- A study about the synthesis of seven-membered-ring analogues of ketamine
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Synthesis of seven-membered ring analogues of ketamine was studied with two strategies. In the first approach a sequence of five reactions was used which previously applied for ketamine synthesis. This strategy led to formation of 1-[(2-chlorophenyl)(methylimino)methyl]cyclohexan-1-ol as a precursor for the target molecule. In the second approach, we have designed and attempted to synthesize a new analogue of ketamine applying challenging reactions such as ring expansion and selective bromination. The result of this route is synthesis of some interesting compounds such as 6-phenyl-1-oxa-4-thiaspiro[4.6]undecane, 3-bromo-6-phenyl-1-oxa-4-thiaspiro[4.6]undecane and 2,7-dibromo-2-phenylcycloheptanone.
- Moghimi, Abolghasem,Shahdadi, Mohammad Reza,Keshipour, Sajjad,Sadeghzadeh, Morteza
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- Catalytic Redox Chain Ring Opening of Lactones with Quinones to Synthesize Quinone-Containing Carboxylic Acids
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Catalytic ring opening of five- to eight-membered lactones with quinones is achieved through a redox chain mechanism. With low loading of a simple metal triflate Lewis acid catalyst and a chain initiator, C-H bonds of many quinones were efficiently functionalized with carboxylic acid-containing side chains. This method also features 100% atom economy and wide substrate scope. A novel route to the anti-asthma drug Seratrodast was developed. Mechanism study suggests that the redox chain reaction likely undergoes a carbocation intermediate.
- Xu, Xiao-Long,Li, Zhi
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p. 5078 - 5081
(2019/09/03)
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- Enantioselective Protonation of Silyl Enol Ethers Catalyzed by a Chiral Pentacarboxycyclopentadiene-Based Bronsted Acid
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The enantioselective protonation of silyl enol ethers was realized in the presence of a pentacarboxycyclopenta-1,3-diene-based chiral Bronsted acid catalyst with water as an achiral proton source to give the corresponding α-aryl ketones in good yields and up to 75percent ee.
- An, Shaoyu,Li, Jun,Li, Pingfan,Yuan, Chao
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supporting information
p. 1317 - 1320
(2019/06/19)
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- Synthesis of α-Arylated Cycloalkanones from Congested Trisubstituted Spiro-epoxides: Application of the House-Meinwald Rearrangement for Ring Expansion
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A three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β,β'-disubstituted benzylidene cycloalkanes (styrenes) using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Furthermore, an epoxidation followed by the House-Meinwald rearrangement (HMR) of spiro-epoxides is reported to produce a number of α-arylated cycloalkanones upon ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), with yields ranging from 15% to 95%, thus demonstrating the difficulty of achieving ring enlargement for electron-deficient spiro-epoxides. On the other hand, by means of catalysis with aluminum trichloride, the rearrangement of spiro-epoxides proceeded typically in high yields and with remarkable regioselectivity on a broader substrate scope. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enable the method to be successfully extended to some chemospecific arene shifts and the synthesis of aldehydes bearing a α-quaternary carbon. While the HMR has been extensively studied for smaller ring enlargement, we are pleased to report herein that larger cyclohexanones and cycloheptanones can be obtained efficiently from more sterically demanding trisubstituted spiro-epoxides bearing electron-releasing and electron-neutral arene substituents.
- Jeedimalla, Nagalakshmi,Jacquet, Camille,Bahneva, Diana,Youte Tendoung, Jean-Jacques,Roche, Stéphane P.
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p. 12357 - 12373
(2018/09/06)
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- Fe-catalyzed regiodivergent [1,2]-shift of α-aryl aldehydes
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An Fe-catalyzed conversion of aldehydes to ketones via [1,2]-shift has been developed. This skeletal rearrangement shows a wide substrate scope and chemoselectivity profile while exhibiting an excellent [1,2]-aryl or [1,2]-alkyl shift selectivity that is easily switched by electronic effects.
- Gutierrez-Bonet, Alvaro,Flores-Gaspar, Areli,Martin, Ruben
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supporting information
p. 12576 - 12579
(2013/09/23)
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- New methylene homologation method for cyclic ketones
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Teaching new tricks to an old dog: By intercepting adducts between ketones and lithium trimethylsilyldiazomethane, a new Tiffeneau-Demjanov type methylene homologation could be realized in a single-step operation. Among proton sources and Lewis acids, silica gel was found to be the most effective reagent for the protonation of intermediates and their subsequent ring expansion (see scheme). Copyright
- Liu, Huaqing,Sun, Chunrui,Lee, Nam-Kyu,Henry, Roger F.,Lee, Daesung
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supporting information
p. 11889 - 11893
(2012/10/29)
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- Highly efficient and enantioselective α-arylation of cycloalkanones by scandium-catalyzed diazoalkane-carbonyl homologation
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Functionalized α-tertiary and -quaternary 2-arylcycloalkanones are rapidly accessed by scandium(III) triflate-catalyzed diazo-alkane-carbonyl homologations. Recent developments have allowed for carbon insertion reactions to be performed with catalyst loadings as low as 0.5 mol% on scales up to 5 mmol. Pairing readily available bis- and tris(oxazoline) based ligands with scandium triflate allows access to arylated medium ring carbocycles with enantioselectivities up to 98:2 er and >98% yield. The formal C-C insertion of aryldiazo-methanes into unsubstituted cycloalkanones provides a single-step solution to the ongoing challenge of α-arylation. Georg Thieme Verlag Stuttgart · New York.
- Rendina, Victor L.,Kaplan, Hilan Z.,Kingsbury, Jason S.
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experimental part
p. 686 - 693
(2012/04/04)
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- One-pot method for α-phenylation of ketones using isoxazolidine and triphenylaluminum
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The efficient one-pot umpolung α-phenylation of ketones via N-alkenylisoxazolidine is described. When the various ketones are treated with triphenylaluminum prepared from phenylmagnesium chloride and AlCl3 in the presence of isoxazolidine, the desired products are obtained in good to moderate yield. This method is equivalent to a direct α-arylation reaction of carbonyl groups.
- Miyoshi, Tetsuya,Sato, Shohei,Tanaka, Hiroya,Hasegawa, Chihiro,Ueda, Masafumi,Miyata, Okiko
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experimental part
p. 4188 - 4191
(2012/08/28)
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- An enantioselective synthesis of 2-aryl cycloalkanones by sc-catalyzed carbon insertion
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Current methods for asymmetric α-arylation require blocking groups to prevent reaction at the R0-carbon, basic conditions that promote racemization, or multistep synthesis. This work records the first catalytic enantioselective examples of the diazoalkane-carbonyl homologation reaction. Medium ring 2-aryl ketones are prepared in one step in up to 98:2 er and 99% yield from the unsubstituted lower homologue by Sc-catalyzed aryldiazomethyl insertion with simple bis- and tris(oxazoline) ligands.
- Rendina, Victor L.,Moebius, David C.,Kingsbury, Jason S.
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supporting information; experimental part
p. 2004 - 2007
(2011/07/07)
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- Aryl(chloro)methyl 4-tolyl sulfoxides: Synthesis and application to the synthesis of α-aryl ketones
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Aryl(chloro)methyl 4-tolyl sulfoxides were synthesized from arylmethyl 4-tolyl sulfoxides in moderate-to-good yields by sequential treatment with lithium diisopropylamide and tosyl chloride at low temperatures. Treatment of the lithium α-sulfinyl carbanion of the aryl(chloro)methyl 4-tolyl sulfoxides with aldehydes or ketones resulted in the formation of adducts in good-to-high yields. Treatment of these adducts with tert-butylmagnesium chloride gave the corresponding magnesium alkoxides. On treatment with isopropylmagnesium chloride, the alkoxides gave the corresponding magnesium β-oxido carbenoids, which rearranged to give α-aryl ketones in good-to-high yields. The magnesium enolate intermediates generated by rearrangement of the -oxido carbenoids could also be trapped with electrophiles to give α-aryl α-substituted ketones. These procedures offer a good method for the synthesis of a variety of α-aryl ketones from aldehydes and ketones. Georg Thieme Verlag Stuttgart. New York.
- Fukuda, Shigehiko,Tsuji, Kazuhito,Musashi, Jun,Nonaka, Ryo,Kimura, Tsutomu,Satoh, Tsuyoshi
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p. 3615 - 3626
(2011/12/16)
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- Chiral sulfinamide/achiral sulfonic acid cocatalyzed enantioselective protonation of enol silanes
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The application of chiral sulfinamides and achiral sulfonic acids as a cocatalyst system for enantioselective protonation reactions is described. Structurally simple, easily accessible sulfinamides were found to induce moderate-to-high ee's in the formation of 2-aryl-substituted cycloalkanones from the corresponding trimethylsilyl enol ethers.
- Beck, Elizabeth M.,Hyde, Alan M.,Jacobsen, Eric N.
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supporting information; experimental part
p. 4260 - 4263
(2011/10/08)
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- Highly enantioselective organocatalytic oxidative kinetic resolution of secondary alcohols using chirally Modified AZADOs
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A highly enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols has been accomplished using asymmetric organocatalysis. A panel of chirally modified 2-azaadamantane N-oxyls (AZADOs) exhibit superior catalytic act
- Tomizawa, Masaki,Shibuya, Masatoshi,Iwabuchi, Yoshiharu
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supporting information; experimental part
p. 1828 - 1831
(2009/09/06)
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- Et2Zn-mediated rearrangement of bromohydrins
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(Chemical Equation Presented) A simple and highly efficient method for the rearrangement of bromohydrins mediated by Et2Zn to synthesize carbonyl compounds was described. Various β-bromo alcohols were treated with 0.6 equiv of Et2Zn to form a zinc complex in CH 2Cl2 at room temperature for 2 h, followed by 1,2-migration to give the corresponding carbonyl compounds. This remarkable and clean rearrangement is general for acyclic and cyclic bromohydrins, and a variety of ring-expansive and -contractive carbonyl compounds were obtained in good to excellent yields according to the feature of the starting bromohydrins. The functional group tolerance of organozinc reagents in this reaction will be useful in organic synthesis. The scope and limitations of this rearrangement process were also investigated.
- Li, Lezhen,Cai, Peijie,Guo, Qingxiang,Xue, Song
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p. 3516 - 3522
(2008/09/20)
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- Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors
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Screening of the Roche compound library led to the identification of cis-N-(2-phenyl-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform.
- Pinard, Emmanuel,Ceccarelli, Simona M.,Stalder, Henri,Alberati, Daniela
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p. 349 - 353
(2007/10/03)
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- The design and synthesis of 9-phenylcyclohepta[d]pyrimidine-2,4-dione derivatives as potent non-nucleoside inhibitors of HIV reverse transcriptase
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Novel compounds, which can be considered as conformationally restricted analogues of MKC-442, have been synthesized and tested as inhibitors of the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1). Reaction of urea with a β-ketoester furnished 6,7,8,9-tetrahydro-9-phenyl-1H- cyclohepta[d]pyrimidine-2,4-(3H,5H)-dione (6a) and 6,7,8,9-tetrahydro-9-p-tolyl- 1H-cyclohepta[d]pyrimidine-2,4-(3H,5H)-dione (6b) which were then alkylated at the N-1 position with chloromethyl ether, allyl bromide and benzyl bromide to afford the target compounds 7a-b, 8a-b, 9 and 10, respectively. The seven-membered, annelated compounds have a relatively rigid structures and can lock the orientation of the aromatic ring. Chemical modification at N-1 of the pyrinidine ring and the 9-phenyl ring was attempted, with the aim of improving the antiretroviral activity. In particular, replacement of the aliphatic group with the phenyl moiety at the terminus of N-1 side chain can enhance the activity. The most active compounds showed activity in the low micromolar range with IC50 values comparable to that of nevirapine. The biological activity results are in accordance with the docking results. The Royal Society of Chemistry 2006.
- Wang, Xiaowei,Lou, Qinghua,Guo, Ying,Xu, Yang,Zhang, Zhili,Liu, Junyi
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p. 3252 - 3258
(2008/03/13)
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- GaCl3-catalyzed skeletal rearrangement of α,α, α-trisubstituted aldehydes
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(Chemical Equation Presented) GaCl3 is found to be a superior catalyst for the skeletal rearrangement of α,α,α- trisubstituted aldehydes to ketones. The rearrangement can proceed smoothly in the presence of a catalytic amount of GaCl3, and even substrates having no heteroatoms α to the carbonyl group or without steric strains can be used. Double activation of a carbonyl group by two molecules of GaCl 3 was supported on the basis of experimental data and a DFT study.
- Oshita, Masayuki,Okazaki, Takao,Ohe, Kouichi,Chatani, Naoto
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p. 331 - 334
(2007/10/03)
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- Oxidative rearrangements of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol: A general, regiospecific synthesis of α-aryl ketones
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The treatment of arylalkenes with [hydroxy(tosyloxy)iodo]benzene in 95% methanol affords the corresponding α-aryl ketones. This oxidative rearrangement is general for acyclic and cyclic arylalkenes and permits regioselective syntheses of isomeric α-phenyl ketone pairs.
- Justik, Michael W.,Koser, Gerald F.
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p. 6159 - 6163
(2007/10/03)
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- Regioselectivity of the Base-Induced Ring Cleavage of 1-Oxygenated Derivatives of Cyclobutabenzene
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Oxy anions 3 generated from 1,2-dihydrocyclobutabenzen-1-ones 1 through addition of a charged nucleophile or from 1-hydroxy-1,2-dihydrocyclobutabenzenes 2 by deprotonation with base lead to stable products through distal and/or proximal cleavage of the strained four-membered ring via benzyl carbanion 4 and/or aryl carbanion 5. A systematic study of this process reveals the relative stability of the two isomeric carbanions 4 and 5 as a key factor in determining the course of the ring-cleavage reaction. While benzyl carbanions 4 can be trapped with carbon electrophiles, attempts at trapping aryl carbanions 5 with electrophiles other than H+ failed. In protic solvents, the magnesium salt of the tertiary alcohol 2 shows an increased rate of proximal cleavage as compared to its alkali salts. From this, we conclude that, in contrast to benzyl carbanions 4, free aryl carbanions 5 are of transient existence only. Proximal C,C-bond cleavage seems to occur either through protonation of 5 from a fast, reversible equilibrium 3?5 in which 3 strongly predominates, or in protic solvents possibly even through a rate-limiting protonation of 3 at the aromatic C-atom, bypassing free anion 5 altogether. Thus, additional factors other than just the relative stability of isomeric carbanions 4 and 5 are of importance in determining the regiochemistry of the base-induced C,C-bond cleavage in ketones 1 and in alcohols 2.
- Gokhale, Abha,Schiess, Peter
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p. 251 - 267
(2007/10/03)
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- Direct α-arylation of ketones: The reaction of cyclic ketone enolates with diphenyliodonium triflate
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Diphenyliodonium triflate 1a reacts with the lithium enolates of cyclic ketones 2 (ring size = 5 - 8), in the presence of stoichiometric quantities of copper cyanide, to afford the corresponding α-phenylated ketones 3 or α,α'-diphenylated ketones 4.
- Ryan, John H.,Stang, Peter J.
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p. 5061 - 5064
(2007/10/03)
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- Electrooxidative pinacol-type rearrangement of β-hydroxy sulfides. Efficient C-S cleavage mediated by chloride ion oxidation
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Electrooxidation of α-phenyl substituted β-hydroxy sulfides in dichloromethane in the presence of chloride ions as the electrolyte results in a novel pinacol-type rearrangement to give 2-phenyl substituted ketones like 2-phenylcycloalkanone as the ring expansion product. The rearrangement is induced by an electrogenerated chloronium ion, which effects, instead of common C-C scission, a selective C-S cleavage of β-hydroxy sulfides.
- Kimura, Makoto,Kobayashi, Kazutaka,Yamamoto, Yasushi,Sawaki, Yasuhiko
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p. 4303 - 4310
(2007/10/03)
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- Ring size effect in oxidation of 1-phenylcycloalkenes with chromic anhydride-pyridine complex: Preferential formation of epoxide with increase in ring size
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A marked ring size effect in the oxidation of 1-phenylcycloalkenes (1) with chromic anhydride-pyridine complex has been observed.While 1-phenylcyclopentene (1a) and 1-phenylcyclohexene (1b) give the expected α,β-unsaturated cyclic ketones (2a,b) 1-phenylcycloheptene (1c) and 1-phenylcyclooctene (1d) furnish epoxides (5c,d) as the major products.
- Singh, Chandan,Saxena, Gunjan
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p. 1176 - 1177
(2007/10/02)
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- Reactions of O,O-Diprotonated Nitro Olefins with Benzenes. Formations of Phenylacetones, 4H-1,2-Benzoxazines and Biarylacetone Oximes
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O,O-Diprotonated nitro olefins undergo three alternative electrophilic reactions which yield α-phenylacetones, 4H-1,2-benzoxazines and biphenylacetone oximes depending on the reaction conditions (temperature and time) and aromatic substrates.Although these reactions are seemingly divergent, a common intermediate of a phenylated protonated aci-nitro species, derived from the dication, is postulated to be involved in the reactions.Furthermore, the formation of benzoxazines and biphenylacetone oximes can be interpreted in terms of participation of novel chemical species with phenylethylene dication character derived from the common intermediate.
- Ohwada, Tomohiko,Okabe, Kazuaki,Ohta, Toshiharu,Shudo, Koichi
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p. 7539 - 7555
(2007/10/02)
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- REACTION OF α,β-UNSATURATED ALDEHYDES WITH HYDROGEN PEROXIDE CATALYSED BY BENZENESELENINIC ACIDS AND THEIR PRECURSORS
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Oxidation of α,β-unsaturated aldehydes with hydrogen perixide catalysed by benzeneselenic acids and their precursors has been investigated.Bis 2-nitrophenyl diselenide has proved to be the most effective catalyst.The major products resulting from the oxidation are vinyl formates (a) which on hydrolysis give saturated aldehydes or ketones (g) having the carbon chain shortened by one carbon atom, compared with the starting aldehydes.The minor products are formyloxyoxiranes (b), α-hydroxycarbonyl (e) and α-formyloxycarbonyl (f) compounds with the carbon chain shortened by one carbon atom.Carbonyl compounds d, formally derived from an oxidative fission of the carbon-carbon double bond, have been also isolated.Diformyloxy (4c) and formyloxyacetoxy phenylmethane (5c) have been isolated when cinnamaldehyde (4) or 1-phenyl-2-formyloxypropane (5a) were oxidized, respectively.Possible mechanisms of formation of these products are discussed.Similar products resulted when α,β-unsaturated aldehydes were oxidized with organic peroxy acids.
- Syper, Ludwik
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p. 2853 - 2872
(2007/10/02)
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- Ring Contraction of 2-Chlorocyclohexanone with Grignard Reagents
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The reaction of 2-chlorocyclohexanone with phenylmagnesium bromide in refluxing tetrahydrofuran unexpectedly afforded the ring-contracted product, cyclopentyl phenyl ketone, as the main product in moderate yield.The reactivities of several cyclic 2-haloketones were examined.Keywords - 2-chlorocyclohexanone; Grignard reaction; ring contraction; cyclopentyl phenyl ketone; solvent effect; THF; conformational isomer
- Hori, Mikio,Kataoka, Tadashi,Shimizu, Hiroshi,Imai, Eiji,Iwamura, Tatsunori,Maeda, Kaori
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p. 3599 - 3605
(2007/10/02)
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