THE KRAPCHO DEALKOXYCARBONYLATION REACTION OF ESTERS WITH α-ELECTRON-WITHDRAWING SUBSTITUENTS

摘要

Malonates and other α-activated esters, such as β-keto esters and α-cyano esters, are versatile intermediates in organic synthesis because the acidic nature of their α-hydrogens permits them to undergo a variety of reactions, such as alkyla-tion, electrophilic hydroxylation and animation, or the Michael and Knoevenagel reactions. In many synthetic schemes the removal of the activating ester group then becomes necessary at some point. This transformation can be done by conventional hydrolysis followed by thermal decarboxylation and re-esterification in the case of malonates. However, procedures are available that accomplish this process in one step and under conditions that tolerate the presence of a variety of functional groups and protecting groups. The subject of this chapter is the most widely used of these methods, which involves heating the substrates in a polar aprotic solvent, such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), or hexamethylphosphoric triamide (HMPA), usually in the presence of small amounts of water and/or an inorganic salt (Eq. 1). The process is variously referred to as the Krapcho reaction or Krapcho dealkoxycarbonylation. Several previous reviews, book chapters, and journal articles have dealt with synthetic applications and mechanistic aspects of the Krapcho dealkoxycarbonylation reaction. Other closely related methods that have found synthetic applications in dealkoxycarbonylations are discussed in the Comparison with Other Methods section and are included in the Tabular Survey with the exception of the palladium-catalyzed dealkoxycarbonylation of activated allyl and benzyl esters, which is briefly mentioned in the former but is not included in the latter. Occasionally reference is made in the subsequent sections to entries in the tables; these take the form (Table number-carbon-count-reference).