Synthesis, characterization and catalytic properties of chiral BINOL functionalized mesoporous silicas for enantioselective Morita-Baylis-Hillman reaction

Several Chiral BINOL functionalized mesoporous silicas were prepared by post grafting of organosilane derivatives of (S)-BINOL (1,1'-bi-2-naphthol) on SBA-15 and characterized by C-13 CP/MAS NMR, FT-IR, UV-visible absorption spectra, elemental analysis, powder XRD, nitrogen adsorption-desorption isotherms and TEM techniques. Their catalytic properties were demonstrated in enantioselective Morita-Baylis-Hillman reaction of 3-phenylpropanal and cyclohexenone.

Rate acceleration of the Baylis-Hillman reaction in polar solvents (water and formamide). Dominant role of hydrogen bonding, not hydrophobic effects, is implicated

A substantial acceleration of the Baylis-Hillman reaction between cyclohexenone and benzaldehyde has been observed when the reaction is conducted in water. Several different amine catalysts were tested, and as with reactions conducted in the absence of solvent, 3-hydroxyquinuclidine was found to be the optimum catalyst in terms of rate. The reaction has been extended to other aldehyde electrophiles including pivaldehyde. Attempts to extend this work to acrylates was only partially successful as rapid hydrolysis of methyl and ethyl acrylates occurred under the base-catalyzed and water-promoted conditions. However, tert-butyl acrylates were sufficiently stable to couple with relatively reactive electrophiles. Further studies on the use of polar solvents revealed that formamide also provided significant acceleration and the use of 5 equiv of formamide (optimum amount) gave faster rates than reactions conducted in water. Using formamide, further acceleration was achieved in the presence of Yb(OTf)(3) (5 mol %). The scope of the new conditions was tested with a range of Michael acceptors and benzaldehyde and with a range of electrophiles and ethyl acrylate. The origin of the rate acceleration is discussed.

Bronsted Acid Catalyzed Morita-Baylis-Hillman Reaction: A New Mechanistic View for Thioureas Revealed by ESI-MS(/MS) Monitoring and DFT Calculations

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

A synthesis of captopril through a Baylis-Hillman reaction

A synthesis of the antihipertensive amide 1, named captopril, is described. The strategy is based on a Baylis-Hillman reaction between N-acryloylproline and formaldehyde. Subsequential diastereoselective hydrogenation step and functional group interconversion provided captopril in good overall yield.

Highly Substituted Isoxazoles: The Baylis-Hillman reaction of substituted 4-isoxazolecarbaldehydes and attempted cyclization to isoxazole-annulated derivatives

In an attempt to understand the effect of position of the formyl group on the efficiency of Baylis-Hillman reaction within isoxazolecarboxaldehydes, the reactions of substituted 4-isoxazolecarboxaldehydes to obtain highly substituted isoxazoles are described. Attempts to obtain isoxazole-annealed derivatives from these Baylis-Hillman adducts involving SNR’-SNAr substitu-tion strategy are also described.

Facile Baylis-Hillman reaction of substituted 3-isoxazolecarbaldehydes: The impact of proximal heteroatom within a heterocycle on the acceleration of reaction

The fast and facile Baylis-Hillman reaction in substi-tuted 3-isoxazolecarbaldehydes confirms the impact of the proxi-mal heteroatom within a heterocycle towards enhanced reactivity of the formyl group for this reaction

Studies on the Baylis-Hillman reaction of pyrazolecarbaldehydes under the influence of DABCO: Positional effect on the reactivity of the formyl group

Results of the study to assess the difference in reactivity of the formyl group present at various positions in substituted pyrazolecarbaldehydes for the Baylis-Hillman reaction under the influence of DABCO are described.

Baylis-Hillman reaction assisted parallel synthesis of 3, 5-disubstituted isoxazoles and their in vivo bioevaluation as antithrombotic agents

The solution phase parallel synthesis involving reactions of Baylis-Hillman products of 3-substituted-5-isoxazolecarbaldehydes with nucleophiles and their in vivo antithrombotic evaluations are described along with the results of in vitro platelet aggregation inhibition assay of a few compounds. Results of the detailed evaluation of one of the compounds as an inhibitor of platelet aggregation are also presented.

Baylis-Hillman reaction assisted synthesis of substituted 5,8-dihydro-isoxazolo[4,5-c]azepin-4-one: A novel isoxazole-annulated heterocycle

The novel synthesis of a new isoxazole-annulated heterocycle namely 5,8-dihydro-isoxazolo[4,5-c]azepin-4-one described herein is based on the reaction of benzyl amine with acetates of Baylis-Hillman adducts generated from 3-aryl-5-formyl-isoxazole-4-carboxylate

Evaluating the Baylis-Hillman reaction of cyclic enones using surfactants in water

Conjugated cyclic enones react smoothly in water with a variety of aldehydes (Baylis-Hillman reaction) in the presence of surfactants above their critical micelle concentrations (CMC).

Metallic chalcogenolates mediated modular Michael-aldol cascade reaction: an easy route to multi-functionalized chalcogenides and Morita-Baylis-Hillman adducts

Chalcogenolate mediated Michael-aldol cascade reactions consists of a very efficient route to multi-functionalized gamma-hydroxichalcogenides. Although, when selenolates are employed, these gamma-hydroxichalcogenides can be readily converted into the corresponding Morita-Baylis-Hillman adducts by oxidative elimination of the selenium moiety. In this context, herein we present a complete study on the scope and limitations of this reaction. (C) 2012 Elsevier Ltd. All rights reserved.

A Facile, Versatile, and Mild Morita-Baylis-Hillman-Type Reaction for the Modular One-Pot Synthesis of Highly Functionalized MBH Adducts

MoritaBaylisHillman derivatives have been extensively investigated as intermediates in the preparation of important classes of compounds. However, there are intrinsic limitations regarding the structure of the Michael electrophile acceptors, the aldehydes, and the catalysts. Therefore, this transformation has several drawbacks, including, for example, its long reaction times. Herein we present a simple, general, fast, and high-yielding protocol for the one-pot synthesis of MoritaBaylisHillman derivatives. Our approach is driven by a lithium selenolate Michael/aldol operation with concomitant O-functionalization/selenoxide elimination cascade sequences.

Sodium hydride-mediated cascade reaction towards the synthesis of 1,5-disubstituted uracil from cyanamides derived from the Baylis-Hillman ad-ducts

Sodium hydride-mediated cascade reaction towards the synthesis of 1,5-disubstituted uracil from cyanamides derived from the Baylis-Hillman ad-ducts

An alternate approach to quinoline architecture via Baylis-Hillman chemistry: SnCl2-mediated tandem reaction toward synthesis of 4-(substituted vinyl)-quinolines

An alternate approach to densely substituted quinolines from the products of SN2 nucleophilic substitution reaction between the acetyl derivatives of the Baylis-Hillman adducts obtained from 2-nitrobenzaldehydes and the carbonyl group containing carbon nucleophiles is described. Treatment of these compounds with SnCl2, trigger a tandem reaction wherein reduction of the nitro group is followed by a remarkably regioselective intramolecular cyclization and subsequent dehydrogenation to afford 4-(substituted vinyl)-quinolines.

Trifluoroacetic acid: A more effective and efficient reagent for the synthesis of 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones and 3-arylmethyl-2-amino quinolines from Baylis-Hillman derivatives via Claisen rearrangement

Trifluoroacetic acid has been discovered to be a highly effective and efficient reagent for the tandem Claisen rearrangement and cyclisation reaction to yield 3-arylmethylene-3,4-dihydro-1H-quinolin-2-ones from compounds obtained from the SN2 reaction between anilines and acetyl derivatives of Baylis-Hillman adducts of acrylates in the presence of DABCO. In contrast similar compounds obtained from the acetyl derivatives of Baylis-Hillman adduct of acrylonitrile on treatment with trifluoroacetic acid directly furnish 3-arylmethyl-2-amino-quinoline via tandem Claisen rearrangement, cylisation and isomerisation.