"What have I got myself into, I can't deal with [this] the conversion of primary and secondary alcohols".
- Nicole Fox (Cycle 13)
The Mitsunobu Reaction allows the conversion of primary and secondary alcohols to esters, phenyl ethers, thioethers and various other compounds. The nucleophile employed should be acidic, since one of the reagents (diethylazodicarboxylate=DEAD) must be protonated during the course of the reaction to prevent from side reactions. Suitable nitrogen nucleophiles include phthalimide or hydrogen azide; subsequent hydrolysis or selective reduction makes the corresponding amines accessible.
DEAD = 
The triphenylphosphine combines with DEAD to generate a phosphonium intermediate that binds to the alcohol oxygen, activating it as a leaving group. Substitution by the carboxylate, mercaptyl, or other nucleophile completes the process.
The reaction proceeds with clean inversion, which makes the Mitsunobu Reaction with secondary alcohols a powerful method for the inversion of stereogenic centers in natural product synthesis.
New protocols have been developed which allow better removal of side products and/or the conversion of more basic nucleophiles.
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