Propiolic Esters Research Articles

Oxidative Alkoxycarbonylation of Alkynes by Means of Aryl α‐Diimine Palladium(II) Complexes as Catalysts

AbstractThe straightforward in situ synthesized bis(2,6‐diisopropyl)acenaphthenequinonediimine palladium triflate catalyst was generally employed for both the mono‐alkoxycarbonylation of terminal alkynes, and the bis‐alkoxycarbonylation of 1,2‐disubstituted alkynes by using mild reaction conditions [carbon monoxide pressure (PCO)=4 bar, temperature=20 °C]. Utilizing low catalyst loading (down to 0.5 mol%), a variety of propiolic esters were synthesized with good to excellent isolated yields. Most importantly the system was very efficient not only with methanol but also with a range of different alcohols, starting from the less hindered benzyl alcohol to the most hindered ones, such as isopropyl alcohol and tert‐butyl alcohol. In addition, aromatic and aliphatic 1,2‐disubstituted alkynes were converted into maleic acid derivatives, together with an acid‐catalyzed isomerization reaction, showing modest to good selectivity and excellent combined yields. In particular 3‐hexyne showed a satisfactory degree of selectivity for the maleic diesters of methanol and benzyl alcohol, obtaining the corresponding products with good isolated yields.magnified image

Investigation of the Pyridinium Ylide--Alkyne Cycloaddition as a Fluorogenic Coupling Reaction.

The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases) was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.). Electron-withdrawing substituents, lowering the acid dissociation constant (pKa) of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature.

Synthesis of Isomeric Dimers of Deoxycholic Acid Derivatives Linked by 1,2,3-Triazole

Steroidal propargylic ester 6 and the propiolic ester 7 were prepared in a few steps from the deoxycholic acid. The Huisgen cycloaddition reaction of alkynes 6 and 7 as dipolarophiles with a 1,3-dipolar compound, the azide 5, afforded the dimeric compounds 8 and 9, respectively, in good yield. The dimers of deoxycholic acid derivatives linked by 1,4-disubstituted 1,2,3-triazole were characterized by spectroscopic methods.

ChemInform Abstract: Diastereoselective Construction of Tetrahydropyridine Fused Bicyclic Structures via Three‐Component Domino Reaction.

AbstractA three‐component reaction of aminoalcohols, propiolic esters, and α,β‐unsaturated aldehydes is developed to permit the highly diastereoselective synthesis of a range of tetrahydropyridine fused heterocycles.

Platinum- and gold-catalyzed hydroalkoxylation and tetramerization of propiolate esters

PtCl2 was found to efficiently catalyze intermolecular additions of propiolate esters with alcohols. The reaction of propiolate esters and alcohols in the presence of PtCl2 gave (E)-vinyl ethers as the major products at 60°C, whereas alkyl 3,3-dialkoxypropanoates were predominantly obtained when the reaction temperature was set to 80°C. On the other hand, a novel regioselective tetramerization of propiolate esters catalyzed by AuCl3 under mild conditions afforded 1,2,5,6-tetrasubstituted-cyclooctatetraene (1,2,5,6-COT) in moderate yields.

Total Syntheses of the Coumarin-Containing Natural Products Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular Hydroarylation (IMHA) Chemistry

The title natural products (1 and 2, respectively) have been synthesized by Au(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., 13), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)propiolic acid or propiolic acid and N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (3) was readily derived from fraxetin (2) by established procedures.

Synthesis of 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic Acid and (E)-3-(1-Methyl-1H-imidazol-2-ylthio)acrylic Acid

The syntheses of 3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid and 3-(1-methyl-1H-imidazol-2-ylthio)propanoic acid, mitochondria-targeted prodrugs of the antioxidant methimazole, are described. The method of Fan et al. (Synthesis 2006, 2286) for the reaction of phenols with propiolic acid and propiolate esters was modified to synthesize (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylic acid. The intermediate tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate was prepared by the reaction of tert-butyl propiolate with methimazole; the use of tert-butyl propiolate rather than methyl propiolate gave tert-butyl (E)-3-(1-methyl-1H-imidazol-2-ylthio)acrylate as the predominant isomer. Acid hydrolysis of the intermediate ester afforded the target compound. 3-(1-Methyl-1H-imidazol-2-ylthio)propanoic acid was synthesized from 3-bromopropanoic acid and methimazole under conditions that gave preferential substitution on sulfur and minimized substitution on nitrogen.

Development of a triazole-cure resin system for composites: Evaluation of alkyne curatives

We are developing a resin system that cures via triazole ring formation (cycloaddition reaction of azides with terminal alkynes) instead of the traditional oxirane/amine reaction. The high exothermicity of the azido/alkyne reaction is expected to yield higher extents of reaction under ambient-cure conditions, making the resin system potentially suitable for “out-of-autoclave” curing processes. The difunctional azide-terminated resin, di(3-azido-2-hydroxypropyl) ether of bisphenol-A, was selected as the baseline diazide. A number of alkyne crosslinkers were synthesized and characterized, including propiolate esters of di- and trifunctional alcohols, propargyl esters of di- and trifunctional carboxylic acids, propargyl ethers of di- and trifunctional alcohols, and N,N,N′,N′-tetrapropargyl derivatives of primary diamines. Commercially available tripropargyl amine was also studied. Those systems employing a propiolate-based alkyne were found to be much more reactive toward the Huisgen 1,3-dipolar cycloaddition than the propargyl species. Curing energetics as a function of alkyne type, investigated through a dynamic differential scanning calorimetry approach, showed a distinct divide between the averaged activation energies of the propiolate and propargyl-type crosslinkers, 69.2–73.6 kJ/mol versus 82.3–86.4 kJ/mol, respectively. Cured network properties were readily manipulated through the incorporation of varying amounts of di- versus tri- and tetra-functional alkynes or through incorporation of soft alkylene and alkyleneoxy versus rigid aromatic polyalkynes. As expected, mechanical properties, e.g., the temperature of the tan δ peak in dynamic mechanical analysis, were found to increase with increasing crosslink density. These results have allowed us to select the most promising systems for scale-up and fabrication of samples of both pure resin and composites for traditional mechanical property testing, which will be reported in a subsequent paper.

SYNTHESIS AND CHARACTERIZATION OF OPTICAL-ACTIVE AND AMPHIPHILIC GRAFT COPOLYMERS OF POLYACETYLENE-MPEG

The novel graft copolymers of(poly(a-co-b),(a:propiolic acid L-menthol ester;b:propiolic acid polyethylene glycol monomethyl ether ester)) having C-chirality and hydrophilic macromolecules as pendant groups were synthesized via copolymerization of monomer a and monomer b by using(nbd)Rh +[η6-C6H5B-(C6H5)3]as catalyst.The structure of copolymers was characterized by FTIR.Moderate molecular weights(Mn)(13000 ～ 15000) and Mw /Mn(2.1 ～ 2.2) of copolymers were measured by GPC.The maximum amount of MPEG for successful copolymerization of copolymers was 20 mol%.The optical activity and secondary structure of the copolymers were characterized by specific rotations([α]D) and circular dichroism(CD) spectra.The copolymers with relatively low yields(32.3% ～ 46.6%) exhibited high optical activity in contrast to chiral monomer,which accorded with the"Chiral Amplification"effect.All the copolymers formed single helical conformation in despite of adding the long chain of MPEG.Certainly,the optical activity of copolymers decreased with the increase of MPEG content.The helical conformation of the copolymers kept the better stability in CHCl3 comparing to other three selective solvents.As the time delay,the optical activity of the copolymers decreased due to their instability.By adding the hydrophilic chain of MPEG,rigid and flexible chain were linked finely and formed the hydrophilic /hydrophobic interaction,which provided the best driving force for self-assembly behavior.

ChemInform Abstract: A Convenient Procedure for the Preparation of 3-Bromopropiolic Esters.

Abstract 3-Bromopropiolic esters are efficiently prepared by reaction of the corresponding propiolic esters with N-bromosuccinimide in acetone and silver nitrate as catalyst.

ChemInform Abstract: Preparation and Novel Cycloaddition Reactions of 7-Dimethylamino-1H- azepin-3(2H)-one.

A convenient preparation of the functionalised azepinone 3 is reported: this compound reacts with acid to give a stable mixture of O- and C-protonated materials, it gives the substitution product 4 on reaction with methoxymethylene Meldrum's acid 5, and on treatment with propiolic ester gives a 1,3,4-trisubstituted pyrrole 6 by a novel cycloaddition-condensation sequence.

Derivatization of thiols under flow conditions using two commercially available propiolate esters

In the present study we report new data on the reaction of three representative thiols – captopril (CAP), cysteine (CYS) and N-acetylcysteine (NAC) – with two commercially available propiolate esters – methyl-propiolate (MP) and butyl-propiolate (BP) – under flow conditions. The reactions were investigated on-line using sequential injection analysis (SI) and the formed derivatives were monitored spectrophotometrically at 285 nm. The effect of critical parameters of the reaction such as the pH, the temperature and the amount concentration of the reagents were studied in detail including stopped-flow (SF) experiments. Both reagents were found to be suitable for the automated derivatization of thiols, although MP offered faster kinetics compared to BP. The applicability of the procedures was demonstrated by the development of SI methods for the dissolution studies of CAP tablets with satisfactory results.

Vicinal Functionalization of Propiolate Esters via Catalytic Carbocupration: Stereoselective Formation of Substituted Vinyl Silanes

The vicinal functionalization of propiolate esters via a catalytic carbocupration-silicon group migration sequence has been investigated. We have observed that catalyst loadings as low as 5 mol % allow for good yields and excellent diastereoselectivities (>20:1) with a series of Grignard reagents for the synthesis of substituted E-vinyl silanes.

An efficient chemoselective synthesis of O-vinylaryl systems using acetylenic esters and dihydroxybenzenes in the presence of triphenylphosphine or alkyl isocyanides

The addition of 2,4-dihydroxyaceto(and benzo)phenone to propiolic ester is catalyzed by triphenylphosphine or tert-butyl isocyanide to form O-vinyl aryl derivatives in fairly good yields.

The reaction of photochemically generated α-hydroxyalkyl radicals with alkynes: a synthetic route to γ-butenolides

The photomediated generation of α-hydroxyalkyl radicals from simple acyclic and cyclic alcohols, and acyclic diols, and their subsequent carbon-carbon bond forming reaction with propiolate esters and acetylenedicarboxylates, gives a mixture of a β-(hydroxyalkyl)enoate, the result of a formal cis addition, and the unsaturated lactone (γ-butenolide) resulting from the spontaneous cyclization of the corresponding trans addition product. Treatment of the cis adduct with NBS converts it to the same lactone, and so the method overall constitutes a particularly direct route to this important structural unit. Cyclic alcohols give rise to spiro-γ-butenolides. The use of supported photomediators simplifies product isolation and allows for the recovery and reuse of the photomediator.

Vicinal Functionalization of Propiolate Esters via a Tandem Catalytic Carbocupration−Mukaiyama Aldol Reaction Sequence

The vicinal functionalization of propiolate esters via a tandem catalytic carbocupration-Mukaiyama aldol reaction sequence has been investigated. It has been shown that catalyst loadings as low as 8 mol % readily allow for good yields and excellent diastereoselectivities (>20:1) for a series of Grignard reagents and aldehydes.

One-Pot Synthesis of Fluorescent 2,5-Dihydro-1,2,3-triazine Derivatives from a Cascade Rearrangement Sequence in the Reactions of 1,2,3-Triazolium-1-aminide 1,3-Dipoles with Propiolate Esters

The reactions of 1,2,3-triazolium-1-aminides 1 (readily available from benzil bishydrazones) with propiolate esters leads to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 2, 3 in one pot. These synthetic reactions can be carried out in acetone, in water, or under solvent-free conditions. The reactions involve a Huisgen cycloaddition followed by a sequence of rearrangements. The final ring-expansion step was blocked by linking a six-methylene hydrocarbon chain between the prospective 1,2,3-triazine C-4 and C-6 atoms, using substrate 8 which gave the fused tricyclic azapropellane product 9 exclusively. X-ray crystal structures were determined for two 2,5-dihydro-1,2,3-triazine derivatives and for compound 9. The UV absorption of the 1,2,3-triazine derivatives showed a dual absorption at ca. 310 and ca. 390 nm with fluorescent emission at ca. 480 and 528 nm (for excitation at 317 nm). The significant Stokes shift of ca. 200 nm shows the potential for biological fluorescent labeling experiments.

Regioselective Hydrosilylations of Propiolate Esters with Tris(trimethylsilyl)silane.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Coumarins Catalyzed by Heterobimetallic Co/Rh Nanoparticles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Regioselective Synthesis of Fluoroalkylated [1,2,3]‐Triazoles by Huisgen Cycloaddition.

AbstractFor Abstract see ChemInform Abstract in Full Text.