Abstract

Among the most important of all carbon–carbon bond forming methods are reactions of electrophiles with organolithium compounds. As part of this large group of reagents, regio- and stereoselectively prepared alkenyllithiums are valuable intermediates for the controlled construction of a wide variety of substituted alkenes. This chapter covers a highly selective procedure for the preparation of relatively complex alkenyllithium species from ketone arenesulfonylhydrazones. The reaction of these vinyl anions with various electrophiles affords a wide range of specifically substituted di-, tri-, and tetrasubstituted alkenes.

This methodology arose from early studies on the thermal decomposition of sodium salts of p-toluenesulfonylhydrazones (tosylhydrazones) and two subsequent modifications of that reaction. In the early 1950s Bamford and Stevens reported a new reaction based on the thermally induced decomposition of ketone tosylhydrazone monosodium salts, producing products derived either from carbene intermediates (aprotic conditions) or carbocations (protic conditions). The protic reaction is of marginal synthetic value because mixtures of carbocation-derived products are normally obtained; however, the aprotic reaction has found widespread use in the synthesis of multicyclic, strained hydrocarbons. Both reactions have been covered in reviews.

It was later found that treating a tosylhydrazone with ethereal alkyllithium, instead of the much weaker alkoxide bases used previously, results in a very different reaction. Under these conditions an alkene derived from an alkenyllithium intermediate is the sole product. This process, commonly known as the Shapiro reaction, has been applied to the preparation of a large number of structurally diverse alkenes and is the subject of an earlier review. Unfortunately, trapping of the vinyllithium intermediate proved to be so inefficient and unpredictable under a number of different conditions that the reaction was of little utility as a method of vinyllithium generation. In 1975, however, conditions were reported that not only gave high yields of olefin but also nearly quantitative incorporation of electrophiles. The only remaining drawback was that efficient trapping of tosylhydrazone-derived vinyllithiums occurs only with the use of excess base (≥3 equivalents of n-butyllithium) rather than the stoichiometric 2 equivalents required by the mechanism, even though the olefin yield was quite good. Eventually, this nagging stoichiometry problem, which necessitates the use of excess electrophile as well as excess base, was solved by the use of ketone 2,4,6-triisopropylbenzenesulfonylhydrazones (trisylhydrazones) in place of tosylhydrazones. An account of some synthetically useful aspects of the Shapiro reaction and its subsequent variants has appeared.

This review covers the generation of vinyllithiums from arenesulfonylhydrazones under conditions that allow efficient trapping with electrophiles other than proton sources. Examples in which trapping of the intermediate vinyllithium was not demonstrated, including reactions conducted under standard “Shapiro reaction” conditions, are excluded.