Organocatalysis asymmetric aldol reactions

Other reviews deal with aldol additions of group 1 and 2 enolates,103 direct catalytic asymmetric aldol reactions catalysed by chiral metal complexes,104 the exploitation of multi-point recognition in catalytic asymmetric aldols,105 and recent progress in asymmetric organocatalysis of aldol, Mannich, Michael, and other reactions.106... 

ASYMMETRIC ORGANOCATALYSIS OF ALDOL REACTIONS 409 TABLE 6.11 Effect of Catalyst on the Direct Asymmetric Aldol Reaction"... 

A variety of catalytic ways of doing asymmetric aldol reactions have also been invented, but space prevents us discussing all but one. This one we highlight firstly because it illustrates the use of a supremely simple biologically derived compound to catalyse a complex reaction, and secondly because this discovery was part of the revolution in catalytic thinking which launched the field of organocatalysis in the early years of the 21st century. 

In the area of organocatalysis, proline has been utilised in various asymmetric reactions including direct asymmetric aldol reactions. Some such proline-catalysed aldol reactions, however, have serious limitations with respect to reactivity and selectivity. Although these problems were overcome through the development of new catalysts derived from proline, there is still an urgent need for structurally and electronically novel catalysts due to the difficulty in appropriate modification of proline. In this context, we have designed and prepared artificial amino acid catalyst (S)-l having a binaphthyl backbone as a frequently utilised chiral unit in asymmetric catalysts. ... 

Among the variety of organic transformations that are amenable to organocatalysis, the ring-forming reactions occupy a predominant position for efficient constructions of chiral carbo- and heterocycles [4]. In fact, the L-prolineintramolecular asymmetric aldol reaction of a triketone compound was reported by two industrial research groups as early as 1971 [5],... 

Current interest in organocatalysis is focused on asymmetric catalysis with chiral catalysts, or enantioselective organocatalysis (Fig. 2.42). In the asymmetric aldol reaction (Fig. 2.42), naturally occurring chiral proline is the chiral catalyst giving 93% enantiomeric excess when just 3% proline is added to an achiral triketone. 

Notz W, Tanaka F, Barbas CF (2004) Enamine-based organocatalysis with proline and diamines the development of direct catalytic asymmetric aldol, Mannich, Michael, and Diels-Alder reactions. Acc Chem Res 37(8) 580-591... 

Cobb, A.J.A., Shaw, D.M., Longbottom, D.A., Gold, J.B. and Ley, S.V. (2005) Organocatalysis with proline derivatives improved catalysts for the asymmetric Mannich, nitro-Michael and aldol reactions. Org. Biomol. Chem., 3, 84. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

This class of catalysts covers chemocatalysts that do not contain a transition metal. The class has been known for many years, but it is relatively recently that the term organocatalyst has been used (209). A wide variety of transformations can be performed, which is currently an area of intense research (209-218). Table 5 (220-252) summarizes some key transformations in which organocatalysis can be useful. Reactions range from the asymmetric epoxidation of alkenes, which need not be conjugated to another functional group, to aldol reactions and... 

Palomo C, Oiarbide M, Garcia JM. Current progress in the asymmetric aldol addition reaction. Chem. Soc. Rev. 2004 34 3-15. Ooi T, Maruoka K. Asymmetrix organocatalysis of structurally well-defined chiral quaternary ammonium fluorides. Acc. Chem. Res. 2004 37 526-533. 

Allemann C, Gordillo R, Clemente FR, Cheong PH-Y, Houk KN. Theory of asymmetric organocatalysis of aldol and related reactions rationalizations and predictions. Acc. Chem. Res. 2004 37 558-569. 

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