Ionic liquids Mannich reaction

In addition to the ionic liquid-mediated procedure in solution (see Scheme 6.112), Leadbeater and coworkers also presented a solid-phase protocol for a one-pot Mannich reaction employing the above mentioned chlorotrityl linker [67]. In this approach, p-chlorobenzaldehyde and phenylacetylene were condensed with readily prepared immobilized piperazines (Scheme 7.56). 

Figure 15. Mannich reaction catalysed by the acidic ionic liquid 16 under solvent-free conditions.

Li and coworkers reported their primary results on the Mannich reaction catalyzed by a cation-functionalized acidic ionic liquid, l-carboxymethyl-3-methylimidazo-lium tehafluoroborate ([cmmim][BF ]) in the mixture of water and l-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF ]) (Fig. 12.6) [5]. 3-aminoketone derivatives were synthesized successfully in aqueous [bmim][BF ] with satisfactory to excellent yields, and the catalyst-containing aqueous media can be recycled at least six times with similar activity. In their procedure, the recovered catalyst-containing aqueous media could be reused directly (straightforwardly) without other manipulation such as distillation and dehydration. 

Dong et al. reported the preparation of a novel Brbnsted acid-surfactant-combined halogen-free ionic liquid [DDPA][HSO ] that bears a propane sulfonic acid group in an acyclic dimethyldodecylammonium cation (Fig. 12.69) [42] and its use in the heterogeneous catalysis procedure of one-pot three-component Mannich-type reaction in aqueous media. 

Li J, Peng Y, Song G (2005) Mannich reaction catalyzed by carboxyl-functionalized ionic liquid in aqueous media. Catal Lett 102 159-162... 

Gong K, Dong F, Wang HL, Liu ZL (2007) Basic functionalized ionic liquid catalyzed one-pot Mannich-type reaction three component synthesis of P-amino carbonyl compounds. Monatsh fur Chemie 138 1195-1198... 

Zheng X, Qian YB, Wang Y (2010) 2-Pytrotidinecarboxyhc add ionic liquid as a highly efficient organocatalyst for the asymmetric one-pot Mannich reaction. Eur J Org Chem 515-522... 

Dong F, Zhenghao F, Zuliang L (2009) Functionalized ionic liquid as the recyclable catalyst for Mannich-type reaction in aqueous media. Catal Commun 10 1267-1270... 

The Mannich reaction involves the condensation of an aldehyde or ketone with an iminium salt usually derived from formaldehyde or other aldehyde and an amine. An example is the use of four acidic ionic liquids in the reaction of benzaldehyde, aniline and acetophenone to give a /S-amino ketone as in Scheme 5.2-114 [259]. 

A Mannich type reaction was used in the three-component synthesis of isoquino-lic acids in [BMIM][BF4] or [BMIM][PF6] [260] (Scheme 5.2-115). These reactions are normally catalyzed by Lewis acids such as BF3-OEt2, TiQ4 or SnCU. The reaction in the ionic liquids does not require a catalyst to be added, although addition of 5 mol% of indium(iii) chloride does marginally improve the yield (87-95%). 

Scheme 5.2-114 The Mannich reaction in acidic ionic liquids [259].

L-proline-derived sulfonamides 15b and 15c are also effective catalysts in the Mannich reaction of cyclic ketones with N-PMP-protected cx-imino ethylglyoxylate in both classical organic solvents and ionic liquids as the reaction media. ... 

In 2003, the groups headed by Hayashi [80], Barbas [81], and Cordova [82] simultaneously extended the scope of this asymmetric MCR using aldehyde donors in the presence of chiral pyrrolidine-based catalysts for the so-called enantioselective cross-Mannich reaction (Scheme 16.39). This efficient combination of two different aldehydes has led to a highly stereoselective synthesis of 3-amino aldehydes and y-amino alcohols. Recently, chiral ionic liquids have been efficiently used as catalysts for similar asymmetric Mannich reactions [83]. 

Polynitroalkanes undergo Henry and Mannich reactions in ionic liquids. TMS-methylenenitronate (75) reacts with aliphatic and aromatic aldehydes to give Henry reaction products, with scandium(III) triflate as catalyst. ... 

RasaUcar, M.S., Bhilare, S.V., Deorukhkar, A.R., Darvatkar, N.B., Salunkhe, M.M. 2007. Heteropoly acid in ionic liquid—An efficient and recyelable system for one-pot three-component Mannich reaction. Canadian Journal of Chemistry Revue Canadienne De Chimie 85(l) 77-80. 

Moreover, Teo s group worked on the development and application of siloxy serine organocatalysts [30]. Particularly, when (S)-37 was used, the reaction could be performed in water with a consequent low environmental impact (Scheme 2.10a), and the onli-Mannich products 38 were isolated in interesting ee (np to 90%). Pursuing this research, in 2011, the same group has highlighted the remarkable properties of ionic liquids 39 as solvents (Scheme 2.10b, up to 99% ee) [31]. The developed strategy ensured the recyclability of the catalyst (S)-37 in Mannich reaction after three cycles, they obtained an identical stereoselectivity and reactivity as well as the ionic liquid preserved its biphasic properties, whereas the next three cycles displayed a decrease in ee and yield. 

Comparably, Barbas HI et al. observed interesting results employing the quite similar ionic liquid 40 as solvent in a proline-catalyzed Mannich reaction (Scheme 2.11a, up to 95% ee) [32], whereas, Wang s group examined the properties of more complex ionic liquids as enamine activation catalysts (Scheme 2.1 lb). The best outcome in terms of yield (up to 99%) and stereoselectivities (91-99% ee) was observed performing the reaction in DMF at -20 °C and using 30 mol% of[EMlm][Pro] 41 [33]. 

F.-F. Yong, Y.-C. Teo, Synth. Commun. 2011, 41, 1293-1300. Recyclable sUoxy serine organocatalyst for the direct asymmetric Mannich reactions in ionic liquids. 

N. S. Chowdari, D. B. Ramachary, C. F. Barbas, III, Synlett 2003, 1906-1909. Organocatalysis in ionic liquids highly efficient L-prohne-catalyzed direct asymmetric Mannich reactions involving ketone and aldehyde nucleophiles. 

Ionic liquids [61], were found to accelerate the Petasis boron Mannich reaction of 2-hydroxy aryl aldehydes, secondary amines, and arylboronic acids, under mild conditions, by the group of Yadav [62]. As far as we are aware, these authors were the first (and only ) to report the use of ionic liquids in this reaction. The remarkable features of this procedure were the improvement of yields in the synthesis of the desired products, as well as enhanced reaction rates and the possibility of recycling the ionic liquid for up to five times without apparent loss in enantioselectivity. 

Phosphazenes has also been used as catalysts in several other reactions including asymmetric Mannich reaction,ring-opening polymerization of rac-lactide and cyclic esters as well as in the oxidation of anthrones. Luminescence of room temperature ionic liquids containing triallyl-(pentafluorocyclotriphosphazenyl)ammonium moieties (180) was studied. They all revealed blue-luminescence under an excitation of... 

In 2005, Cordova and coworkers described the first example of the enantioselective organocatalytic aza-hetero-Diels-Alder reaction [60]. The one-pot three-component direct aza-hetero-Diels-Alder reaction under the catalysis of prohne afforded the desired cycloadducts 135 with excellent chemo-, regjo-, and stereoselectivity (Scheme 38.39). This reaction was considered to proceed via a plausible Mannich-Michael reaction pathway. Recently, Wang and coworkers developed a chiral ionic liquid catalyst for this reaction to afford up to >99% ee [61]. 

Lessard and Li applied the cation pool method to the nitro-Mannich reaction of N-phenyl THIQ with nitromethane which is well known to proceed in the presence of various oxidants (Scheme 8.57). The reaction is effectively promoted in the ionic liquid [BMIm][BF4] to afford 114 in good yield. 

Scheme 8.57 Nitro-Mannich reaction by the cation pool method in an ionic liquid.

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