Asymmetric catalysis Mannich-type reaction

Lewis acids as water-stable catalysts have been developed. Metal salts, such as rare earth metal triflates, can be used in aldol reactions of aldehydes with silyl enolates in aqueous media. These salts can be recovered after the reactions and reused. Furthermore, surfactant-aided Lewis acid catalysis, which can be used for aldol reactions in water without using any organic solvents, has been also developed. These reaction systems have been applied successfully to catalytic asymmetric aldol reactions in aqueous media. In addition, the surfactant-aided Lewis acid catalysis for Mannich-type reactions in water has been disclosed. These investigations are expected to contribute to the decrease of the use of harmful organic solvents in chemical processes, leading to environmentally friendly green chemistry. 

In addition, quite recently a direct catalytic asymmetric Mannich-type reaction has been achieved by the cooperative catalysis of ALB and La(0Tf)3-nH20. 

Matsunaga S, Kumagai N, Harada S, Shibasaki M (2003) anti-Selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing beta-amino alcohols. J Am Chem Soc 125 4712—4713 Mayer S, List B (2006) Asymmetric counteranion-directed catalysis. 

The Mannich reaction and its variants have been reviewed, mainly focussing on asymmetric catalysis thereof. Catalytic, enantioselective, vinylogous Mannich reactions have also been reviewed, covering both direct and silyl dienolate methods. Another review surveys Mannich-type reactions of nitrones, oximes, and hydrazones. A pyrrolidine-thiourea-tertiary amine catalyses asymmetric Mannich reaction of N-Boc-imines (e.g. Ph-Ch=N-Boc) with ethyl-4-chloro-3-oxobutanoate to give highly functionalized product (16). Addition of triethylamine leads to one-pot intramolecular cyclization to give an 0-ethyl tetronic acid derivative (17). ... 

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. 

The asymmetric synthesis of nemonapride 92 was achieved by applying the Mannich-type reaction of the Schiff base 1 with A-Boc aliphatic imine 93 under the phase-transfer catalysis of (S,S)-TaDiAS (PTC 11) (Scheme 4.22)." The differently protected a,(3-diamino acid ester 94 was isolated in 72% yield with 65% ee, which was then transformed into the stereochemicaUy pure pyrrolidine derivative 95, an important precursor of the target 92. 

Mannich reactions give rise to (i-amino carbonyl compounds which are amenable to further synthetic manipulations. Numerous stereoselective variants have been achieved by means of different types of catalysts including both metal complexes and organic molecules. In 2004, the groups of Akiyama and Terada independently selected this transformation as a model reaction for the introduction of a novel chiral motif to asymmetric catalysis [14, 15]. 

The classical reactions that are usually associated with asymmetric enamine catalysis are aldol and Mannich-type... 

In conclusion, Kappe s group demonstrated the absence of any differences between conventional and microwave heating in proline-catalyzed Mannich and aldol reactions as well as no evidence for specific or non-thermal microwave effects. In all cases, in contrast to the previous literature reports, the results obtained with microwave irradiation could be reproduced by conventional heating at the same reaction temperature and time in an oil bath. The differences observed in previous publications could be a result of incorrect temperature measurements [36]. After Kappe s [35] publication several articles appeared in the literature concerning the application of microwaves in asymmetric organocatalysis, mostly in aldol and Michael type reactions operating via enamine as well as iminium catalysis. 

Abstract The organocatalytic asymmetric Mannich reaction and the related aza-Morita-Baylis-Hillman have been reviewed. The activities in this field have been snbdivided based on the types of catalysts that have been ntilized, which includes catalysis by enamine-forming chiral amines, chiral Br0nsted bases, chiral Brpnsted acids, and phase-transfer catalysts. 

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