intramolecular nickel catalyzed cyclization.5c A erwards, more C–H functionalization at C6 position of pyridone mediated by transition-metal have been reported.[6]

Summary

Introduction

Pyridone is exhibited as a privilege scaffold in a large range of biological active agents, attracting much attention from medicinal chemists (Fig. 1).[1]. The direct alkylation of pyridone was usually afforded by pre-functionalization with a halogen followed by transition-metal catalyzed coupling reactions. The direct C–H functionalization strategy to form C–C or C–X bonds has become a more effective and reliable synthetic route.[2] Transition-metal-promoted C3

Results

Conclusion