Phosphorus Addition at sp² Carbon

Engel, Robert


In recent years a renewed interest in the synthesis of organophosphorus compounds has appeared. This has been the result principally of the development of new applications of materials bearing a carbon–phosphorus linkage for chemical synthesis, biological regulation, and a variety of industrial uses.

In chemical syntheses the phosphoryl function has been found to be of great utility as an activator for two major categories of transformations. The first of these is the generation of new carboncarbon double bonds through the phosphoryl-stabilized anion modifications of the Wittig reaction. For these reactions, the phosphoryl function increases the acidity of the hydrogen of the carbon attached to phosphorus and, after addition to a carbonyl linkage, is usually eliminated as a water-soluble byproduct. Alternatively, the initially formed phosphonate anion may be used as a nucleophile in a substitution reaction leading to a derived phosphonate product having its own synthetic utility.

In the second category of transformations an appropriately functionalized phosphonate reacts at the carbon attached to phosphorus to give products that can be envisioned as resulting from reaction of an electrophilic substrate with a carbonyl group of inverted polarity. The phosphoryl function, which is generally eliminated in the formation of the target material, facilitates these “umpolung” reactions that could not be accomplished directly with a parent material bearing the simple carbonoxygen double bond.

With regard to biological applications, the synthesis of organophosphorus compounds has been of interest for several reasons. Among these is the discovery in a variety of organisms of naturally occurring compounds bearing the carbonphosphorus bond. Phosphonomycin and aminoethylphosphonic acid are two well-known examples of such compounds. It has also been recognized that phosphonates may be capable of perturbing metabolic processes normally involving phosphates of similar structure. In addition, materials with other metabolic regulatory capabilities have been found. As a result, there have been not only syntheses of many new organophosphorus compounds but also the development of improved methods for such syntheses.

The review presented in this chapter is concerned with one approach to carbonphosphorus bond formation that is particularly significant for the aforementioned applications, specifically the addition of a (formally) trivalent phosphorus ester or amide to an unsaturated carbon linkage under polar reaction conditions. Reactions of a variety of types of phosphorus reagents with simple carbonyl compounds, imines, and other related polar unsaturated carbon functions, as well as conjugate addition reactions, are reviewed.