Mitsunobu Reaction

Abstract

Abstract The alkylation of compounds with active protons by using primary or secondary alcohols as the alkylating agents in combination with triphenylphosphine and diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD), to form molecules like esters, ethers, thioethers, and amines is generally known as the Mitsunobu reaction. In addition, the specific reaction for forming esters by means of DEAD (or DIAD) and PPh3 is generally referred to as the Mitsunobu esterification. It is known that this reaction begins with the formation of a relatively stable betaine, called the Morrison–Brunn–Huisgen intermediate. This reaction is also evidenced to undergo through a radical mechanism. When secondary alcohols are used as alkylating agents, the stereochemistry is generally inverted via the Walden inversion, because of the nature of S N 2 displacement. The study finds that triphenylphosphine oxide and dialkyl hydrazinedicarboxylate cannot be avoided in this reaction, which often prevents the desired products from being isolated.