Mitsunobu reaction

<p>The Mitsunobu reaction is an <a href="/facts/Organic_reaction/SESmeGWm">organic reaction</a> that converts an alcohol into a variety of functional groups, such as an <a href="/facts/Ester/FoUAIIw4">ester</a>, using <a href="/facts/Triphenylphosphine/nYFNCVcJ">triphenylphosphine</a> and an azodicarboxylate such as <a href="/facts/Diethyl_azodicarboxylate/3zvKd7sw">diethyl azodicarboxylate</a> (DEAD) or <a href="/facts/Diisopropyl_azodicarboxylate/SkYYwGBK">diisopropyl azodicarboxylate</a> (DIAD). Although DEAD and DIAD are most commonly used, there are a variety of other azodicarboxylates available which facilitate an easier workup and/or purification and in some cases, facilitate the use of more basic nucleophiles. It was discovered by Oyo Mitsunobu (1934–2003). In a typical protocol, one dissolves the alcohol, the carboxylic acid, and triphenylphosphine in <a href="/facts/Tetrahydrofuran/P5t6SkMK">tetrahydrofuran</a> or other suitable solvent (e.g. <a href="/facts/Diethyl_ether/Ep20vEdj">diethyl ether</a>), cool to 0 °C using an ice-bath, slowly add the DEAD dissolved in THF, then stir at room temperature for several hours. The alcohol reacts with the phosphine to create a good leaving group then undergoes an <a href="/facts/Walden_inversion/6p72etqF">inversion</a> of <a href="/facts/Stereochemistry/XkcRVNwd">stereochemistry</a> in classic SN2 fashion as the nucleophile displaces it. A common side-product is produced when the azodicarboxylate displaces the leaving group instead of the desired nucleophile. This happens if the nucleophile is not acidic enough (<a href="/facts/Acid_dissociation_constant/t4YyRtKC">pKa</a> larger than 13) or is not nucleophilic enough due to steric or electronic constraints. A variation of this reaction utilizing a nitrogen nucleophile is known as a Fukuyama–Mitsunobu.
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<p>Several reviews have been published.
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Mitsunobu reaction open-in-new

Mitsunobu reaction