Stereocontrol in Organic Synthesis Using the Diphenylphosphoryl Group

Abstract

In 1959, Horner showed that metalated alkyldiphenylphosphane oxides react with aldehydes or ketones to give alkenes. With this reaction, the diphenylphosphoryl (Ph 2 PO) group made its entrance into synthetic organic chemistry. In the thirty‐six years since that date, extensive research has shown that this olefination, the Horner–Wittig reaction, has unique properties that make it much more than simply the phosphane oxide cousin of the more famous phosphorus‐based olefinations—the Wittig reaction (based on phosphonium salts) and the Wadsworth–Emmons reaction (based on phosphonate esters). Early work on the Horner–Wittig reaction concentrated on the reactivity of phosphane oxides and the regioselectivity of their reactions, but more recently the power of the Ph 2 PO group to control the stereochemistry of alkenes, and to produce “on demand” either stereoisomer in high stereochemical purity, has emerged. From the study of these stereocontrolled Horner–Wittig reactions arose the realization that the Ph 2 PO group is useful not only for the control of the two‐dimensional stereochemistry of alkenes, but also of three‐dimensional stereochemistry in general. After a brief introduction to phosphane oxide chemistry, this review will examine the Horner–Wittig reaction, in both its original and “stereocontrolled” varieties. From there, we will move on to an account of the stereoselective construction of molecules containing the Ph 2 PO group, concentrating on the stereochemical directing effects of the Ph 2 PO group and on the role of its unique combination of attributes—steric bulk, electronegativity, and Lewis basicity—in controlling these reactions. Finally, we will present what is intended as a practical guide to this chemistry, covering the type of functionalized alkenes that have been made with the help of the Ph 2 PO group and giving guidelines that we hope will help the organic chemist to make the most of the chemistry the Ph 2 PO group has to offer. Still more can be expected from the Horner–Wittig reaction. Not only regioselective but also stereoselective Horner–Wittig additions and eliminations are possible with the bulky, anion‐stabilizing Ph 2 PO group. For example, alkenes having chiral centers on opposite ends of stereochemically defined double bonds can be constructed. Decisive advantages in these syntheses: Ph 2 PO compounds are simple to purify, and diastereomeric β‐hydroxy phosphane oxide adducts are easily separated.