Mannich reaction three component

Related to the Mannich three-component reaction is the Petasis or boronic-Mannich reaction, which involves the reaction between an aldehyde, an amine, and a boronic acid. 

The Mannich reaction is a three component reaction in which an imine, that was formed from the condensation of an amine with an aldehyde, reacts with a component containing at least one hydrogen atom of pronounced reactivity. It is possible to immobilize every Mannich partner on sohd supports. In combinatorial chemistry the Mannich reaction has been used for the generation of different h-braries (Scheme 3.26). 

Allylic amine from the three-component reaction of a vinyl boronic acid, a carbonyl and an amine. Also known as boronic acid-Mannich or Petasis boronic acid-Mannich reaction. Cf. Mannich reaction. 

In parallel to the bismuth(III)-catalyzed three-component allylation reaction, we have reported the corresponding three-component bismuth(III)-catalyzed Mannich-type reaction. A major merit of the three-component reaction is indeed that many unique structures can be afforded rapidly when three or more reactants are combined in a single step to afford new compounds. The development of an efficient bismuth-catalyzed Mannich-type three-component reaction that combines an aldehyde, an amine, and a silyl enolate to give compounds with a (3-amino carbonyl core... 

In origin, the Mannich reaction is a three-component reaction between an eno-lizable CH-acidic carbonyl compound, an amine, and an aldehyde producing / -aminocarbonyl compounds. Such direct Mannich reactions can encompass severe selectivity problems since both the aldehyde and the CH-acidic substrate can often act as either nucleophile or electrophile. Aldol addition and condensation reactions can be additional competing processes. Therefore preformed electrophiles (imines, iminium salts, hydrazones) or nucleophiles (enolates, enamines, enol ethers), or both, are often used, which allows the assignment of a specific role to each car-... 

In another study by Dondoni et al. [17] the synthesis of C-glycosyl-/ -aminoesters as single diastereomers is achieved via a Mannich-type three-component reaction of /Minked C-galactosyl or C-ribosyl formaldehyde, p-methoxybenzyl amine and ketene silyl acetals using catalytic amounts of InCfi (Scheme 9.8). 

The required aldehyde precursor 186 was obtained by a Sn(II)-catalyzed asymmetric aldol reaction [90]. It was then mixed in one pot with o-methoxy aniline 187 and enol ether 188 to afford the key /7-amino ketone 189 in a 2 1 diastereomeric ratio through a Mannich-type three-component reaction. This reaction was performed in an aqueous medium and the use of a surfactant such as dodecyl sulfate (DS) was essential. The diastereomeric mixture 189 was treated with HF and the... 

S)-Proline also catalyzed Mannich reactions of ketone donors in a three-component (donor ketone, 4-methoxyaniline, aryaldehyde) protocol, as shown in Table 2.16 [84b, 90, 91]. In these three component reactions, the C-C bond formation occurred at both a-positions of unsymmetrical alkyl ketones (entry 3), and the ratio of the regioisomers depended on the reactant ketones and aldehydes. When the reaction was performed using a ketone donor possessing an a-hydroxy or methoxy group, C-C bond formation occurred exclusively at the oxy-substituted a-carbon (entries 5-7) the major diastereomer was again the syn-product. The enantioselectivities of (S)-proline-catalyzed three-component... 

Sydnonimines and sydnones can be readily synthesized in a three-component reaction of the Mannich type (Scheme 13) (71CCC2640), for example to prepare 3-lV-hydroxy- (78) or 3-N-amino- (79) substituted sydnonimines (70CPB128, 70JHC123, 71T4449). 

The Hf(OTf)4-catalyzed Mannich-type reaction of imine with enol silyl ethers has been used as a means of access to 8-amino carbonyl compounds (Eq. 21) [23] this also was extended to a three-component reaction (Eq. 22). 

In the solid phase, Sc(OTf)3 also effectively catalyzed Mannich-type three-component reactions of aldehydes, amines, and PSSEEs to afford polymer-supported /3-amino thioesters (Eq. 22). Reductive cleavage from the supports gave the amino alcohols in good to high yields [85b]. /3-Amino acid and /3-lactam libraries are also constructed according by this method (Eq. 23). 

Alder, cyanation, allylation, Michael reaction, and Friedel-Crafts acylation). The same catalyst was also effective in three-component reactions such as Mannich-type reactions, Strecker, and quinoline-forming reactions. The polymer catalyst was recovered and reused many times without loss of activity (Eq. 31). 

The Mannich reaction of a ketone, an amine, and an aldehyde is one of the few three-component reactions in organic chemistry. Cyclohexanone, for example, reacts with dimethyJamine and acetaldehyde to yield an amino ketone ... 

Mannich and Passerini, to whom we owe the two best-known three-component reactions, are the grandparents of the four-component condensation, the Ugi reaction. Its parents are Ugi and Steinbrtick-ner, assisted by coworkers of that period. The godparents are Opitz and Merz, McFarland and Sjoberg. ... 

Aminomethylenation reactions have been carried out, in the presence of a secondary amine, as a three-component reaction <84AP(317)417>. The products are classed as dehydro-A-Mannich bases. 

Mechanistically related to the Mannich reaction is the formation of hydroxyaryl-glycine derivatives in a three-component reaction. ... 

Acyclic chiral a-amino acids or derivatives are also effleient eatalysts for the asymmetric two- or three-components Mannich reaction. Protected or free 2-hydroxyketones reacted with 16 in the presence of L-tiyptophan, O-protected-L-threonine or L-serine and generally led to the a ft-adduct 17, explained by the formation of a (Z)-enamine stabilised by an intramolecular hydrogen bond (Scheme 12.5). Threonine surfactant 14 was equally effective for the three-component reaction with hydro gracetone, benzalde-hyde derivatives and anilines. ... 

Enders et al. also reported direct asymmetric Mannich reactions starting from the protected ketone 14 [10]. Several protected carbohydrates and amino sugars were assembled in a three-component reaction. Alongside L-proline (1) they employed the L-hydroxyproline-based catalyst 17 (Scheme 5.10). This catalyst proved to be beneficial in terms of reaction rate due to superior solubility properties. Remarkably, the addition of water had a positive effect on the stereoselectivity in case catalyst 17 was employed. 

Mannich-type three-component reaction as the key steps (Scheme 30) [290, 291]. 

The Petasis method involves the use of organoboron compounds to produce a side chain on a Mannich product derived from the imine condensation product between an amine and an a-ketocarboxylic acid. Thus, as shown in Scheme 12.64, as an example of this three-component reaction, when the styrylboronic acid derived from the reaction of phenylacetylene with catecholborane was allowed to react with glyoxylic acid (CHOCO2H) and (5)-2-phenylglycinol, a single diastereomer was isolated, which gave an enantiomerically pure (7 )-homophenylalanine hydrochloride on reduction. This procedure is limited only by the availability of the components. 

On the other hand, Zhao s group achieved remarkable results with bifunctional cinchona alkaloid and thiourea catalysts [35], which, over the years, have been broadly employed as catalysts in Mannich reaction. Indeed, as Brpnsted bases, the preferred bifunctional catalyst 46 can lead to the Mannich three-component product 47 with extranely high diastereo- and... 

In the presence of catalytic amounts of Sc(OTf)3 and SDS, three-component Mannich-type reactions of aldehydes, amines, and silyl enol ethers proceeded smoothly in micellar systems to afford the corresponding-amino ketones or esters in high yields (Scheme 3.48). Yb(OTf)3 and Cu(OTf)2 also worked well in this system.Furthermore, three-component reactions of aldehydes, amines, and allyltributylstannane proceeded smoothly in water to afford the corresponding homoallylic amines in high yields (Scheme 3.49). ... 

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