Generation of Aryl Radicals from Aryl Hydrazines via Catalytic Iodine in Air: Arylation of Substituted 1,4-Naphthoquinones.

Saibal Sar,Subhabrata Sen,Jyoti Chauhan

doi:10.1021/acsomega.9b04014

Abstract

Arylated building blocks or heterocycles are key to myriad applications, including pharmaceutical drug discovery, materials sciences, and many more. Herein, we have reported a mild and efficient strategy for generation of aryl radicals by reacting appropriate aryl hydrazines with catalytic iodine in open air. The aryl radicals were quenched by diversely substituted 1,4-napthoquinones present in the reaction mixture to afford diversely substituted 2,3-napthoquinones in moderate to excellent yield. Control experiments provided insights into the putative reaction mechanism.

Highlights

Aryl radicals are highly reactive intermediates that play a crucial role in diverse organic transformations, such as halogen-transfer biaryl couplings, Sandmeyer reactions, addition to iminium ions, addition to sulfur dioxide, and reactions with electron-deficient alkenes (Meerwein’s arylation) and alkynes.1a−k Due to their versatile utility, there have been quite a few synthetic strategies to generate them
Aryl radicals are generated by treating aryl hydrazines or aryl hydrazine hydrochlorides with bases in the presence of air.5a−c These aryl radicals are eventually quenched by various heteroaromatic or heterocycle building blocks, such as pyrrolidine, pyridine, chromones, etc., to provide the corresponding arylated species.5a−c. By virtue of their ubiquitous presence in nature and their role as inhibitors in diverse biological systems, such as bacteria, fungi, mammals, and parasites, naphthoquinones hold a niche position in synthetic and medicinal chemistry.6a−k They have displayed diverse activities as antibiotic, antifungal, anti-inflammatory, anti-allergic, apoptotic, and antithrombotic agents.6a−e Aryl naphthoquinones form an exclusive class of natural products and are found as building blocks in crisamicin A, microphyllaquinone, conocurvone, etc.6f−k
We demonstrate the generation of aryl radicals from catalytic iodine in an open air vessel, with trifluoroethanol (TFE) as a solvent at 40 °C

Summary

Introduction

Aryl radicals are highly reactive intermediates that play a crucial role in diverse organic transformations, such as halogen-transfer biaryl couplings, Sandmeyer reactions, addition to iminium ions, addition to sulfur dioxide, and reactions with electron-deficient alkenes (Meerwein’s arylation) and alkynes.1a−k Due to their versatile utility, there have been quite a few synthetic strategies to generate them. Reactions with 1 equiv of tetrabutylammonium iodide (TBAI) (in ACN/H2O = 1:3 solvent system) and molecular iodine (I2) (with ACN as solvent) drastically improved the yield to ∼75% (Table 1, entries 5 and 6).

Results

Conclusion