One of the most powerful reactions in organic chemistry is the Mitsunobu reaction, which, due to its simplicity, mildness and convenience, has become an extremely important tool for the conversion of an alcohol to a variety of functional groups, such as esters, ethers, sulfonamides and imides. Indeed, the Mitsunobu reaction features heavily in the syntheses of our a-helix mimetics designed to inhibit the oncoprotein Mcl-1. The Mitsunobu reaction employs an azodicarbonyl species (typically diisopropyl azodicarboxylate (DIAD)) and a phosphine (typically triphenylphosphine (PPh3)) as co-reagents to generate the requisite betaine intermediate in situ. However, the major caveat of the Mitsunobu reaction is purification, as reduced DIAD (DIAD-H2) and oxidized PPh3 (Ph3P=O) often contaminate the product. As part of our continued interest in the Mitsunobu reaction, we have investigated the scope of the water-soluble Mitsunobu reagent azodicarbonyl dimorpholide (ADDM). Furthermore we will present optimized conditions for a chromatography-free Mitsunobu reaction with ADDM.

Towards chromatography-free Mitsunobu reactions with the versatile and water-soluble Mitsunobu reagent azodicarbonyl dimorpholide (ADDM)

246th National Meeting (2013)

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