Iron-Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl Chlorobenzenesulfonates.

Elwira Bisz

doi:10.3390/molecules26195895

Abstract

Aryl sulfonate esters are versatile synthetic intermediates in organic chemistry as well as attractive architectures due to their bioactive properties. Herein, we report the synthesis of alkyl-substituted benzenesulfonate esters by iron-catalyzed C(sp2)–C(sp3) cross-coupling of Grignard reagents with aryl chlorides. The method operates using an environmentally benign and sustainable iron catalytic system, employing benign urea ligands. A broad range of chlorobenzenesulfonates as well as challenging alkyl organometallics containing β-hydrogens are compatible with these conditions, affording alkylated products in high to excellent yields. The study reveals that aryl sulfonate esters are the most reactive activating groups for iron-catalyzed alkylative C(sp2)–C(sp3) cross-coupling of aryl chlorides with Grignard reagents.

Highlights

Cross-coupling reactions are considered to be a fundamental tool in modern organic synthesis [1,2,3]
Iron catalysis is of great interest in cross-coupling reactions due to the abundance of iron in the earth’s crust, its low toxicity, and easy removal of iron salts from post-reaction mixtures [4,5,6,7,8,9,10,11,12,13]
The present study extends extends the scope of benign iron-catalyzed cross-couplings to chlorobenzenesulfonate the scope of benign iron-catalyzed cross-couplings to chlorobenzenesulfonate electroelectrophiles using benign urea ligands as replacement for toxic NMP

Summary

Introduction

Cross-coupling reactions are considered to be a fundamental tool in modern organic synthesis [1,2,3]. In this context, iron catalysis is of great interest in cross-coupling reactions due to the abundance of iron in the earth’s crust, its low toxicity, and easy removal of iron salts from post-reaction mixtures [4,5,6,7,8,9,10,11,12,13]. Iron-catalyzed cross-couplings have attracted significant attention in the pharmaceutical industry [16], where they have become competitive with palladium catalysts, which have historically dominated this field [17,18,19]. Recent reports presented by us showed that NMP can be successfully replaced with other benign amide-type donors (conjugation of Nlp to C=O) [21,22,23,24]

Methods

Results

Conclusion