Aqueous Michael reaction

Feringa et al. developed aqueous Michael reactions catalyzed by Yb(OTf)3 (Eq. 1) [4]. fi-keto esters and a-nitro esters could be used as Michael donors for the reaction. a,y3-Unsaturated ketones and a,/5-unsaturated aldehydes without /S-substituents were good Michael acceptors for the reaction but the reaction did not proceed with ethyl acrylate or acrylonitrile. The reported yields were excellent, though the reaction required prolonged reaction time (3-5 days). 

The COj species in the HT interlayer could be exchanged with OH ions by calcination at 723 K and hydration at room temperature. A spinel phase of Mg-Al mixed oxide obtained after the calcination transforms into the original layered structure during the hydration. This reconstruction is known as the memory effect of HT materials. The reconstructed HT catalyzed the Knoevenagel condensation of various aldehydes with nitriles in the presence of water [119]. The reconstracted HT also showed an aqueous Michael reaction of nitriles with a,p-unsaturated compounds. The layered double-hydroxide-supported diisopropylamine catalyzed the Knoevenagel condensation of aromatic carbonyl compounds with malononitrile or ethyl cyanoacetate [120]. This solid base could be recycled at least four times, and exhibited activity for aldol, Henry, Michael, transesterification, and epoxidation of alkenes. 

The extension of this aqueous Michael reaction to acrolein was performed by Deslongchamps. One application was the total synthesis of 13-a -methyl-14a -hydroxys-teroid. 

Acrolein reacts slowly in water to form 3-hydroxypropionaldehyde and then other condensation products from aldol and Michael reactions. Water dissolved in acrolein does not present a hazard. The reaction of acrolein with water is exothermic and the reaction proceeds slowly in dilute aqueous solution. This will be hazardous in a two-phase adiabatic system in which acrolein is suppHed from the upper layer to replenish that consumed in the lower, aqueous, layer. The rate at which these reactions occur will depend on the nature of the impurities in the water, the volume of the water layer, and the rate... 

The Michael reaction of benzylidene acetophenone and benzylidene acetone with ethyl acetoacetate, nitromethane, and acetylacetone was studied by Musaliar and co-workers in the presence of a cetyltrimethy-lammonium bromide-containing aqueous micellar medium.50 The Michael reaction of various nitro alkanes with electrophilic alkenes is performed in NaOH (0.025-0.1 M) in the presence of cetyltrimethylam-monium chloride (CTACI) without any organic solvent (Eq. 10.23).51... 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

Quantitative studies of Michael-type additions in aqueous solutions are relatively scarce. Recently the rate-determining steps of the Michael reaction were investigated with substituted pyridines as nucleophiles (Heo and Bunting, 1992). The uncatalyzed Michael reaction proceeds nicely under neutral conditions when water is used as solvent, without any catalyst. 

Conjugate additions of carbamates to a, P-unsaturated enones require - apart from metal halide - TMSC1 as a stoichiometric additive [96]. The addition of ethyl carbamate to cyclohexenone (41h) requires only 50mol% TMSC1, which was an exceptionally low amount compared with other Michael acceptors. With 10 mol% of the catalyst, the yield of 3-aminocyclohexenone derivative 66 was good (93%) [97], Aza-Michael reactions also proceed in aqueous media with good results if Co(II),... 

Scheme 8.30 Aza-Michael reactions of carbamates in aqueous media.

Dihydropyridine 129 has been shown to catalyze Michael reactions in aqueous cationic micelles of cetyltri-methylammonium bromide (Scheme 34) <2003CL1064>. In the micelles, dihydropyridine 129 ionizes to form an acetophenone enolate salt 130. The highly basic enolate deprotonates the Michael donor which then rapidly reacts with the Michael acceptor. The use of anionic surfactants did not promote Michael reactions, suggesting that the cationic micelles promote the dissociation of salt 130. 

Roelfes s supramolecular assembly is one of the most efficient enan-tioselective catalysts for aqueous Michael additions. The DNA template approach has also been used for enantioselective Friedel-Crafts reactions in water, with outstanding results in terms of conversion and enantioselectivities (110). All these results confirm the impressive potential of DNA-based enantioselective catalysis. 

When the product of a Michael reaction is also a p-keto ester, it can be hydrolyzed and decar-boxylated by heating in aqueous acid, as discussed in Section 23.9. This forms a 1,5-dicarbonyl compound. Figure 24.7 shows a Michael reaction that was a key step in the synthesis of estrone, a female sex hormone. 

With optimized process operation the reaction is strongly regioselective. The process is commercialized by Rhone-Poulenc using Ruhrchemie s TPPTS and yields precursors for vitamin E cf. Section 3.1.1.1.3 [163, 164] Sc or Y triflates catalyze aqueous biphasic reactions which are alternatives to base-catalyzed processes such as aldol or Michael-type conversions [257]. 

Michael reactions. The addition of amines to chalcones can be accomplished in aqueous suspensions of the reactants in the presence of cetyltrimethylammonium halides, i.e., organic solvents are not required. 

General comments about the Michael reaction procedures are analogous to those developed in the aldol and Mannich reactions.For example, the O-TMS-protected diphenylprolinol compound 20 in cooperation with benzoic acid catalyses the asymmetric Michael addition of aldehydes to nitroalkenes, in a simple, practical and efficient procedure. Benzoic acid promotes the rapid formation of the enamine intermediate and the reaction takes place in the highly concentrated organic phase of the aqueous biphasic system. 

With chiral diamine 24, in the form of a trifluoroacetate salt, the classic aqueous biphasic protocol has been successfully applied to the asymmetric Michael reaction of ketones with both aryl and alkyl nitroolefins. Brine is used as the aqueous phase. ... 

Noteworthy was the increase of the selectivity in water toward the 1 1 adduct when using nitromethane. Under slightly alkaline conditions, cetyltrimethylam-monium chloride was shown to catalyze the addition of various nitroalkanes onto conjugated enones [176]. Amines also reacted in aqueous Michael additions, especially with a, -unsaturated nitriles [177]. The lack of apparent reactivity of a, -unsaturated esters comes from the reverse reaction which is particularly accelerated in water. In these amine additions, water activation was compared with high pressure giving support to the implication of the hydrophobic effect. A related reaction is the Baylis-Hillman reaction which proceeds readily in water with a good rate enhancement (Scheme 34) [178]. 

A huge acceleration of the Michael reaction of nitroalkanes with methyl vinyl ketone was mentioned when going from non-polar organic solvents to water. The hydrophobic effect could be at least to some extent involved, since additives, such as glucose or saccharose, accelerate the reaction even more [72]. Cetyltrimethylam-monium chloride as an amphiphilic species which can influence the hydrophobic interactions was found to promote the Michael reaction of various nitroalkanes with conjugated enones in dilute aqueous solutions of sodium hydroxide [73],... 

Numerous organic reactions have been studied in aqueous solutions. It was observed that water is able to induce dramatic rate accelerations in Diels-Alder cycloadditions [66], benzoin condensation [67], Claisen rearrangements [68], Mu-kaiyama aldol reactions [57], Michael reactions [69], Baylis-Hillman reactions [70], and 1,3-dipolar cycloadditions [71], All these reactions are characterized by negative volume changes and negative volumes of activation. It is expected that ground state destabilization in aqueous media associated with transition state stabilization is one of the determining kinetic factors. 

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