Recent developments in the use of catalytic asymmetric ammonium enolates in chemical synthesis.

Catalytic enantioselective transformations of carbonyl compounds via enolates that comprise the enolization and bond-forming step have received considerable attention within the synthetic organic chemistry community. Many of these methods have exploited the versatile properties of asymmetric Lewis acid complexes that display basic and/or acidic properties and have successfully lead to the development of a range of useful enantioselective processes. 1 In the last 6 years, the resurgence of interest in small organic molecules as catalysts has strongly impacted on the area of direct catalytic asymmetric enolate transformations. In particular, the use of nonracemic secondary amines as catalysts for the generation and reaction of enamines has resulted in a plethora of asymmetric processes that directly transform aldehydes and ketones into useful R-functionalized molecules. 3 However, in this case, the reaction manifold cannot accommodate the use of carbonyl functional groups such as esters, amides, nitriles, or other electron-withdrawing motifs. Therefore, the development of alternative methods for the direct formation of asymmetric enolate equivalents using other types of organic catalysts represents an important avenue of research in enantioselective catalysis. This review details the recent development of methods that use chiral tertiary amine catalysts as a source to generate asymmetric ammonium enolates. Historically, the cinchona alkaloids (Figure 1) have provided the most common source of these catalysts because they possess a catalytically active nucleophilic quinuclidine nitrogen atom that is embedded within a chiral environment, hence providing a well-defined molecular architecture that is a prerequisite for asymmetric induction.4 In addition to the naturally occurring cinchona alkaloids, planar chiral DMAP (4-N,N-dimethylaminopyridne) derivatives (Figure 1) can also be used as nucleophilic catalysts. Although these catalysts often require more complex synthesis, the corresponding “pyridinium” enolates often display enhanced reactivity compared to their cinchona alkaloid counterparts. 5