Synthetic Applications of Phosphoryl-Stabilized Anions

Wadsworth, William S., Jr.


The successful synthesis of a wide variety of unsaturated compounds by treatment of phosphoranes with carbonyl compounds (the Wittig reaction) has stimulated the search for other synthetic methods that employ organophosphorus reagents. One of the most fruitful results has been the discovery that phosphoryl-stabilized carbanions have wide applicability in the preparation of unsaturated compounds and offer significant advantages over conventional procedures.

This review discusses the chemistry of carbanions stabilized by delocalization of their negative charge by means of a P(O) group. Carbanions obtained by treating phosphine oxides, phosphinates, and phosphonates, with a base have been explored in depth. In particular, the phosphonates have found great popularity because of their availability and ease of application. The use of Wittig-type reagents in synthesis has been reviewed and is not mentioned except by way of comparison.

Carbanions prepared from phosphinates have no known advantage over those prepared from phosphonates or phosphine oxides. Those carbanions obtained from phosphine oxides will be considered here only in the way of comparison.

Anions that have their negative charge located on an atom adjacent to a P(O) group gain stability owing to delocalization of the charge through the phosphoryl group. Although the exact nature of the delocalization is not well defined, the ability of phosphorus to become pentacovalent by use of its d orbitals is undoubtedly a contributing factor. It should be noted that the P(O) group is generally not so effective as the carbonyl group in stabilizing a negative charge. If other stabilizing groups are not present, formation of P(O)-stabilized carbanions generally requires more basic conditions than does the removal of a proton from a carbon atom alpha to a carbonyl group.

Horner and co-workers were the first to investigate the synthetic utility of P(O)-stabilized carbanions. The utility of phosphonate carbanions as synthetic intermediates was expanded by the discovery that, as olefin-forming reagents, phosphonates have certain advantages over both phosphoranes and phosphine oxides. As a result, the method has found favor because of the availability of reagents, ease of workup, and convenient reaction conditions. In particular, the reactivity of phosphonate carbanions has been taken advantage of in numerous ways. As indicated by a number of reviews, these carbanions have become one of the most frequently employed organophosphorus reagents.

The utility of phosphoryl-stabilized anions is apparent from the variety of materials that can be prepared by suitable structural modifications. Besides simple monoolefins and polyenes, a partial list would include allenes, unsaturated amides, aldehydes, esters, sulfides, sulfones, and nitrogen compounds such as imines, isocyanates, and ketenimines. In addition to their convenience for introducing unsaturation, these stabilized anions offer routes to cyclopropanes and heterocyclic systems. In this chapter, reactions that are of unusual interest are discussed separately; more routine reactions are included only in the tabular survey.

Olefin formation by means of phosphonate carbanions has been referred to as the Horner-Emmons or Wadsworth-Emmons modification of the Wittig reaction, whereas the use of phosphine oxide or phosphinate carbanions is generally referred to as the Horner modification. In order to prevent confusion and to avoid misdirecting credit, proper names are omitted and the synthesis of an olefin by phosphonate carbanions is termed phosphonate-olefin formation. Likewise, the term phosphine oxide-olefin formation is employed where appropriate.