Aldol reactions organocatalysed

Fteproduced from GuiSena G, del Carmen Hita M. Nijera C, Vidzquez SF Solvent-free asymmetric direct aldol reactions organocatalysed by recoverable (SJ-binam-L-prolinamide. Tetrahedron Asymm 2007 18 2300-4. Copyright (2007). with permission from Elsevier. 

If maximizing catalyst hydrophobicity is the key to success in the organocatalysed aldol reaction under liquid/liquid biphasic aqueous conditions using catalysts 3-16, this property does not generally provide practical recycling procedures. 

Organocatalysed aldol reaction has been extensively studied after being rediscovered in 2000 when List et al. developed the first proline-catalysed asymmetric direct intermolecular reaction. The aldol process is defined as the reaction of two carbonyl compounds to produce p-hydrojq carbonyl derivatives, and many combinations of starting compounds could be envisaged, but the most studied are summarised in Scheme 6.1. 

In contrast to aldol reactions, the major diastereoisomer formed in the Mannich reaction has syn configuration, because the orientation of the imine is opposite to that of the carbonyl in the transition state (figure C in Scheme 6.5). Carter et al. reported an organocatalysed domino Mannich-aza-Michael reaction for accessing nitrogen-containing [2.2.2]-bicyclic scaffolds promoted by 15e, in a highly enantioselective and diastereoselective manner (eqn. (3) in Scheme 6.5). 

Hartikka and Arvidsson demonstrated the high catalytic efficiency of catalyst 5a for the direct aldol reaction of acetone with various aldehydes. In the organocatalysed direct asymmetric aldol reaction, acetone reacted with aromatic and aliphatic aldehydes, resulting in formation of p-hydro) ketones with good yields and moderate to high enantiomeric excesses (Scheme 9.9). ... 

Scheme 19.62 Organocatalysed domino Michael-aldol reaction for the construction of bispiro-oxindoles.

Even among organocatalysed-mediated aldol reactions, there is only one successful reaction of acetaldehyde in spite of extensive research on this class of reactions in recent years." Indeed, this unique example, reported by Hayashi et al., described the highly enantioseleetive aldolisation of acetaldehyde with various aldehydes catalysed by a diarylprolinol as the organoca-talyst." This reaction was performed in DMF and provided the corresponding p-hydroxy a-unsubstituted aldehydes, whieh were subsequently reduced into... 

Cinchona-alkaloid-catalysed conjugate cyanation of enones has enabled the synthesis of trifluoromethyl-substituted diarylpyrroles with ee<96%P° Thiochro-manes have been formed by asymmetric domino sulfa-Michael-aldol reactions of 2-mercaptobenzaldehyde with a,/ -unsaturated A-acylpyrazoles. Asymmetric organocatalysed oxy-Michael addition to y-hydroxy a,/ -unsaturated thioesters on reaction with t-BuCHO has been used to form -hydroxy carbonyl compounds HOCH2C H(OH)CH2CO.SAr via cyclic hemiacetal intermediates. 

The first experiments of an organocatalysed aldol condensation between acetone and 4-nitrobenzaldehyde with aliphatic amino acids in anhydrous conditions (DMSO acetone 4 l) led to the desired adduct in very low yields (<10%). In 2005, Amedjkouh and Cordova independently showed the importance of additional water in the reaction medium to improve the yields. The concept was based on the hypothesis that a molecule of water would participate in a proton relay in the aldolase system, and would allow for a faster hydrolysis of the intermediates. A hydrophobic amino acid might be efficient in aqueous media by strong association with hydrophobic reactants. Furthermore, water would restore the catalyst from its deactivation by condensation with the aldehyde. 

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