Poly(2-pyridyl)phosphines: Separation-Friendly Reagents for the Mitsunobu and Appel Reactions

Abstract

The use of bis(2-pyridyl)phenylphosphine and tris(2-pyridyl)phosphine as practical, drop-in alternatives to triphenylphosphine in the Mitsunobu and Appel reactions is reported. Their P-oxides are easily purged without chromatography via mild aqueous CuSO4 washes or direct filtration, circumventing the notoriously difficult removal of triphenylphosphine oxide. These orthogonal workup protocols preserve sensitive functionalities, enabling the multigram-scale synthesis of a complex nucleoside and streamlining the preparation of an advanced total synthesis intermediate.