Horner-Emmons Reaction Research Articles

Interaction of the Fluorophenyl Analog of Retinal with Proteorhodopsin from Exiguobacterium sibiricum

—We have developed an alternative method for the synthesis of an analog of natural retinal, which contains the p-fluorophenyl fragment instead of the trimethylcyclohexene ring. The proposed scheme for the synthesis of the target all-E-isomer of the target retinoid consists of using C5-phosphonate that contains the terminal nitrile group under Horner–Emmons reaction conditions. It has been shown that this scheme is more efficient and provides a higher total yield of the target product than the previously described variant. The procedure has been developed for the preparation of an analog of microbial proteorhodopsin ESRh from Exiguobacterium sibiricum, which contains a modified chromophore. It has been found that, as in the case of bacterioopsin from Halobacterium salinarum, the replacement of the trimethylcyclohexene ring in the natural chromophore by the p-fluorophenyl fragment does not prevent the formation of the artificial pigment F-Phe-ESRh from proteorhodopsin ESRh, which preserves the cycle of photochemical reactions. Certain differences have been found between the properties of native recombinant ESRh and its analog F-Phe-ESRh including a shift in the absorption maximum to the short-wavelength region, the formation of M intermediate at lower pH values, the presence of “long-lived M,” and a general slowdown in the photocycle. The reduced stability of the resulting proteorhodopsin analog F-Phe-ESRh to prolonged exposure to visible light has been also demonstrated.

Efficient Synthesis of New 2H‐Chromene Retinoids Hybrid Derivatives by Suzuki Cross‐coupling Reactions

In an attempt to improve anticancer activity, a series of retinoids–chromene hybrids was described. The novel heterocyclic chromene–retinoids hybrid including oxygen as a heteroatom in a six‐membered cyclic ring (2H‐chromene or 2H‐1‐benzopyran) was designed and synthesized by introducing different groups such as an aromatic or styrylphenyl ring in 6‐position of 2H‐chromene. These novel compounds were synthesized by using the efficient cascades one‐pot process involving Wittig–Horner–Emmons reaction and Suzuki–Miyaura cross‐coupling pallado‐catalyzed reactions with 60% to 90% overall yields. These new compounds were tested against glioblastoma multiforme brain cancer, medulloblastoma, neuroblastoma cell lines, and breast cancer MCF‐7 cell lines. Two of them exhibited an appreciable anti‐tumor activity in the low micromolar range, which opens new perspectives for therapeutic application on humans.

Piperidine-appended imidazolium ionic liquid as task-specific basic-IL for Suzuki and Heck reactions and for tandem Wittig-Suzuki, Wittig-Heck, Horner-Emmons-Suzuki, and Horner-Emmons-Heck protocols

Facile, high yielding, one-pot methods for the synthesis of a library of diversely substituted bi-aryls, diarylethenes, and aryl-enoates, via Suzuki and Heck reactions, and by sequential Wittig-Suzuki, Wittig-Heck, Horner-Emmons-Suzuki, and Horner-Emmons-Heck reactions are reported. The reactions employ piperidine-appended imidazolium ionic liquid [PAIM][NTf2] as a task-specific basic-IL, butyl-methyl-imidazolium ionic liquid [BMIM][X] (X=PF6, BF4) as solvent, and catalytic amounts of Pd(OAc)2, with no other additives. Wittig and Horner-Emmons reactions are effected by reacting substituted benzaldehydes with 4-bromobenzyl-PPh3 (or bromomethyl-PPh3) phosphonium salts, or diethylphosphonate with bromobenzaldehydes respectively, to form the corresponding ethenes. Subsequent cross-coupling reactions are accomplished by addition of aryl-boronic acid or phenyl-ethenes along with Pd(OAc)2 to bring about the aforementioned hyphenated transformations. The feasibility to perform double-olefination via Wittig and Horner-Emmons reactions with dialdehydes to form highly conjugated bis-styryl and bis-enoate compounds is also shown. The [BMIM][X] solvent is recycled and reused.

An Efficient Synthesis of Baricitinib

A highly efficient method for the synthesis of baricitinib was developed. The starting material tert-butyl 3-oxoazetidine-1-carboxylate was converted to intermediate 2-(1-(ethylsulfonyl)azetidin-3-ylidene)acetonitrile via the Horner–Emmons reaction, deprotection of the N-Boc-group and a final sulfonamidation reaction. Then the nucleophilic addition reaction was carried out smoothly to afford the borate intermediate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene under reflux. Finally, the desired compound baricitinib was obtained by the Suzuki coupling reaction of 4-chloro-7- H-pyrrolo[2,3- d]pyrimidine with the above borate intermediate. All compounds were characterised by IR, MS, 1H NMR and 13C NMR. The overall yield in this synthetic route was as high as 49%. Moreover, this procedure is straightforward to carry out, has low cost and is suitable for industrial production.

Synthesis of Novel 2′,3′-Difluorinated 5′-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

A novel route for the synthesis of 2′,3′-difluorinated 5′-deoxythreosyl phosphonic acid nucleosides from glyceraldehyde using the Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate is described. The second fluorination at the 2′-position was an electrophilic reaction performed using N-fluorodibenzenesulfonimide. Glycosylation reactions between the nucleosidic bases and glycosyl donor 9 generated nucleosides that were further phosphonated and hydrolyzed to produce the desired nucleoside analogues. The synthesized nucleoside analogues 13, 16, 20, and 23 were tested for anti- human immunodeficiency virus (HIV) activity as well as cytotoxicity. Adenine derivative 16 showed significant anti-HIV activity up to 100 μM.

Development of general methods for the synthesis of new substituted allyl bromides as promising alkenylating agents

A general procedure has been developed for the synthesis of hitherto unknown substituted allyl bromides. The procedure includes preparation of the corresponding α,β-unsaturated carboxylic acid esters from accessible ketones according to the Horner-Emmons reaction, reduction of these esters with diisobutylaluminum hydride to allylic alcohols, and substitution of the hydroxy group by bromine by the action of PBr3. The E,Z isomer ratio of the synthesized unsaturated compounds ranges from 3: 1 to 4: 1.

Synthesis of four diastereomers and structural revision of tetradenolide

Four diastereomers of tetradenolide, a cytotoxic α-pyrone isolated from Tetradenia riparia, were synthesized stereoselectively using the Z-selective Horner–Emmons reaction followed by acid catalyzed lactonization. Making comparison of the 1H and 13C NMR spectral data of the four diastereomers with those of the reported value of natural product did not lead to determine the relative stereochemistry of the natural tetradenolide. Thus detailed investigation of the spectral data of the related compounds led us to revise the structure of tetradenolide as deacetylboronolide.

ChemInform Abstract: Facile Synthesis of Pyrido[1,2‐a]benzimidazole Derivatives via Novel Tandem Reaction Involving Horner—Emmons Reaction.

AbstractTitle compounds of type (III) are prepared under mild conditions.

Novel analogues of resveratrol: metabolism and inhibition of colon cancer cell proliferation

Resveratrol is a phytochemical present in the skin of red grapes, and hence red wine as well as a variety of berries and nuts. It is an anti-oxidant, which has shown cancer chemopreventive properties in preclinical rodent models of carcinogenesis. The bioavailability of resveratrol is low, as it is rapidly metabolised to glucuronides and sulfates. The pharmacological activities of conjugate metabolites of phenols are often much lower than those of their metabolic progenitors. Therefore chemical synthetic manipulations aimed at slowing the rate of metabolic conjugation of phenols may generate analogues with increased bioavailability and efficacy. Here we describe the synthesis using the Wittig–Horner–Emmons reaction of a new series of resveratrol analogues in which the phenol moieties were systematically replaced by hydroxymethyl and/or methoxy groups. Incubation of analogues, which lack phenol groups with phase II metabolising enzyme preparations generated hardly any, or only small amounts of, conjugates. Four of the new analogue inhibited the growth of human-derived HCA-7 colon cancer cells, but with much less potency than resveratrol.

Synthesis and Conformation of Novel 4'-Fluorinated 5'-Deoxythreosyl Phosphonic Acid Nucleosides as Antiviral Agents

Efficient synthetic route to novel 4'-fluorinated 5'-deoxythreosyl phosphonic acid nucleosides was described from glyceraldehyde using Horner-Emmons reaction in the presence of triethyl α-fluorophosphonoacetate. Glycosylation reaction of nucleosidic bases with glycosly donor 14 gave the nucleosides which were further phosphonated and hydrolyzed to reach desired nucleoside analogues. Synthesized nucleoside analogues 18, 21, 25 and 28 were tested for anti-HIV activity as well as cytotoxicity. Adenine derivatives 18 and 21 showed significant anti-HIV activity up to 100 µM.

Synthesis of lipid II phosphonate analogues

Simple analogues of lipid II were synthesized from 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-β-d-glucopyranose using conjugate addition onto ethylidene bisphosphonate and subsequent Wadsworth–Horner–Emmons reaction with long chain aliphatic aldehydes.

ChemInform Abstract: Use of Phosphonyl Carbanions in the Synthesis of Antiinflammatory Active Phosphorus‐Containing Fused Heterocycles and Relevance Phosphonates.

AbstractA variety of phosphorus‐containing bicyclic 5,5‐ and 5,6‐membered systems are synthesized by Horner—Emmons reactions of 2‐acetylfuran (I) or ‐thiophene (V).

Total Synthesis of Tyrosine‐Derived Tetramic Acid Pigments from a Slime Mould

AbstractA method for the total synthesis of naturally occurring 3‐enoyltetramic acids derived from L‐tyrosine is described, allowing for three chemical transformations to occur in one pot by using a multicomponent mixture. The sequence involves (1) a base‐promoted Lacey–Dieckmann condensation, (2) a Michaelis–Becker reaction, and (3) a Wittig–Horner–Emmons reaction between the resulting 3‐phosphonoacetyltetramic acid and an appropriate aldehyde. This sequence of reactions was applied to the synthesis of polyenic pigments obtained from the slime mould Leocarpus fragilis starting from readily available precursors. A series of structurally related compounds was also synthesized and their antibiotic significance was evaluated to elucidate their role in nature.

Synthesis and characterization of soluble indolo[3,2- b]carbazole derivatives for organic field-effect transistors

The synthesis and characterization of new soluble materials based on the indolo[3,2- b]carbazole (IC) framework is presented. These new molecules are particularly suitable for p-channel organic field-effect transistors (OFETs) because of the high level of crystallinity usually found in IC derivatives. To obtain soluble materials, the synthesis of new 2- or 3-bromoindolo[3,2- b]carbazole backbone was performed which allowed the synthesis of molecule bearing the IC moieties on both ends. Either Suzuki cross-coupling or Horner–Emmons reaction were used as the final step. Thin films of these new materials, along with 3,9-diphenyl-5,11-dioctylindolo[3,2- b]carbazole (3POIND), a material previously reported, were obtained by using different processing techniques. Polarized optical microscopy (POM) and X-ray diffraction (XRD) experiments on these solution-processed films showed high crystallinity. Transistors fabricated with these thin films gave a hole mobility as high as 0.06 cm 2 V −1 s −1 with drop-cast films and 0.12 cm 2 V −1 s −1 when the films were processed with the shearing technique.

Synthesis and properties of cyclic ethylene-bridged 3,6-fluorene dimer and its linear analogues

Three oligomers of ethylene-bridged 3,6-fluorene were synthesized starting from phenanthrenequinone. McMurry reaction was applied to synthesize the cyclic compound. Horner–Emmons reaction was used to synthesize the linear compounds with all-trans configuration. The crystal structure of the cyclic compound was described. The optical and electronic properties of these compounds were fully characterized and compared.

ChemInform Abstract: Horner-Emmons Reaction in the Synthesis of Esters of Unsaturated Acids from Adamantane Series and Related Carcass Compounds.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Synthesis of Activated Alkenes Bearing the Difluoromethylenephosphonate Group: A Range of Building Blocks for the Synthesis of Secondary Difluorophosphonates.

Active methylene compounds reacted readily with stable hydrate 2-diethoxyphosphoryl-2,2-difluoroethane-1,1-diol to afford a range of activated alkenes bearing the difluoromethylenephosphonate group, a useful motif in the synthesis of phosphate ester mimics of biological interest. Wadsworth–Horner–Emmons reactions were employed using modified Rathke conditions for the syntheses of alkenoates, an alkenoic acid and a vinyl sulfone, while a Henry reaction followed by E1cB dehydration afforded an enedioate and a nitroalkene. A vinyl sulfoxide was less straightforward to synthesise and dephosphorylation to a difluoromethyl congener accompanied attempts to force the reaction to completion.

ChemInform Abstract: Solid‐Phase Reactive Chromatography (SPRC): A New Methodology for Wittig and Horner—Emmons Reactions on a Column under Microwave Irradiation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Poly(3-dodedyl-2,5-thienylenevinylene)s from the Stille coupling and the Horner–Emmons reaction

Regioregular (RR) conjugated polymers are critical for electronic and optoelectronic properties of polymer based semiconducting devices. Monosubstituted polythienylvinylene (PTV), a relatively low band-gap conjugated polymer, has been reportedly synthesized using the Stille coupling reaction between 3-dodecyl-2,5-dibromothiophene and (E)-1,2-bis(tributylstannyl)ethylene. Although a small fraction of the product shows good (∼90%) regioregularity, the whole product (S-C12-PTV) consists of mostly unidentified structures. To gain better control of the polymer structure and regioregularity, a difunctionalized C12-thiophene monomer, 3-dodecyl-5-formyl-thiophen-2-ylmethyl)-phosphonic acid diethyl ester, has been polymerized in near quantitative yield via the Horner–Emmons reaction. The full (100%) regioregularity of the resulting polymer (HE-C12-PTV) has been confirmed by its 1H and 13C NMR spectra. The full regioregularity is also reflected in its strong tendency to crystallize and practically no solubility in boiling hexane, in sharp contrast to S-C12-PTV. UV-vis absorption spectroscopy, fluorescence spectroscopy, cyclovoltammetry, thermal analysis (DSC & TGA) and X-ray diffraction have been used to characterize both polymers. UV-vis absorption spectra of the HE-C12-PTV chloroform solutions of different concentrations show well-resolved vibronic structures with an absorption maximum at 577 nm and a prominent shoulder at 614 nm. The optical bandgaps are 1.80 eV in chloroform solution and 1.65 eV in film. The HOMO/LUMO energy levels of the HE-C12-PTV film were found to be at −4.98 eV and −2.88 eV, respectively. The electrochemical bandgap of the polymer in the film is estimated to be 2.1 eV. The DSC curve shows a pronounced melting peak at 205 °C. XRD study shows that a decent crystalline structure is formed without any annealing of the as-cast films.

Solid‐Phase Reactive Chromatography (SPRC): A New Methodology for Wittig and Horner–Emmons Reactions on a Column under Microwave Irradiation

AbstractA new methodology named solid‐phase reactive chromatography (SPRC), which combines reaction, separation, and purification into a single unit for the preparation of small samples, is described. This method was illustrated in the synthesis of some natural bioactive compounds, namely, methoxylated analogues of resveratrol, alkylresorcinols, and 5‐aryl‐2,4‐pentadienoates, over a column of alumina‐KF under microwave irradiation by using the Wittig and Horner–Emmons reactions. This approach permitted the preparation of the target olefins with high purity and good to excellent yields in short reaction times.