Mitsunobu Reaction with 4-(Diphenylphosphino)benzoic Acid: A Separation-Friendly Bifunctional Reagent that Serves as Both a Reductant and a Pronucleophile

Abstract

4-(Diphenylphosphino)benzoic acid was used for the Mitsunobu reaction as a bifunctional reagent that served as both a reductant and a pronucleophile. When combined with di-2-methoxyethyl azodicarboxylate, inversion of a secondary alcohol stereospecifically occurred to give an ester carrying a phosphine oxide group. The reaction mixture was directly hydrolyzed to give an inverted secondary alcohol in sufficient stereo and chemical purities by the presently developed chromatography-free process in conjunction with basic extraction, drying, and concentration.

Removal of Triphenylphosphine Oxide by Precipitation with Zinc Chloride in Polar Solvents

“…Reports on solutions to the problem of separating triphenylphosphine oxide (TPPO) byproducts in organic reactions fall into three broad categories: (1) improved methods for TPPO removal; (2) avoiding TPPO by using alternative phosphines 2 with more easily separated phosphine oxides, 3 and (3) avoiding stoichiometric phosphine oxide waste by developing reactions that are catalytic in phosphine 4 or do not require phosphine at all. 5 This report is focused on methods of TPPO removal, so strategies (2) and (3) will not be discussed further.…”