- Lanthanide-Catalyzed Tandem Addition of Amines to Cyanoalkenes: Synthesis of Cyclic Amidines
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A tandem insertion of aliphatic nitriles and unactivated alkenes to the N-H bond of secondary aliphatic amines catalyzed by simple trialkyl rare-earth metal complexes was disclosed. This reaction provides a highly atom-economic and stereoselective way to a range of cyclic amidines under mild reaction conditions.
- Hou, Jinsong,Yang, Gaosheng,Chai, Zhuo
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p. 453 - 463
(2022/01/04)
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- Photocatalyzed Diastereoselective Isomerization of Cinnamyl Chlorides to Cyclopropanes
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Endergonic isomerizations are thermodynamically unfavored processes that are difficult to realize under thermal conditions. We report a photocatalytic and diastereoselective isomerization of acyclic cinnamyl chlorides to strained cyclopropanes. Quantum mechanical calculations (uM06-2X and DLPNO), including TD-DFT calculations, and experimental studies provide evidence for the energy transfer from an iridium photocatalyst to the allylic chloride substrate followed by C-Cl homolytic cleavage. Subsequent Cla¢ radical migration forms a localized triplet 1,3-diradical intermediate that, after intersystem crossing, undergoes ring-closing to form the desired product. The mild reaction conditions are compatible with a broad range of functional groups to generate chlorocyclopropanes in high yields and diastereoselectivities. A more efficient process is developed by addition of a catalytic amount of a nickel complex, and we propose a novel role for this cocatalyst to recycle an allyl chloride byproduct generated in the course of the reaction. The reaction is also shown to be stereoconvergent, as an E/Z mixture of cinnamyl chlorides furnish the anti-chlorocyclopropane product in high diastereoselectivity. We anticipate that the use of a visible light activated photocatalyst to transform substrates in combination with a transition metal catalyst to recycle byproducts back into the catalytic cycle will provide unique opportunities for the discovery of new reactivity.
- Dykstra, Ryan,Gutierrez, Osvaldo,Martin, Robert T.,Tambar, Uttam K.,Troian-Gautier, Ludovic,Xu, Bin
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supporting information
p. 6206 - 6215
(2020/04/27)
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- Intramolecular photocycloaddition reactions of 2- and 4-(5-arylpent-4-enyl)-1-cyanonaphthalenes
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Photoreactions of 1-cyanonaphthalene derivatives containing 5-arylpent-4-enyl groups at C-2 or C-4 of the naphthalene ring were investigated. Photoreactions of C-2 derivatives in benzene or CH3CN generated intramolecular [2 + 2] and [3 + 2] photocycloadducts. Substances bearing electron-rich and electron-poor phenyl groups produced respective [2 + 2] and [3 + 2] photocycloadducts preferentially. In contrast, photoreactions of C-4 linked 1-cyanonaphthalenes produced intramolecular [4 + 2] photocycloadducts as main products along with stereoisomers of tricyclic compounds as minor products. The formation of [4 + 2] photocycloadducts was promoted by using benzophenone or Michler's ketone triplet photosensitization, and quenched by O2 or ferrocene. Intramolecular singlet exciplexes, which serve as important intermediates in the mechanistic pathways for these reactions, governed the site-selectivities in photoreactions of both of the 2- and 4-(5-arylpent-4-enyl)-1-cyanonaphthalenes. In addition, [4 + 2] photocycloadducts were observed to undergo di-π-methane rearrangement under irradiation conditions to produce angular triquinane derivatives.
- Maeda, Hajime,Enya, Kouhei,Negoro, Naoki,Mizuno, Kazuhiko
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p. 173 - 184
(2019/02/15)
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- Palladium-catalyzed oxidative arylacetoxylation of alkenes: Synthesis of indole and indoline derivatives
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A method for the oxidative arylacetoxylation of alkenes has been developed to synthesize indole and indoline derivatives from readily accessible substrates. The cinnamyl tethered anilines with picolinamide as a directing group provided 3-substituted indoles via intramolecular oxidative arylacetoxylation, and the 2-methyl substituted cinnamyl anilines furnished indoline derivatives with 3-position quaternary stereocenters in good to excellent yields via sequential intramolecular oxidative arylacetoxylation, hydrolysis and oxidation steps.
- Karnakanti, Shuklachary,Zang, Zhong-Lin,Zhao, Sheng,Shao, Pan-Lin,Hu, Ping,He, Yun
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supporting information
p. 11205 - 11208
(2017/10/17)
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- Divergent Gold(I)-Catalyzed Skeletal Rearrangements of 1,7-Enynes
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The gold(I) complex catalyzed cycloisomerization and skeletal rearrangement of 1,n-enynes (n=5-7) is a powerful methodology for the efficient synthesis of complex molecular architectures. In contrast to 1,6-enynes, readily accessible homologous 1,7-enynes are largely unexplored in such transformations. Here, the divergent skeletal rearrangement of all-carbon 1,7-enynes by catalysis with a cationic gold(I) complex is reported. Depending on electronic and steric factors, differently substituted 1,7-enynes react via different carbocations formed from a common gold carbene intermediate to yield on the one hand novel exocyclic allenes and on the other hand tricyclic hexahydro-anthracenes through a novel dehydrogenative Diels-Alder reaction. Two birds with a gold-stone! Divergent gold(I) catalysis unraveled a novel cycloisomerization and a dehydrogenative Diels-Alder reaction of 1,7-enynes.
- Mei?, Rebecca,Kumar, Kamal,Waldmann, Herbert
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supporting information
p. 13526 - 13530
(2015/09/22)
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- Rhodium-Catalyzed Stereoselective Intramolecular [5 + 2] Cycloaddition of 3-Acyloxy 1,4-Enyne and Alkene
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The first rhodium-catalyzed intramolecular [5 + 2] cycloaddition of 3-acyloxy 1,4-enyne and alkene was developed. The cycloaddition is highly diastereoselective in most cases. Various cis-fused bicyclo[5.3.0]decadienes were prepared stereoselectively. The chirality in the propargylic ester starting materials could be transferred to the bicyclic products with high efficiency. Electron-deficient phosphine ligand greatly facilitated the cycloaddition. Up to three new stereogenic centers could be generated. The resulting diene in the products could be hydrolyzed to enones, which allowed the introduction of more functional groups to the seven-membered ring.
- Shu, Xing-Zhong,Schienebeck, Casi M.,Li, Xiaoxun,Zhou, Xin,Song, Wangze,Chen, Lianqing,Guzei, Ilia A.,Tang, Weiping
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supporting information
p. 5128 - 5131
(2015/11/03)
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- Multifunctional novel Diallyl disulfide (DADS) derivatives with β-amyloid-reducing, cholinergic, antioxidant and metal chelating properties for the treatment of Alzheimer's disease
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A series of novel Diallyl disulfide (DADS) derivatives were designed, synthesized and evaluated as chemical agents, which target and modulate multiple facets of Alzheimer's disease (AD). The results showed that the target compounds 5a-l and 7e-m exhibited significant anti-Aβ aggregation activity, considerable acetylcholinesterase (AChE) inhibition, high selectivity towards AChE over butyrylcholinesterase (BuChE), potential antioxidant and metal chelating activities. Specifically, compounds 7k and 7l exhibited highest potency towards self-induced Aβ aggregation (74% and 71.4%, 25 μM) and metal chelating ability. Furthermore, compounds 7k and 7l disaggregated Aβ fibrils generated by Cu2+-induced Aβ aggregation by 80.9% and 78.5%, later confirmed by transmission electron microscope (TEM) analysis. Besides, 7k and 7l had the strongest AChE inhibitory activity with IC50 values of 0.056 μM and 0.121 μM, respectively. Furthermore, molecular modelling studies showed that these compounds were capable of binding simultaneously to catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. All the target compounds displayed moderate to excellent antioxidant activity with ORAC-FL values in the range 0.546-5.86 Trolox equivalents. In addition, absorption, distribution, metabolism and excretion (ADME) profile and toxicity prediction (TOPKAT) of best compounds 7k and 7l revealed that they have drug like properties and possess very low toxic effects. Collectively, the results strongly support our assertion that these compounds could provide good templates for developing new multifunctional agents for AD treatment.
- Manral, Apra,Saini, Vikas,Meena, Poonam,Tiwari, Manisha
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p. 6389 - 6403
(2015/10/05)
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- Congested C-C bonds by Pd-catalyzed enantioselective allyl-allyl cross-coupling, a mechanism-guided solution
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Under the influence of a chiral bidentate diphosphine ligand, the Pd-catalyzed asymmetric cross-coupling of allylboron reagents and allylic electrophiles establishes 1,5-dienes with adjacent stereocenters in high regio-and stereoselectivity. A mechanistic study of the coupling utilizing reaction calorimetry and density functional theory analysis suggests that the reaction operates through an inner-sphere 3,3′-reductive elimination pathway, which is both rate-defining and stereodefining. Coupled with optimized reaction conditions, this mechanistic detail is used to expand the scope of allyl-allyl couplings to allow the generation of 1,5-dienes with tertiary centers adjacent to quaternary centers as well as a unique set of cyclic structures.
- Ardolino, Michael J.,Morken, James P.
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p. 7092 - 7100
(2014/06/09)
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- Catalytic enantioselective allyl-allyl cross-coupling with a borylated allylboronate
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Catalytic enantioselective allyl-allyl cross-coupling of a borylated allylboronate reagent gives versatile borylated chiral 1,5-hexadienes. These compounds may be manipulated in a number of useful ways to give functionalized chiral building blocks for asymmetric synthesis.
- Le, Hai,Kyne, Robert E.,Brozek, Laura A.,Morken, James P.
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p. 1432 - 1435
(2013/07/05)
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- One-pot synthesis of functionalized p-terphenyl derivatives
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A one-pot synthetic route for preparing functionalized p-terphenyl derivatives 1 and 4 is developed. The route is easily carried from the treatment of cinnamyl aldehydes 2 with substituted allylsulfones 3 in good yields via the tandem intermolecular aldol condensation/intramolecular electrocyclization/ oxidative dehydrogenation.
- Chang, Meng-Yang,Chan, Chieh-Kai,Wu, Ming-Hao
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p. 7916 - 7924
(2013/08/23)
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- On the stereoselective bicyclization of aminodienes catalyzed by chelating diamide complexes of the group 3 metals. A direct comparison of Sc(iii) and Y(iii) bis(amide)s with an application to the synthesis of alkaloid 195F
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Highly diastereoselective bicyclizations of aminodienes catalyzed by chelating diamide complexes of Sc(iii) and Y(iii) that lead to pyrrolizidines and indolizidines are described. This bis(annulation) procedure has been utilized in a concise synthesis of the pyrrolizidine alkaloid 195F.
- Jiang, Tao,Livinghouse, Tom,Lovick, Helena M.
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supporting information; experimental part
p. 12861 - 12863
(2012/02/02)
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- Diastereocontrol in asymmetric allyl-allyl cross-coupling: Stereocontrolled reaction of prochiral allylboronates with prochiral allyl chlorides
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Palladium-catalyzed allyl-allyl cross-coupling was investigated with substituted prochiral allylic boronates. These reactions deliver products bearing adjacent stereocenters, and the issue of diastereocontrol is therefore paramount. Under appropriately mo
- Brozek, Laura A.,Ardolino, Michael J.,Morken, James P.
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p. 16778 - 16781
(2011/12/04)
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- Enantioselective copper-catalysed allylic alkylation of cinnamyl chlorides by Grignard reagents using chiral phosphine-phosphite ligands
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The copper(I)-catalysed SN2'-type allylic substitution of E-3-aryl-allyl chlorides (cinnamyl chlorides) using Grignard reagents represents a powerful method for the synthesis of compounds carrying a benzylic stereocentre. By screening a small library of modular chiral phosphine-phosphite ligands a new copper(I)-based catalyst system was identified which allows the performance of such reactions with exceptional high degrees of regio- and enantioselectivity. Best results were obtained using TADDOLderived ligands (3 mol%), copper(I) bromide?dimethyl sulfide (CuBr?SMe2) (2.5 mol%) and methyl tert-butyl ether (MTBE) as a solvent. Various (1- alkyl-allyl)benzene derivatives were prepared with up to 99% ee (GC) in isolated yields of up to 99%. In most cases the product contained less than 3% of the linear regioisomer (except for ortho-substituted substrates). Both electron-rich and electron-deficient cinnamyl chlorides were successfully employed. The absolute configuration of the products was assigned by comparison of experimental and calculated CD spectra. The substrates were prepared from the corresponding alcohols by reaction with thionyl chloride. Initially formed mixtures of regioisomeric allylic chlorides were homogenised by treatment with CuBr?SMe2 (2.5 mol%) in the presence of triphenyl phosphine (PPh3) (3 mol%) in MTBE at low temperature to give the pure linear isomers. In reactions with methylmagnesium bromide (MeMgBr) an ortho-diphenylphosphanyl-arylphosphite ligand with an additional phenyl substituent in ortho'-position at the aryl backbone proved to be superior. In contrast, best results were obtained in the case of higher alkyl Grignard reagents (such as ethyl-, n-butyl-, isopropyl-, and 3-butenylmagnesium bromides) with a related ligand carrying an isopropyl substituent in ortho'-position. The method was tested on a multimmol scale and is suited for application in natural product synthesis.
- Loelsberg, Wibke,Ye, Shute,Schmalz, Hans-Guenther
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supporting information; experimental part
p. 2023 - 2031
(2010/10/21)
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- Expedient access to branched allylic silanes by copper-catalysed allylic substitution of linear allylic halides
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An unprecedented copper-catalysed allylic transposition enables the regioselective synthesis of branched allylic silanes from linear allylic halides through direct C-Si bond formation.
- Vyas, Devendra J.,Oestreich, Martin
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supporting information; experimental part
p. 568 - 570
(2010/05/01)
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- Catalytic SN2′-selective substitution of allylic chlorides with arylboronic esters
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(Figure Presented) A copper-catalyzed SN2′-selective arylation of allylic chlorides has been achieved using arylboronic esters as nucleophiles. Arylation products were obtained in high yield with a variety of allylic chlorides and arylboronic e
- Whittaker, Aaron M.,Rucker, Richard P.,Lalic, Gojko
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supporting information; experimental part
p. 3216 - 3218
(2010/10/02)
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- Ruthenium-catalyzed synthesis of allylic alcohols: Boronic acid as a hydroxide source
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Secondary allylic alcohols were synthesized from linear allylic halides or carbonates using a catalytic amount of a ruthenium complex in the presence of boronic acid. The effects of solvent, base, ruthenium precursor, and boronic acid were fully explored, and the scope of the reaction was extended to various sub-strates. We also describe a preliminary investigation towards an enantioselective process.
- Bouziane, Asmae,Helou, Marion,Carboni, Bertrand,Carreaux, Francois,Demerseman, Bernard,Bruneau, Christian,Renaud, Jean-Luc
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experimental part
p. 5630 - 5637
(2009/05/27)
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- Design, synthesis, and structure-activity relationships of haloenol lactones: Site-directed and isozyme-selective glutathione S-transferase inhibitors
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Overexpression of glutathione S-transferase (GST), particularly the GST-π isozyme, has been proposed to be one of the biochemical mechanisms responsible for drug resistance in cancer chemotherapy, and inhibition of overexpressed GST has been suggested as an approach to combat GST-induced drug resistance. 3-Cinnamyl-5(E)-bromomethylidenetetrahydro-2-furanone (1a), a lead compound of site-directed GST-π inactivator, has been shown to potentiate the cytotoxic effect of cisplatin on tumor cells. As an initial step to develop more potent and more selective haloenol lactone inactivators of GST-π, we examined the relationship between the chemical structures of haloenol lactone derivatives and their GST inhibitory activity. A total of 16 haloenol lactone derivatives were synthesized to probe the effects of (1) halogen electronegativity, (2) electron density of aromatic rings, (3) molecular size and rigidity, (4) lipophilicity, and (5) aromaticity on the potency of GST-π inactivation. The inhibitory potency of each compound was determined by time-dependent inhibition tests, and recombinant human GST-π was used to determine their inhibitory activity. Our structure-activity relationship studies demonstrated that (1) reactivity of the halide leaving group plays a weak role in GST inactivation by the haloenol lactones, (2) aromatic electron density may have some influence on the potency of GST inactivation, (3) high rigidity likely disfavors enzyme inhibition, (4) lipophilicity is inversely proportional to enzyme inactivation, and (5) an unsaturated system may be important for enzyme inhibition. This work facilitated understanding of the interaction of GST-π with haloenol lactone derivatives as site-directed and isozyme-selective inactivators, possibly potentiating cancer chemotherapy.
- Wu, Zhixing,Minhas, Gurpreet Singh,Wen, Dingyi,Jiang, Hualiang,Chen, Kaixian,Zimniak, Piotr,Zheng, Jiang
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p. 3282 - 3294
(2007/10/03)
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- SPIROINDOLINEPIPERIDINE DERIVATIVES
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Insecticidal, acaricidal, nematicidal or molluscicidal compounds of formula (I) wherein Y is a single bond, C=O, C=S or C=(O)q where q is 0, 1 or 2; and R1, R2, R3, R4, R8, R9 an
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- Pyrazolopyrimidine Ribonucleosides as Anticoccidials. 3. Synthesis and Activity of Some Nucleosides of 4-pyrazolopyrimidines
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Ribonucleosides of 4-(alkylthio)-1H-pyrazolopyrimidines have been shown to be useful anticoccidial agents .In that study, the unsaturated 4-allylthio and 4-crotylthio derivatives (19 and 20) were shown to be more active in vivo against Eimeria tenella than their saturated congeners; therefore, some unsaturated (arylalkyl)thio derivatives were synthesized and investigated as anticoccidial agents.The novel compounds in this study (2 to 18) were prepared by the alkylation of 4-mercapto-1-β-D-ribofuranosyl-1H-pyrazolopyrimidine (1), which was prepared by an enzymatic method.The (E)-4-cinnamylthio derivative (2) and the 5'-monophosphate (18) were the most active compounds against E. tenella in vivo.None of the analogues with substituents in the aryl moiety (3 to 13) was more active than 2 in vivo.The geometry about the double bond was important, since the (Z)-4-cinnamylthio derivative (14) was inactive both in vitro and in vivo.The 4-(3-phenylpropynyl)thio and 4-(5-phenyl-2,4-pentadienyl)thio derivatives (15 and 16) were at least as active as 2 in vitro; however, they were less active than 2 in vivo.Compound 2 was effective in vivo against E. tenella, E. necatrix, E. maxima, and E. brunetti; these species of Eimeria were controlled when 2 was given in the diet at levels up to 100 ppm.Infections in vivo due to E. acervulina were controlled by 2 only at about 800 ppm.The broad spectrum of anticoccidial activity shown by 2 represents a significant improvement over the activities reported for related compounds .
- Rideout, Janet L.,Krenitsky, Thomas A.,Chao, Esther Y.,Elion, Gertrude B.,Williams, Raymond B.,Latter, Victoria S.
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p. 1489 - 1494
(2007/10/02)
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- 5,6-Benzoisoindolines
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4-Phenyl-9,9a-dihydro-5,6-benzoisoindolines, e.g. those of the formula STR1 OR SALTS THEREOF ARE ANTIASTHMATIC AND ANTIALLERGIC AGENTS.
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- Antiasthmatic 5,6-benzoisoindoline compositions
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4-Phenyl-9,9a-dihydro-5,6-benzoisoindolines, e.g. those of the formula SPC1 R = h, alkyl, alkenyl or (hydroxy or amino)-alkyl, R" = h, alkyl, OH, alkanoyloxy, alkoxy, 1/2 alkylenedioxy, benzyloxy, halogeno, CF3, NO2 or amino m,n = 1 to 4 Or salts thereof are also antiallergic agents.
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- Investigations on the question of multiple mechanisms in the cope rearrangement
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The possible occurrence of the ionic Cope rearrangement, and other non-concerted mechanisms is discussed. The synthesis of 2 - (1 - ethyl - 1 - propenyl) -2- (3 - p - methoxyphenylallyl)malononitrile (1b) and its clean thermal 1,3 rearrangement to (1 - et
- Wigfield,Feiner,Malbacho,Taymaz
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p. 2949 - 2959
(2007/10/12)
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