The direct catalytic asymmetric aldol reaction

Abstract

Asymmetric aldol reactions are a powerful method for the construction of carbon-carbon bonds in an enantioselective fashion. Historically this reaction has been performed in a stoichiometric fashion to control the various aspects of chemo-, diastereo-, regio- and enantioselectivity, however, a more atom economical approach would unite high selectivity with the use of only a catalytic amount of a chiral promoter. This critical review documents the development of direct catalytic asymmetric aldol methodologies, including organocatalytic and metal-based strategies. New methods have improved the reactivity, selectivity and substrate scope of the direct aldol reaction and enabled the synthesis of complex molecular targets

Ionic Liquid Immobilized Organocatalysts for Asymmetric Reactions in Aqueous Media

“…The direct crossed-aldol reaction is considered to be one of the key transformations for carbon-carbon bond formation [47,[75][76][77][78]. However, acetaldehyde, which is considered the simplest of the enolizable carbonyls, is known to be very reactive due to the fact that various undesired side products of poly-aldolization, dehydration, Tishchenko-type processes and oligomerization are formed [79].…”

Gelatin Protein‐Mediated Direct Aldol Reaction

“…It should be noted that these values might vary depending on the source of the material and processing method [6]. The fact that some amino acids and peptides have been employed in different catalytic studies [2][7] motivated us to explore the potential ability of gelatin to promote some organic reactions. This protein has been traditionally used as a general ingredient in food, cosmetic, pharmaceutical and photographic industries [8], and only recently as a reducing ligand in the preparation of metal nanoparticles [9].…”

Solvent-Free Enantioselective Friedländer Condensation with Wet 1,1′-Binaphthalene-2,2′-diamine-Derived Prolinamides as Organocatalysts

“…15 Only recently, catalytic asymmetric versions of this reaction, consisting in the condensation of 2-aminoaryl aldehydes with a carbonyl compounds, were reported, either using enamine catalysis mediated by trans-4-hydroxyproline, [16][17] or a chiral phosphoric acid derivative in combination with an achiral amines 18 as promoters, both in high levels of enantioselectivities. Although, the organocatalyzed aldol reaction [19][20][21][22][23][24][25] has been deeply studied in the last ten years, only a few reports dealing with the desymmetrization of the prochiral ketones [26][27][28][29][30][31][32][33][34][35][36][37] used as nucleophiles, which is one of the prerequisite for the success of the synthesis of the chiral quinoline analogues, have been reported. Furthermore, the synthesis of the quinolines required the use of o-aminobenzaldehydes as electrophiles, which are less reactive than the generally activated aromatic aldehydes used in the enamine-catalyzed aldol reaction.…”