The Baylis-Hillman Reaction and Its Morita-variant

A solvent-free Baylis-Hillman (BH) reaction using 20 mol% DABCO is very fast and high-yielding, especially for aromatic aldehydes.  

BH reaction of formaldehyde and vinylaldehyde has been studied by DFT in gas phase, with the involvement of one water molecule, and in a bulk-water continuum model 

A review examines design issues involved in producing new organocatalysts to maximize enantioselectivity, and recent advances and mechanistic insights into the asymmetric Morita-Baylis-Hilhnan (MBH) and its aza-variant have been described.  

Rauhut-Currier addition of vinyl sulfones such as l,l-bis(phenylsulfonyl)ethylene to the a-position of a,/3-unsaturated aldehydes is catalysed by NHCs.  

Pendant halogenated o ,/3-unsaturated ketones (77a, R = Ph, n= 1) and esters (77b, R = OEt, = 2) undergo intramolecular MBH-like cycloalkylations timethylphos-phine catalyses C(o ) closure of (77a), whereas NHCs promote C(/3) closure of (77b). A DFT study has examined the reaction mechanisms to probe the reasons for the different closure positions for similar catalysts.  

A review of the Morita-Baylis-Hillman (MBH) reaction has covered mechanism, activated olefins and electrophiles as substrates, multicomponent and intramolecular reactions, and the use of ionic liquid reaction media.  

Kinetic studies have revealed the complex Baylis-Hillman reaction of 3-methoxy-2-nitrobenzaldehyde with CH2=CHCOMe and a second-order dependence on aldehydes for BH reactions in ionic liquids featuring EtS04.  

DFT-based mechanistic studies and free energy computations have explained why enhanced rates of MBH reactions of heterocyclic aldehydes depend on the position of a formyl group.  

Recent advances in organocatalytic asymmetric Morita-Baylis-Hillman reactions and their aza-variants have been reviewed (112 references), with a particular focus on amine- and phosphine-catalysed routes, and bifunctional catalysis. 0 

The catalytic effect of alkylmethylimidazolium ionic liquids as solvents for the Baylis-Hillman reaction has been investigated by DFT, using benzaldehyde, substrate and DABCO as base. 3-Substituted 3-hydroxy-2-oxindoles (76, n = 0, 1) have been prepared in water via an MBH reaction of unprotected isatins with cyclic enones. Bicyclic imidazolyl alcohol (77) is a particularly good catalyst, with its hydroxyl group proposed to stabilize the betaine intermediate. 

A hypervalent silicon complex, generated from silicon tetrachloride and a chiral phosphine oxide, acts as an enantioselective organocatalyst of the MBH reaction, by asym- q. metric delivery of a chloride anion as a nucleophile.  

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The Morita-Baylis-Hillman reaction and its aza-variant - the reaction of an electron-deficient alkene with an aldehyde (MBH) or an imine (aza-MBH) - provide a convenient route to highly functionalized allylic alcohols and amines. This reaction is catalyzed by simple amines or phosphines, which can react as a Michael donor with an electron-deficient alkene, generating an enolate intermediate. This intermediate in turn undergoes the aldol or Mannich reaction with electrophilic C=0 or C=N bonds, respectively, to deliver allylic alcohols and amines. 

Cinchona alkaloid derivatives can also serve as useful Lewis basic catalysts, as very well exemplified by their successful employment in the Morita-Baylis-Hillman (MBH) reaction and its aza variant (aza-MBH), which provide a convenient access to functionalised allylie aleohols and amines. As early as 1999 Hatakeyama and coworkers reported the use of p-isocupreidine (P-ICPD) as a catalyst for the reaction of aliphatic and aromatic aldehydes with 1,1,1,3,3,3-hexafluoroisopropyl acrylate, affording the desired adducts with very high enantioselectivities (Scheme 14.19). The concomitant formation of the dioxanone derivatives lowered the yield in the MBH adducts and caused difficulties in the experimental proeedure. Interestingly, the dioxanone derivatives had the opposite eonfiguration at the alcoholic stereocentre compared to the MBH produet, highlighting an intriguing mechanistic feature of this Lewis-base catalysed reaction. ... 

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