Separation-friendly Mitsunobu reactions: a microcosm of recent developments in separation strategies

The Mitsunobu reaction is famous for its scope and power, but infamous for its separation headaches. Typically, the target product is enticed away from the reagent-derived byproducts by careful chromatography. The use of polymer-bound Mitsunobu reagents solves only half of the problem, because polymer-bound diethyl azodicarboxylate (DEAD) and phosphine reagents cannot be employed simultaneously. This article classifies, compares, and contrasts various emerging strategies for product isolation in Mitsunobu reactions. Because so many different strategies have been used, the Mitsunobu reaction is a microcosm for the new field of strategy level separations.