Baylis Hillman Reaction Research Articles

Baylis–Hillman reaction based flexible strategy for the synthesis of gabosine I, gabosine G, epi-gabosine I and carba l-pentose

A combination of diastereoselective Baylis–Hillman reaction and RCM reaction set is used as the flexible strategy for the ready access to cyclohexenoid and cyclopentenoid skeletons.

First Stereoselective Total Synthesis of Isoaspinonene through a Baylis–Hillman/Olefin Cross‐Metathesis Protocol

AbstractThe first stereoselective and efficient total synthesis of isoaspinonene by using Baylis–Hillman reaction, chelation‐controlled vinyl Grignard reaction, Wittig olefination, and olefin cross‐metathesis reaction of a hitherto unreported substrate as the key steps is described.

ChemInform Abstract: A Bifunctional Spiro‐Type Organocatalyst with Enantiocontrol: Application to the Aza‐Morita—Baylis—Hillman Reactions.

ChemInform Abstract: A Bifunctional Spiro‐Type Organocatalyst with Enantiocontrol: Application to the Aza‐Morita—Baylis—Hillman Reactions.

Exploring the Scope of the Baylis–Hillman Reaction for the Synthesis of Side‐Chain Functional Polyesters

AbstractThe Baylis–Hillman reaction provides a protective‐group‐free strategy to heterobifunctional polyesters, which can be further modified via various post‐polymerization modification reactions. This contribution explores the Baylis–Hillman polymerization of 1,3‐butanediol diacrylate with two readily available dialdehyde monomers, iso‐ and terephthaldehyde. The influence of a variety of catalysts and additives on the polymerization of these two pairs of monomers and in particular the molecular weight of the resulting polymers was investigated. The presence of the orthogonally reactive vinyl and hydroxyl groups makes the polymers interesting, e.g., as precursors for dual‐cure coatings.

ChemInform Abstract: Catalytic Asymmetric Baylis—Hillman Reactions and Surroundings

AbstractReview: 150 refs.

Total synthesis of (+)-pericosine B and (+)-pericosine C and their enantiomers by using the Baylis–Hillman reaction and ring-closing metathesis as key steps

A simple and divergent route for the total synthesis of pericosine B and pericosine C and their enantiomers from d-ribose by using the Baylis–Hillman reaction and ring-closing metathesis reactions as key steps has been described.

Synthesis of novel-9-cyano/acetylpyrano[2,3-f]chromones via Baylis-Hillman reaction

Abstract Condensation of 8-formyl-7-hydroxy chromones 2a–e with methyl vinyl ketone and acrylonitrile in the presence of diazabicyclo[2.2.2]octane (DABCO) under Baylis-Hillman reaction conditions afforded 9-cyano/acetyl-substituted pyrano[2,3-f]chromones 3a–e and 4a–e.

ChemInform Abstract: Chiral Amines Derived from Asymmetric Aza‐Morita—Baylis—Hillman Reaction

AbstractReview: 90 refs.

Asymmetric Morita–Baylis–Hillman reactions of 2-cyclohexen-1-one catalyzed by chiral biaryl-based bis(thiourea) organocatalysts

Newly-developed bis(thiourea) 1d was found to be an efficient organocatalyst for the Morita–Baylis–Hillman reaction. High enantioselectivities were obtained in the reaction of 2-cyclohexen-1-one with both aromatic aldehydes (up to 84% ee) and aliphatic aldehydes (up to 96% ee).

The intramolecular Morita–Baylis–Hillman-type alkylation reaction

From the initial development of a homologous Morita–Baylis–Hillman reaction utilizing epoxides as electrophiles, the method was expanded to enable the exclusively organocatalyzed intramolecular allylation of enones and to develop the intramolecular MBH-type alkylation of activated alkenes. We successfully utilized both enones and unsaturated thioesters as the activated alkene component. This work, carried out using stoichiometric amounts of the trialkylphosphine, gave an array of functionalized five- and six-membered carbocycles in high yields. With the cycloalkylation of enones and thioesters, conditions that allowed the use of substoichometric amounts of the phosphine catalyst were developed. As a result both five- and six-membered rings can be formed efficiently with little to no loss in yield upon comparison to yields obtained when stoichiometric amounts of trialkylphosphines were employed. We isolated, for the first time, an MBH-type intermediate exhibiting unprecedented trans geometry of the phosphonium salt and acyl group.

L-proline and l-histidine co-catalyzed Baylis–Hillman reaction

Baylis–Hillman reaction between an aldehyde and an activated alkene, such as alkyl vinyl ketones, acrylates, acrylonitrile, and vinylsulfones, giving the β-hydroxy-α-methylene carbonyl compounds, is a versatile and atom-economical carbon–carbon bond-forming reaction. This reaction usually is catalyzed by strong Lewis bases such as tertiary amines and suffers from slow reaction rate. In this paper the Baylis–Hillman reaction between arylaldehydes and methyl vinyl ketone was successfully realized by a catalytic amount of l-proline and l-histidine system to give the corresponding normal Baylis–Hillman adducts in moderate to high yields for the first time. The effects of solvent and reagent electro property on the yields of this reaction were also investigated. Proline and histidine are naturally widely present amino acids in food system; furthermore, aldehydes and activated alkenes can also be easily produced in food processing, so proline and histidine co-catalyzed Baylis–Hillman reaction may find application in explaining some phenomena in food processing.

Convenient Synthesis of 3-Methylcoumarins and Coumarin-3-carbaldehydes

Rapid, microwave-assisted Baylis–Hillman reactions of substituted salicylaldehydes, followed by one-pot hydrogen iodide–mediated cyclization and reduction of the corresponding adducts, has afforded 3-methylcoumarins in up to 94% yield in the final step. Subsequent microwave-assisted selenium dioxide oxidation of selected 3-methylcoumarins has provided convenient access to the corresponding coumarin-3-carbaldehydes and permitted a significant improvement over the yield obtained using conventional heating.

Switching the Reactivity of Dihydrothiopyran-4-one with Aldehydes by Aqueous Organocatalysis: Baylis–Hillman, Aldol, or Aldol Condensation Reactions

An aqueous medium containing catalytic amounts of a tertiary amine was employed to direct the chemoselectivity of the reaction of aldehydes with 1a. With DBU, 2 was formed at room temperature as a rare exemplary of Baylis-Hillman reactions in heterocyclic enones. DABCO alternated the pathway toward an aldol reaction to form syn/anti mixtures of 3 with the syn isomers being the major products. With Et(3)N, aldol condensation dominated.

Antibacterial Potential of Citral Derivatives

Nine conjugated acid derivatives from monoterpene citral have been synthesized using ester, amide condensations, Wittig, Knoevenagel, Baylis-Hillman reactions and their antimicrobial activities were evaluated through disc diffusion and serial dilution methods. Several derivatives displayed interesting antimicrobial activity. Particularly, the Baylis-Hillman adducts 8-10 were found to have more potent antibacterial and antifungal activities than standard drugs namely chloramphenicol and nystatin respectively.

Enantiopure trans-1-amino-2-(arylsulfanyl)cyclohexanes: novel chiral motifs for ligands and organocatalysts

In order to obtain the title compounds (1 R,2 R)-cyclohexane-1,2-diol was stereoselectively converted into cis-(1 R,2 S)-2-(arylsulfanyl)cyclohexanols and these products were submitted to the nucleophilic substitution via the Mitsunobu reaction (HN 3, DEAD). Reduction of the isolated azides gave the desired trans-(1 S,2 S)-1-amino-2-(arylsulfanyl)cyclohexanes. The (1 S,2 S)-1-amino-2-(2-aminophenylsulfanyl)cyclohexanes thus prepared were reacted with 3,5-bis(trifluoromethyl)phenyl isothiocyanate to furnish the respective bis-thiourea compounds. An application of a derivative of this type as an organocatalyst (20 mol %) in the Baylis–Hillman reaction gave the respective product in up to 93% ee.

Facile One-Pot Synthesis of Inden-1-ol Derivatives

Abstract: A facile one-pot synthesis of a novel class of inden-1-ol/indanone derivatives has been developed and formation of ionicclusters by lithium perchlorate has been demonstrated using UV-visstudies. Key words: methyl ketones, o -phthaldialdehyde, inden-1-ol deriv-atives, b-anomer, XRD analysis Carbon–carbon bond formation remains an importantchallenge for synthetic organic chemists. 1,2 Among differ-ent C–C bond-formation reactions the Morita–Baylis–Hillman reaction (MBH) 3–5 has received growing interestsince the mid 1990’s as it converts simple starting materi-als, in the presence of a catalyst such as trialkylphos-phine, 6 pipecolic acid, N -methylimidazole, 7 ortriphenylphosphine 8 into highly functionalized com-pounds, which can be used for further transformations. 4 Inaddition, intramolecular BH ring-closing reactions offeradditional opportunities in synthetic design. 9 In one in-stance, the substrates for cyclization were prepared by ox-idative cleavage of vicinal cyclohexenediols

Stereoselective synthesis of functionalized pyroglutamates

Novel stereoselective synthesis of α-methylene-β-substituted pyroglutamates, and α-alkylidene-pyroglutamates has been achieved via substrate controlled asymmetric alkylation of l-threonine derived oxazole with Baylis–Hillman reaction based allyl bromides and acetates, respectively. The synthesized compounds were evaluated for their proteasome inhibition and cytotoxicity on multiple myeloma cells.

Synthesis of Novel Poly(ethyleneglycol)-400 Ionic Liquid and Its Application in Morita–Baylis–Hillman Reaction

Novel Poly(ethyleneglycol)-400 ionic liquid containing imidazolium cations have been synthesized by the atom-efficient reaction of 1,2-dimethylimidazole with p-toluenesulfonate; the p-toluenesulfonate provides the anionic component of the resultant ionic liquid. It have been used for the first time as a new solvent for the Morita–Baylis–Hillman reaction under ambient conditions. A wide variety of aldehydes and active olefins participate very efficiently, resulting in good to excellent yields of products.

Synthesis, evaluation against Leishmania amazonensis and cytotoxicity assays in macrophages of sixteen new congeners Morita–Baylis–Hillman adducts

We report the design, synthesis, in vitro evaluation against Leishmania amazonensis (IC 50), cytotoxicity assays in macrophages (CC 50), and selectivity index (SI CC 50/IC 50) of sixteen new congeners aromatic Morita–Baylis–Hillman adducts 1– 16. The 1– 16 were prepared in good to excellent yields (58%–97%) from the “one pot” Morita–Baylis–Hillman Reaction between the aldehydes 29– 36 and the acrylates 27 or 28 under DABCO as promoter. The MBHA 2-[Hydroxy(2-nitrophenyl)propyl] propanoate ( 1, IC 50 = 7.52 μg/mL or 28.38 μM; CC 50 = 35.77 μg/mL or 134.98 μM; SI = 4.75) and 2-[Hydroxy(2-nitrophenyl)hydroxyethyl] propanoate ( 9, IC 50 = 5.48 μg/mL or 20.52 μM; CC 50 = 29.81 μg/mL or 111.64c μM and, SI = 5.43) were the most effective and safe evaluated compounds.

ChemInform Abstract: An Efficient and Simple Morita—Baylis—Hillman Reaction Based on the N‐Methylpyrrolidine—Ba(OH)2 Catalytic System.

AbstractMorita—Baylis—Hillman reaction of cyclic enones with formaldehyde or simple aromatic and aliphatic aldehydes is efficiently catalyzed by a NMP/Ba(OH)2 catalyst combination.