Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

Synthesis of Halogenated α,β‐Unsaturated γ‐Butyrolactone Derivatives by Triphenylphosphine‐Catalyzed Cyclization of α‐Halogeno Ketones with Dialkyl Acetylenedicarboxylates (=Dialkyl But‐2‐ynedioates)

A Ph₃P‐catalyzed cyclization of α‐halogeno ketones 2 with dialkyl acetylenedicarboxylates (=dialkyl but‐2‐ynedioates) 3 produced halogenated α,β‐unsaturated γ‐butyrolactone derivatives 4 in good yields (Scheme 1, Table). The presence of electron‐withdrawing groups such as halogen atoms at the α‐position of the ketones was necessary in this reaction. Cyclization of α‐chloro ketones resulted in higher yields than that of the corresponding α‐bromo ketones. Dihalogeno ketones similarly afforded the expected γ‐butyrolactone derivatives in high yields.     

Secondary Amine‐Catalyzed Asymmetric γ‐Alkylation of α‐Branched Enals via Dienamine Activation

The direct and enantioselective γ‐alkylation of α‐substituted α,β‐unsaturated aldehydes proceeding under dienamine catalysis is described. We have found that the Seebach modification of the diphenyl‐prolinol silyl ether catalyst in combination with saccharin as an acidic additive promotes an S_N1 alkylation pathway, while ensuring complete γ‐site selectivity and a high stereocontrol. Theoretical and spectroscopic investigations have provided insights into the conformational behavior of the covalent dienamine intermediate derived from the condensation of 2‐methylpent‐2‐enal and the chiral amine. Implications for the mechanism of stereoinduction are discussed.     

Tandem Benzylic Oxidation/Dihydroxylation of α‐Vinyl‐ and α‐Alkenylbenzyl Alcohols

A de novo tandem benzylic oxidative dihydroxylation of α‐vinyl‐ and α‐alkenylbenzyl alcohols has been developed to give α,β‐dihydroxypropiophenones (=2,3‐dihydroxy‐1‐phenylpropan‐1‐ones) and α,β‐dihydroxyalkyl phenones. This method was shown to be substrate‐selective and specific for the oxidation of benzylic alcohols.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.     

The kinetics of polycondensation of α,α′‐dichloro‐p‐xylene with 4,4′‐isopropylidenediphenol using benzyltriethylammonium chloride as a phase‐transfer catalyst

The phase‐transfer catalyzed polycondensation of α,α′‐dichloro‐p‐xylene with 4,4′‐isopropylidenediphenol was carried out using benzylethylammonium chloride in a two‐phase system of an aqueous alkaline solution and benzene at 60 °C under nitrogen atmosphere. The rate of polycondensation was expressed as the combined terms of quaternary onium cation and 4,4′‐isopropylidenediphenolate anion rather than the feed concentration of catalyst and 4,4′‐isopropylidenediphenol. The measured concentrations of hydroxide and chloride anion in the aqueous solution and α,α′‐dichloro‐p‐xylene in the organic phase were used to obtain the reaction rate constant with the integral method, and to analyze the polycondensation mechanism with a cyclic phase‐transfer initiation step in the heterogeneous liquid–liquid system. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3059–3066, 2000     

Analogues of α‐Campholenal (= (1R)‐2,2,3‐Trimethylcyclopent‐3‐ene‐1‐acetaldehyde) as Building Blocks for (+)‐β‐Necrodol (= (1S,3S)‐2,2,3‐Trimethyl‐4‐methylenecyclopentanemethanol) and Sandalwood‐like Alcohols

To complete our panorama in structure–activity relationships (SARs) of sandalwood‐like alcohols derived from analogues of α‐campholenal (= (1R)‐2,2,3‐trimethylcyclopent‐3‐ene‐1‐acetaldehyde), we isomerized the epoxy‐isopropyl‐apopinene (?)‐ 2d to the corresponding unreported α‐campholenal analogue (+)‐ 4d (Scheme 1). Derived from the known 3‐demethyl‐α‐campholenal (+)‐ 4a , we prepared the saturated analogue (+)‐ 5a by hydrogenation, while the heterocyclic aldehyde (+)‐ 5b was obtained via a Bayer‐Villiger reaction from the known methyl ketone (+)‐ 6 . Oxidative hydroboration of the known α‐campholenal acetal (?)‐ 8b allowed, after subsequent oxidation of alcohol (+)‐ 9b to ketone (+)‐ 10 , and appropriate alkyl Grignard reaction, access to the 3,4‐disubstituted analogues (+)‐ 4f,g following dehydration and deprotection. (Scheme 2). Epoxidation of either (+)‐ 4b or its methyl ketone (+)‐ 4h , afforded stereoselectively the trans‐epoxy derivatives 11a,b , while the minor cis‐stereoisomer (+)‐ 12a was isolated by chromatography (trans/cis of the epoxy moiety relative to the C₂ or C₃ side chain). Alternatively, the corresponding trans‐epoxy alcohol or acetate 13a,b was obtained either by reduction/esterification from trans‐epoxy aldehyde (+)‐ 11a or by stereoselective epoxidation of the α‐campholenol (+)‐ 15a or of its acetate (?)‐ 15b , respectively. Their cis‐analogues were prepared starting from (+)‐ 12a . Either (+)‐ 4h or (?)‐ 11b , was submitted to a Bayer‐Villiger oxidation to afford acetate (?)‐ 16a . Since isomerizations of (?)‐ 16 lead preferentially to β‐campholene isomers, we followed a known procedure for the isomerization of (?)‐epoxyverbenone (?)‐ 2e to the norcampholenal analogue (+)‐ 19a . Reduction and subsequent protection afforded the silyl ether (?)‐ 19c , which was stereoselectively hydroborated under oxidative condition to afford the secondary alcohol (+)‐ 20c . Further oxidation and epimerization furnished the trans‐ketone (?)‐ 17a , a known intermediate of either (+)‐β‐necrodol (= (+)‐(1S,3S)‐2,2,3‐trimethyl‐4‐methylenecyclopentanemethanol; 17c ) or (+)‐(Z)‐lancifolol (= (1S,3R,4Z)‐2,2,3‐trimethyl‐4‐(4‐methylpent‐3‐enylidene)cyclopentanemethanol). Finally, hydrogenation of (+)‐ 4b gave the saturated cis‐aldehyde (+)‐ 21 , readily reduced to its corresponding alcohol (+)‐ 22a . Similarly, hydrogenation of β‐campholenol (= 2,3,3‐trimethylcyclopent‐1‐ene‐1‐ethanol) gave access via the cis‐alcohol rac‐ 23a , to the cis‐aldehyde rac‐ 24 .     

A Novel Synthesis of γ,δ‐Unsaturated Aldehydes from α‐Formyl‐γ‐lactones

A preparatively useful one‐step transformation of γ,γ‐disubstituted α‐formyl‐γ‐lactones into trisubstituted γ,δ‐unsaturated aldehydes is described, by means of catalytic amounts of either AcOH or AcOEt in the vapor phase over a glass support. A mechanistic rationale is proposed.     

Synthesis of β‐Hydroxy α‐Sulfanyl Esters by Using Nanocrystalline Magnesium Oxide

Aldol‐type reaction between electron deficient aldehydes and sulfonium salts to afford the corresponding β‐hydroxy α‐sulfanyl esters in moderate‐to‐good yields by using nanocrystalline MgO is described. The sulfanyl group is a useful group for further transformations in organic synthesis. Low R_f‐value isomer is anti‐configured as revealed by X‐ray diffraction study and consistent with the assignment of ¹H‐NMR spectrum.     

A Novel Organocatalytic Asymmetric Transfer Hydrogenation of α,β‐Unsaturated Aldehydes

α,β‐Unsaturated aldehydes reacted with diimide (diazene) in the presence of optically active ammonium salt 1 as a catalyst to give the corresponding saturated aldehydes in excellent yields and up to 98 : 2 er. Attractive features of the asymmetric transfer hydrogenation are its high yields, and chemo‐, and enantioselectivities.     

Rhodium Fluoroapatite Catalyzed Conjugate Addition of Arylboronic Acids to α,β‐Unsaturated Carbonyl Compounds

Rhodium fluoroapatite (RhFAP) is an efficient catalyst for conjugate addition of organoboron reagents to α,β‐unsaturated carbonyl compounds. A variety of arylboronic acids and α,β‐unsaturated carbonyl compounds were converted to the corresponding conjugate‐addition products, demonstrating the versatility of the reaction. The reaction is highly selective. RhFAP was recovered quantitatively by simple filtration, and reused for four cycles.     

Base‐Induced Decarboxylation of Polyunsaturated α‐Cyano Acids Derived from Malonic Acid: Synthesis of Sesquiterpene Nitriles and Aldehydes with β‐, φ‐, and ψ‐End Groups

Catalytic base‐induced decarboxylation of polyunsaturated α‐cyano‐β‐methyl acids derived from malonic acid led to the corresponding nitriles 3 (Schemes 2 and 3), 6 (Scheme 5), and 9 (Scheme 6). This decarboxylation occurred with previous deconjugation of the α,β‐alkene moiety of the α‐cyano‐β‐methyl acid, leading to an α‐cyano‐β‐methylene propanoic acid which was easily decarboxylated (see Scheme 2). β‐Methylene intermediates, in some cases, could be isolated; mechanistic pathways are proposed. The nitriles 3, 6 , and 9 were reduced to the sesquiterpene aldehydes 4 (β‐end group), 7 (φ‐end group), and 10 (ψ‐end group), respectively.     

cis‐trans Peptide‐Bond Isomerization in α‐Methylproline Derivatives

α‐Methyl‐L ‐proline is an α‐substituted analog of proline that has been previously employed to constrain prolyl peptide bonds in a trans conformation. Here, we revisit the cis‐trans prolyl peptide bond equilibrium in derivatives of α‐methyl‐L ‐proline, such as N‐Boc‐protected α‐methyl‐L ‐proline and the hexapeptide H‐Ala‐Tyr‐αMePro‐Tyr‐Asp‐Val‐OH. In Boc‐α‐methyl‐L ‐proline, we found that both cis and trans conformers were populated, whereas, in the short peptide, only the trans conformer was detected. The energy barrier for the cis‐trans isomerization in Boc‐α‐methyl‐L ‐proline was determined by line‐shape analysis of NMR spectra obtained at different temperatures and found to be 1.24 kcal/mol (at 298 K) higher than the corresponding value for Boc‐L ‐proline. These findings further illuminate the conformationally constraining properties of α‐methyl‐L ‐proline.     

Palladium‐catalyzed carbonylative cyclization of β‐bromo‐α,β‐unsaturated carboxylic acids with 2,2‐dimethylhydrazine leading to 1‐(dimethylamino)‐1H‐pyrrole‐2,5‐diones

β‐Bromo‐α,β‐unsaturated carboxylic acids are carbonylatively cyclized with 2,2‐dimethylhydrazine under carbon monoxide pressure in THF in the presence of a catalytic amount of a palladium catalyst along with a base to give 1‐(dimethylamino)‐1H‐pyrrole‐2,5‐diones. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis of α‐(Fluorophenyl)pyridine by Palladium‐Catalyzed Cross‐Coupling Reaction

A series of α‐(fluoro‐substituted phenyl)pyridines have been synthesized by means of a palladium‐catalyzed cross‐coupling reaction between fluoro‐substituted phenylboronic acid and 2‐bromopyridine or its derivatives. The reactivities of the phenylboronic acids containing di‐ and tri‐fluoro substituents with α‐pyridyl bromide were investigated in different catalyst systems. Unsuccessful results were observed in the Pd/C and PPh₃ catalyst system due to phenylboronic acid containing electron‐withdrawing F atom(s). For the catalyst system of Pd(OAc)₂/PPh₃, the reactions gave moderate yields of 55% –80%, meanwhile, affording 10% –20% of dimerisation (self‐coupling) by‐products, but trace products were obtained in coupling with 2,4‐difluorophenylboronic acids because of steric hinderance. Pd(PPh₃)₄ was more reactive for boronic acids with sterically hindering F atom(s), and the coupling reactions gave good yields of 90% and 91% without any self‐coupling by‐product.     

Synthesis,characterization and α‐amylase and α‐glucosidase inhibition studies of novel vanadyl chalcone complexes

A series of chalcone ligands and their corresponding vanadyl complexes of composition [VO (L^I–IV)₂(H₂O)₂]SO₄ (where L^I = 1,3‐Diphenylprop‐2‐en‐1‐one, L^II = 3‐(2‐Hydroxy‐phenyl)‐1‐phenyl‐propenone, L^III = 3‐(3‐Nitro‐phenyl)‐1‐phenyl‐propenone, L^IV = 3‐(4‐Methoxy‐phenyl)‐1‐phenyl‐propenone) have been synthesized and characterized using various spectroscopic (Fourier‐transform infrared, electrospray ionization mass, nuclear magnetic resonance, electron paramagnetic resonance, thermogravimetric analysis, vibrating sample magnetometer) and physico‐analytic techniques. Antidiabetic activities of synthesized complexes along with chalcones were evaluated by performing in vitro and in silico α‐amylase and α‐glucosidase inhibition studies. The obtained results displayed moderate to significant inhibition activity against both the enzymes by vanadyl chalcone complexes. The most potent complexes were further investigated for the enzyme kinetic studies and displayed the mixed inhibition for both the enzymes. Further, antioxidant activity of vanadyl chalcone complexes was evaluated for their efficiency to release oxidative stress using 2,2‐diphenyl‐1‐picryl‐hydrazyl‐hydrate assay, and two complexes (Complexes 2 and 4 ) have demonstrated remarkable antioxidant activity. All the complexes were found to possess promising antidiabetic and antioxidant potential.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.     

Hydrolytic degradation of poly(ε‐caprolactone) with different end groups and poly(ε‐caprolactone‐co‐γ‐butyrolactone): characterization and kinetics of hydrocortisone delivery

Asymmetric telechelic α‐hydroxyl‐ω‐(carboxylic acid)‐poly(ε‐caprolactone) (HA‐PCL), α‐hydroxyl‐ω‐(benzylic ester)‐poly(ε‐caprolactone) (HBz‐PCL), and an asymmetric telechelic copolymer α‐hydroxyl‐ω‐(carboxylic acid)‐poly(ε‐caprolactone‐co‐γ‐butyrolactone) (HA‐PCB) were synthesized by ring‐opening polymerization of ε‐caprolactone (CL). CL and CL/γ‐butyrolactone mixture were used to obtain homopolymers and copolymer respectively at 150°C and 2 hr using ammonium decamolybdate (NH₄) [Mo₁₀O₃₄] (Dec) as a catalyst. Water (HA‐PCL and HA‐PCB) or benzyl alcohol (HBz‐PCL) were used as initiators. The three polylactones reached initial molecular weights between 2000 and 3000 Da measured by proton nuclear magnetic resonance (¹H‐NMR). Compression‐molded polylactone caplets were allowed to degrade in 0.5 M aqueous p‐toluenesulfonic acid at 37°C and monitored up to 60 days for weight loss behavior. Data showed that the copolymer degraded faster than the PCL homopolymers, and that there was no difference in the weight loss behavior between HA‐PCL and HBz‐PCL. Caplets of the three polylactones containing 1% (w/w) hydrocortisone were placed in two different buffer systems, pH 5.0 with citrate buffer and pH 7.4 with phosphate buffer at 37°C, and monitored up to 50 days for their release behavior. The release profiles of hydrocortisone presented two stages. The introduction of a second monomer in the polymer chain significantly increased the release rate, the degradation rate for HA‐PCB being faster than those for HBz‐PCL and HA‐PCL. At the pH studied, only slight differences on the liberation profiles were observed. SEM micrographs indicate that hydrolytic degradation occurred mainly by a surface erosion mechanism. Copyright © 2009 John Wiley & Sons, Ltd.     

Selective α-Bromination of β-Keto Esters in Reusable PEG-400 under Mild and Catalyst-free Conditions

An efficient bromination protocol for the synthesis of α-bromo-β-keto esters has been developed. In PEG-400 （poly（ethylene glycol-400））, a variety of β-keto esters were treated with NBS （N-bromosuccinimide） at room temperature to selectively afford the corresponding α-monobromination products in excellent yields. It is noteworthy that the reaction was conducted under mild, environmentally benign and catalyst-free conditions.     

Design and Synthesis of α,β‐Epoxyketones as New Anticancer Agents

As epoxy functional group has high anticancer activity, α,β‐epoxyketones were designed and synthesized as new anticancer agents, and their structures were confirmed by UV, ¹H NMR, IR, MS technigeces and elemental analysis. Their in vitro anticancer activities were evaluated by MTT method and the results showed that the compound 4c exhibited good activity with IC₅₀ of 17.8, 22.0 and 24.1 µg/mL against A‐549, Hela and HepG2 cells, respectively. The dose of LD50 of the mice by intragastric administration was 1864.4 mg/kg. Therefore, the α,β‐epoxyketones could potentially provide as new anticancer agents.