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Baylis Hillman Reaction

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Functionalized allyl alcohols are important synthetic intermediates in multi step organic transformations and new methods for their preparation have always attached the attention of organic chemists.

The Bayllis-Hillman reaction provides ready access to such alcohols. This reaction of vinylic esters ketones and nitriles with aldehydes in the presence of catalytic amounts of a trialkylamine, for example, DABCO $\alpha$-metthylene-$beta$-hydroxy moieties.

However the BH reaction has several drawbacks such as slow reaction rate and lack of reactivity with ketones. The lack of reactivity with $\beta$-substituted vinyilic substrates also limits the scope of this reaction. Due to the polymerization of fluorocarbonyls in the presence of amines, BH reactions of perfluoroaldees and ketones are difficult.

Baylis Hillman Reaction

Mechanism

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The commonly accepted mechanism for the Baylis-Himann reaction which was subsequently refined by others. The reaction involves first a reversible Micheal addition of the nucleophilic catalyst onto the activated alkene to produce an enolate followed by an aldolic reaction to aldehyde or imine to result in zwitterionic intermediate. An intramolecuar proton transfer to form intermediate and an E1 and E2 elimination to generate the product while the catalyst is released to complete the cycle. This mechanism was based on pressure dependence, rate and kinetic isotope effect. The aldolic reaction is the rate determining step.

Baylis Hillman Reaction Mechanism

Asymmetric Morita Baylis Hillman Reaction

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In 1992 Frater and cowworkers documented the first asymmetric intramolecular reaction utilizing P-chiral phosphine catalyst in the cyclization of enolate ketone to cyclopentanol in 40 % yield. First phosphine catalyzed asymmetric intramolecular MBH reaction is shown below.

Asymmetric Morita Baylis Hillman Reaction
Recognizing the daunting challenge of preparing optically pure P-chiral phosphines, Soai disclosed the first asymmetric intermolecular MBH reaction in 1998.

Applications

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The Baylis-Hillman reaction is an atom economical reaction but days or weeks have been required but days or weeks have been made to accelerate it. Recently a recyclable protic ionic liquid solvent catalyst system has been developed and used in the Baylis-Hillman reaction or aromatic aldehydes and cinnamaldehydes with acrylates and acrylonitrile. Comparable performance to free DABCO in traditional solvents was observed.

One of the tools used to combine economic aspects with the environmental ones is the multi component reaction strategy. Recently the use of MCR for the synthesis of 2-amino-2-chromones using the basic ionic liquid catalyst N,N-dimethyl amino ethyl benzylammonium chloride was described as an efficient catalyst under solvent free conditions.