Development of a Catalytic Ester Activation Protocol for the Efficient Formation of Amide Bonds using an Ar−I/HF⋅pyridine/ mCPBA System

Abstract

A new catalytic approach for the activation of esters, that possess a p-hydroxyphenyl group as a potential activating group on the ester residue, was developed and applied to the efficient synthesis of amides and peptides. A characteristic feature of this protocol is the in-situ generation of a hypervalent iodine(III) species using an ArÀ I/HF•pyridine/ mCPBA system. A reactive acyl fluoride intermediate is smoothly generated via the oxidative dearomatization of phenols in the presence of a catalytic amount of 4iodoanisole, thereby affording various amides and peptides including sterically hindered derivatives.

Efficient Amide Formation from Non‐Activated Cyclopropyl Ester via Acyl Fluoride Generation Using Hypervalent Iodine(III) Reagent and Selectfluor

“…We also exploited the facile dearomatization of the phenol moiety promoted by a hypervalent iodine(III) reagent to activate p ‐hydroxyphenyl esters and subsequently generate an acyl fluoride intermediate using pyridine ⋅ hydrogen fluoride (Py ⋅ 9HF) under mild conditions (Scheme 1b) [17] . Later, this protocol was successively developed as a catalytic reaction using an iodoarene/ m ‐chloroperoxybenzoic acid ( m CPBA)/Py ⋅ 9HF hybrid system [18] . These methods utilized the reactive benzylic proton of the p ‐methoxybenzyl group and nucleophilic alcohol of the p ‐hydroxyphenyl group which could potentially participate in unwanted reactions during the synthetic process.…”

“…[17] Later, this protocol was successively developed as a catalytic reaction www.asianjoc.org using an iodoarene/m-chloroperoxybenzoic acid (mCPBA)/ Py • 9HF hybrid system. [18] These methods utilized the reactive benzylic proton of the p-methoxybenzyl group and nucleophilic alcohol of the p-hydroxyphenyl group which could potentially participate in unwanted reactions during the synthetic process. In this paper, we wish to report an intriguing activation method for non-activated cyclopropyl esters promoted by a hypervalent iodine(III) reagent and Selectfluor.…”