Solvents Morita-Baylis-Hillman reaction

The Morita-Baylis-Hillman reaction can be accelerated by a catalytic amount of lithium bromide and l,8-diazabicyclo[5.4.0]undec-7-ene in a solvent-free medium.171... 

Methylimidazole 3-A-oxide (49) catalyses the Morita-Baylis-Hillman reaction at room temperature under solvent-free conditions addition to the enone reactant to give a zwitterionic enolate (50) is proposed, followed by reaction with aldehyde.177... 

In a different study, based on the reaction rate data collected in aprotic solvents, the Morita-Baylis-Hillman reaction has been found to be second order in aldehyde and first order in DABCO and acrylate. On the basis of these data, a new mechanism has been proposed, involving a hemiacetal intermediate (110). The proposed mechanism is further supported by two different kinetic isotope effect experiments.145... 

A A /V /V -Tetramethylelhylcncdiaminc (TMEDA) as catalyst of the Morita-Baylis-Hillman reaction has been found to be more efficient than DABCO in aqueous media.146 1-Methylimidazole 3-/V-oxide promotes the Morita-Baylis-Hillman reaction of various activated aldehydes with ,/i-unsaturated ketones and esters CH2= CHCOR (R = Me, OMe) in solvent-free systems.147 In another study, the Morita-Baylis-Hillman reaction has been successfully performed under aqueous acidic conditions at pH 1, using a range of substrates and tertiary amines as catalysts.148... 

The addition of electrophilic alkenes to aldehydes in the presence of strong bases occurs under SCCO2 conditions (Morita-Baylis-Hillman reaction (Scheme 29). The reaction proceeds faster in SCCO2 than in organic solvents. At relatively low CO2 pressures ( 80-100 bar), further intermolecular dehydration (dimerization) of the product leads to ethers 18. Unsymmetrical ethers are synthesized using another alcohol in the etherification step. 

Significant rate enhancement of the Morita-Baylis-Hillman reaction through solid-state milling has been noted by Mack et al. (Scheme 2.44). [39], In such conditions, Baylis-HiUman products 130 were obtained in up to >98% yield in as little as 0.5 h by solvent-free reaction of p-nitrobenzaldehyde 129 and methyl acrylate 128. Various bases were tested and l,4-diazabicyclo[2.2.2]octane (DABCO) showed the best performance (Table 2.41). Other p-substimted aromatic aldehydes reacted with methyl acrylate much slower, within 9 5 h and lower yields (28-97%) were obtained. This represents one of the fastest methods of Bayhs-Hilhnan reactions under neat conditions. One of the main drawbacks of this reaction carried out in classical conditions is its slow rate, which has been shown typically to take days to weeks to produce adequate product yields. 

A remarkable rate acceleration of the Morita-Baylis-Hillman reaction of aldehyde ArCHO and activated alkene CH2=CH(EWG), catalysed by 1,4-diazabicyclo[2.2.2]octane (DABCO) (20mol%), has been reported for the solvent-free neat conditions. ... 

The kinetics of the aza-Morita-Baylis-Hillman reaction have been studied for a range of imine substrates in various solvents, using triphenylphosphine as catalyst, and p-nitrophenol as a Brpnsted acid co-catalyst. The effects of varying the phosphineiphenol catalyst ratio on the rate indicate interdependence between them. This and the solvent effects support reversible protonation of zwitterionic intermediates within the mechanism. ip-NMR and quantum calculations also support such a route. 

In the first step, the P-nucleophile adds to the Michael acceptor. The intermediate, bearing a negative charge on the a-carbon atom, then adds to the carbonyl group of the aldehyde. This 3-MCR approach may be an alternative to the Morita-Baylis-Hillman reaction. The interaction of tris(2-p3Tidyl)phosphine with electron-deficient allqmes in water as the solvent led to (J7)-pyridylvinylphosphine oxides in yields of 40-56% (Scheme 2). ... 

Morita-Baylis-Hillman reaction The Morita-Baylis-Hillman (MBH) reaction of aldehydes RCH=0 with the methylene acceptor CH2=CHC02Me, catalysed by DABCO in ionic liquids possessing [EtS04] anion, has been found to exhibit second-order kinetics in aldehyde and first order in acrylate and DABCO. This behaviour is in line with the kinetics reported for DMSO and other aprotic polar solvents but differs from the general observation of the first order in aldehyde, acrylate, and DABCO in other organic solvents. ... 

A series of quinidine-derived organocatalysts, solvents, and temperatures for the asymmetric allylic 5 2 reaction between 0-Boc-protected Morita-Baylis-Hillman adducts and carbamates or tosylcarbamates were tested. The best results were 0 obtained using the catalyst (2) in THF at 20 C. Most of the yields obtained using a variety of substrates were >80%, with >80% ee. 

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