Oxidative coupling of sp2 and sp3 carbon\u2013hydrogen bonds to construct dihydrobenzofurans

Jiang-Ling Shi,Zhang-Jie Shi,Ding Wang,Yu-Qin Chen,Xi-Sha Zhang,Xiao-Lei Li,Yu-Xue Li

doi:10.1038/s41467-017-00078-6

Abstract

Metal-catalyzed cross-couplings provide powerful, concise, and accurate methods to construct carbon–carbon bonds from organohalides and organometallic reagents. Recent developments extended cross-couplings to reactions where one of the two partners connects with an aryl or alkyl carbon–hydrogen bond. From an economic and environmental point of view, oxidative couplings between two carbon–hydrogen bonds would be ideal. Oxidative coupling between phenyl and “inert” alkyl carbon–hydrogen bonds still awaits realization. It is very difficult to develop successful strategies for oxidative coupling of two carbon–hydrogen bonds owning different chemical properties. This article provides a solution to this challenge in a convenient preparation of dihydrobenzofurans from substituted phenyl alkyl ethers. For the phenyl carbon–hydrogen bond activation, our choice falls on the carboxylic acid fragment to form the palladacycle as a key intermediate. Through careful manipulation of an additional ligand, the second “inert” alkyl carbon–hydrogen bond activation takes place to facilitate the formation of structurally diversified dihydrobenzofurans.

Highlights

Metal-catalyzed cross-couplings provide powerful, concise, and accurate methods to construct carbon–carbon bonds from organohalides and organometallic reagents
We aimed to meet this challenge through a demonstration of the synthesis of versatile dihydrobenzofuran derivatives from readily available and simple phenyl alkyl ethers
As the directing strategy has proven efficient for single carbon–hydrogen bond activation[21, 22] and the intramolecular aliphatic carbon–hydrogen bond activations have been shown effective from in-situ-generated Pd(II) complexes from an oxidative addition of aryl halides with Pd(0) catalysts[23], we conceived that a new strategy for reaching our target may be through ligand-manipulated tandem carbon–hydrogen activations (Fig. 1d)

Summary

Introduction

Metal-catalyzed cross-couplings provide powerful, concise, and accurate methods to construct carbon–carbon bonds from organohalides and organometallic reagents. With or without directing groups, aryl carbon–hydrogen bonds play key roles as surrogates of aryl halides in couplings with various organometallic reagents under oxidative conditions[4, 5]. The goal is to develop efficient oxidative coupling protocols to construct carbon–carbon bonds between both “inert” aromatic and aliphatic carbon–hydrogen bonds.

Objectives

Results

Conclusion