Aldol and Mannich-Type Reactions

Comprehendve Enantioselective Organocatalyds Catalysts Reactions, and Applications, First Edition. 

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It has also been shown that dimethylsilyl enolates can be activated by diisopropylamine and water and exhibit a high reactivity toward iV-tosyl imines to give Mannich-type reaction products in the absence of a Fewis acid or a Bronsted acid.51 For example, the reaction of [(1-cyclohexen-l-yl)oxy]dimethylsilane with 4-methyl-A -(phenylmethylene)benzene sulfonamide gave re/-4-methyl-N- (f )-[(15)-(2-oxocyclohexyl)phenyl-methyl] benzenesulfonamide (anti-isomer) in 91% yield stereoselectively (99 1 anti syn) (Eq. 11.30). On the other hand, Fi and co-workers reported a ruthenium-catalyzed tandem olefin migration/aldol and Mannich-type reactions by reacting allyl alcohol and imine in protic solvents.52... 

More recently, asymmetric Mannich-type reactions have been studied in aqueous conditions. Barbas and co-worker reported a direct amino acid catalyzed asymmetric aldol and Mannich-type reactions that can tolerate small amounts of water (<4 vol%).53 Kobayashi found that a diastereo- and enantioselective Mannich-type reaction of a hydrazono ester with silyl enol ethers in aqueous media has been successfully achieved with ZnF2, a chiral diamine ligand, and trifluoromethanesul-fonic acid (Eq. 11.31).54 The diastereoselective Mannich-type reaction... 

In 2004, Kobayashi reported for the first time Lewis acid-catalyzed organic reactions such as Aldol- and Mannich-type reactions proceeded smoothly in scCC>2 using PEG derivatives as surfactants. This could be the first attempt to use PEG as surfactant, facilitating the formation of emulsions in a single scCC>2 phase to synthesize small organic molecules [57]. 

Aldol and Mannich-Type Reactions 27 Table 2.6 (S)-Proline-catalyzed cross-aldol reactions of aldehyde donors.3)... 

Tandem Olefin-Migration/Aldol- and Mannich-Type Reactions.325... 

Aldol and Mannich-type reactions. Micellar systems favor aldol reactions and... 

BfCgFsls, an air-stable, water-tolerant Lewis acid catalyst, is applicable to conjugate additions of SEE and KSA to a,79-unsaturated ketones as well as aldol and Mannich-type reactions of silyl enolates [29]. 

Two palladium coordination complexes of 68 have been reported and used in asymmetric aldol and Mannich-type reactions. " Both the catalysts are recyclable although longer reaction times are needed on subsequent uses. Diamine ruthenium complexes bound to 68 have also been made and used in the asymmetric hydrogenation of ketones. ... 

Scandium triflate-catalyzed aldol reactions of silyl enol ethers with aldehyde were successfully carried out in micellar systems and encapsulating systems. While the reactions proceeded sluggishly in water alone, strong enhancement of the reactivity was observed in the presence of a small amount of a surfactant. The effect of surfactant was attributed to the stabiMzation of enol silyl ether by it. Versatile carbon-carbon bondforming reactions proceeded in water without using any organic solvents. Cross-linked Sc-containing dendrimers were also found to be effective and the catalyst can be readily recycled without any appreciable loss of catalytic activity.Aldol reaction of 1-phenyl-l-(trimethylsilyloxy) ethylene and benzaldehyde was also conducted in a gel medium of fluoroalkyl end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer. A nanostmctured, polymer-supported Sc(III) catalyst (NP-Sc) functions in water at ambient temperature and can be efficiently recycled. It also affords stereoselectivities different from isotropic solution and solid-state scandium catalysts in Mukaiyama aldol and Mannich-type reactions. 

In conclusion, an important amount of work has been done in the last 10 years to develop asymmetric control in the aldol- and Mannich-type reactions catalysed by chiral nickel complexes. This catalysis is intrinsically elegant and economical, but it appears that, at least for the time being, it is still limited to simpler substrates in most cases. In addition, further studies will have to focus on better understanding asymmetric control in these reactions. 

I 28 Aldol and Mannich-Type Reactions (a) Donor activation... 

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