Mitsunobu Reaction

Introduction

The Mitsunobu reaction was discovered by a professor in Japan, Oyo Mitsunobu (1934–2003). Mitsunobu reaction is an organic reaction that transforms primary or secondary alcohol into thioethers, phenyl ethers, esters, and various other compounds using an azodicarboxylate such as diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD) and triphenylphosphine.

Mitsunobu Reaction

Reaction mechanism

Reaction Mechanism of Mitsunobu Reaction

The reaction mechanism of the Mitsunobu reaction is a bit complex. The mechanism begins by forming a zwitter ionic intermediate on DEAD by an action of \(PPh_{3}\). The alcohol binds to the nucleophile and phosphonium ion to perform \(S_{N}2\) to yield the final substitution product.

The reaction has been applied in the synthesis of aryl ethers.

Synthesis of aryl ethers

The conversion with DEAD with particular reactants fails as phenol is a weaker acid. Azo dicarbonyl di piperidine (ADDP) is used instead of it as a stronger base, wherein phosphine as polymer-supported triphenylphosphine \(PS-PPh_{3}\).. This reaction is used to synthesize colchicine, quinine, morphine, sarain, eudistomin, stigma tellin, strychnine, nupharamine, and oseltamivir.

Leave a Comment

Your email address will not be published. Required fields are marked *