- Synthesis of Polysubstituted Meta-Halophenols by Anion-Accelerated 2π-Electrocyclic Ring Opening
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Disrotatory – thermally allowed – 2π-electrocyclic ring-opening reactions require high temperatures to proceed. Herein, we report the first anion-accelerated 2π-electrocyclic ring opening of 6,6-dihalobicyclo[3.1.0]hexan-2-ones at low temperature to give the corresponding meta-halophenols in good to high yields (18 examples, 29–92 % yield, average: 65 %). Many of the phenols have unconventional substitution patterns and are reported here for the first time. Furthermore, the strength of the methodology was shown by the total synthesis of the densely functionalized phenolic natural product caramboxin (isolated as the lactam dehydrate). The reaction mechanism underlying the anion-acceleration was investigated in an ab initio study, which concluded that base-mediated proton abstraction anti to the concurrently departing endo-bromine was the initiating step in an overall concerted reaction mechanism leading directly to the meta-halophenol.
- Staudt, Markus,S?lling, Theis,Bunch, Lennart
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supporting information
p. 10941 - 10947
(2021/06/16)
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- Reductive Aromatization of Quinols with B2pin2 as Deoxidizing Agent
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We have demonstrated B2pin2 as superior deoxidizing agent for the reductive deoxygenation of quinol derivatives under basic conditions. A wide range of highly functionalized phenols were obtained in good yields including a complex drug molecule, which revealed the high functional group tolerance of this protocol.
- Liu, Bin,Xu, Yin,Luo, Zhibin,Xie, Jimin
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supporting information
p. 1022 - 1024
(2020/03/19)
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- Magnolol dimer-derived fragments as PPARγ-selective probes
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Partial agonists of the transcription factor PPARγ (peroxisome proliferator-activated receptor γ) have shown potential for the treatment of metabolic and inflammatory conditions and novel activators serve as valuable tool and lead compounds. Based on the
- Dreier, Dominik,Resetar, Mirta,Temml, Veronika,Rycek, Lukas,Kratena, Nicolas,Schnürch, Michael,Schuster, Daniela,Dirsch, Verena M.,Mihovilovic, Marko D.
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p. 7019 - 7028
(2018/10/17)
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- Examination of Selectivity in the Oxidation of ortho- and meta-Disubstituted Benzenes by CYP102A1 (P450 Bm3) Variants
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Cytochrome P450 CYP102A1 (P450 Bm3) variants were used to investigate the products arising from the P450 catalysed oxidation of a range of disubstituted benzenes. The variants used all generated increased levels of metabolites compared to the wild-type enzyme. With ortho-halotoluenes up to six different metabolites could be identified whereas the oxidation of 2-methoxytoluene generated only two aromatic oxidation products. Addition of an ethyl group markedly shifted the selectivity for oxidation to the more reactive benzylic position. Epoxidation of an alkene was also preferred to aromatic oxidation in 2-methylstyrene. Significant minor products arising from the migration of one substituent to a different position on the benzene ring were formed during certain P450-catalysed substrate turnovers. For example, 2-bromo-6-methylphenol was formed from the turnover of 2-bromotoluene and the dearomatisation product 6-ethyl-6-methylcyclohex-2,4-dienone was generated from the oxidation of 2-ethyltoluene. The RLYF/A330P variant altered the product distribution enabling the generation of certain metabolites in higher quantities. Using this variant produced 4-methyl-2-ethylphenol from 3-ethyltoluene with ≥90 % selectivity and with a biocatalytic activity suitable for scale-up of the reaction.
- Munday, Samuel D.,Dezvarei, Shaghayegh,Lau, Ian C.-K.,Bell, Stephen G.
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p. 2512 - 2522
(2017/07/12)
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- Explorations of the solubilizing effectiveness of CH3OCH2CH2O substituents in the photocyclizations of some 1,2-diarylethylenes to [n]phenacenes
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We have previously published many photocyclizations of 1,2-diarylethylenes to produce zig-zag aromatic ring systems with n = 5, 7, and 11 fused benzene rings. We invented the name [n]phenacenes for these compounds. To increase their solubilities we attach
- Bohen, Alyssa A.,Mullane, Kimberly C.,Bohen, Joseph M.,Mallory, Clelia W.,Mallory, Frank B.
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p. 3342 - 3345
(2015/03/18)
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- 9-AZABICYCLO [3 . 3 . 1] NONANE DERIVATIVES AS MONOAMINE REUPTAKE INHIBITORS
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The present invention relates to a 9-azabicyclo[3.3.1]nonane derivative of formula (I), wherein R1 is H or C1-5alkyl; X is O or NR2, wherein R2 is H, C1-5alkyl or C2-5acyl and Ar is C6-10aryl or a 5-10 membered heteroaryl ring system, both being optionally substituted with one to three of R3-R5 independently selected from halogen, C1-5alkyl, C1-5alkoxy, C3-6cycloalkyl, C2-5alkenyl, C2-5alkynyl, CN, NO2, hydroxy, phenyl, phenoxy and phenylC1-2alkoxy, wherein said C1-5alkyl and C1-5alkoxy are optionally substituted with one to three halogens and wherein said phenyl, phenoxy and phenylC1-2alkoxy are optionally substituted with one to three substituents independently selected from halogen and methyl or two of R3-R5 at adjacent positions together form a methylenedioxy or propylene unit, with the proviso that the compounds exo-9-methyl-3-phenoxy-9-azabicyclo[3.3.1]nonane and N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H indazole-5-amine are excluded, or a pharmaceutically acceptable salt or solvate thereof. The invention also relates to pharmaceutical compositions comprising said 9-azabicyclo[3.3.1]nonane derivatives and to their use in therapy.
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Page/Page column 24
(2010/11/26)
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- Electronic effects of ring substituents on triplet benzylic biradicals
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UV irradiation of α-(o-alkylphenyl)acetophenones with a methoxy or cyano substituent para to the o-alkyl group of the α-aryl ring has revealed that a methoxy group slightly increases the stereoselectivity but not the quantum yield of indanol formation, whereas a cyano group greatly lowers both diastereoselectivity and quantum efficiency, confirming the likelihood that hydrogen-bonding of the hydroxy group to the α-phenyl ring plays an important role in the cyclization of the photogenerated triplet 1,5-biradical intermediates.
- Wagner, Peter J.,Wang, Lingling
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p. 645 - 647
(2007/10/03)
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- Vitamin D analogues
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The present invention relates to novel triaromatic compounds having the general formula (I): as well as to a method for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine (in dermatology, in car
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Page column 22
(2010/02/09)
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- Triaromatic vitamin D analogues
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The invention relates, as novel and useful industrial products, to triaromatic compounds, which are vitamin D analogues, of general formula (I): and also to a method for preparing them and to their use in pharmaceutical compositions intended for use in human or veterinary medicine, or alternatively in cosmetic compositions.
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- Substituted acid derivatives useful as antidiabetic and antiobesity agents and method
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Compounds are provided which have the structure wherein Q is C or N, A is 0 or S, Z is O or a bond, X is CH or N and R1, R2, R2a, R2b, R2c, R3, Y, x, m, and n are as defined herein, which compounds are useful as antidiabetic, hypolipidemic, and antiobesity agents.
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- Some evidence in favour of an electron transfer mechanism in the TiO2 photosensitized oxidation of benzyl derivatives in aqueous media
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The structure and/or distribution of products from the TiO2-sensitized photooxidation of some benzyl derivatives in aerated and/or deaerated aqueous media and in the presence of Ag2SO4 are reported. The results suggest that the single electron transfer process from the substrate to the photogenerated hole, previously proposed in CH3CN, should also be operative on gradually going from aqueous CH3CN to pure water.
- Ranchella, Michele,Rol, Cesare,Sebastiani, Giovanni V.
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p. 311 - 315
(2007/10/03)
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- ipso Halogenation. II. Bromination of phenols, isomerisation and disproportionation of bromophenols, and dione-phenol rearrangement of bromodienones
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Bromination of p-cresol, bromo-p-cresol, 3,4-dimethylphenol, and mesitol in trifluoromethanesulfonic acid gices as the main product the bromo derivative with bromine meta to hydroxyl, a result attributed to the intermediate formation of a bromodienone and its rearrangement.Phenols does not give m-bromophenol in trifluoromethanesulfonic acid. 4-Bromo-2,4,6-trimethylcyclohexa-2,5-dienone rearranges to 3-bromomesitol in trifluoromethanesulfonic acid and, similarly, 2,4,6-tribromo-4-methylcyclohexa-2,5-dienone rearranges to 3-bromomesitol in trifluoromethanesulfonic acid and, similarly, 2,4,6-tribromo-4-methylcyclohexa-2,5-dienone rearranges to 2,3,6-tribromo-4-methylphenol.Under appropriate conditions debromination of bromodienones is competitive with rearrangement.Tetramethylammonium bromide in trifluoromethanesulfonic acid is an effective reagent for isomerization and disproportionation of bromophenols.Tetramethylammonium iodide in trifluoromethanesulfonic acid is an effective reagent for selective debromination of bromophenols at the ortho and para position.
- Fischer, Alfred,Henderson, George Narayanan
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p. 1045 - 1052
(2007/10/02)
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- MECHANISM OF ISOMERISATION OF ortho OR para BROMO PHENOLS IN SUPERACIDS
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In superacids ortho or para bromo phenols are isomerised into the meta bromo isomers.In SbF5-HF, the process is intramolecular and proceeds by a 1,2-Br shift.In CF3SO3H, the mechanism involves loss of bromine, followed by meta bromination.
- Jacquesy, Jean-Claude,Jouannetaud,Marie-Paule
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p. 1673 - 1676
(2007/10/02)
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- Electrophilic Substitution with Rearrangement. Part 9. Dienones derived from Brominations of o-, m-, and p-Cresol
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Regiospecific protodebromination of ring-substituted bromophenols derived from 2-, 3-, or 4-methylphenol can be effected by heating them with aqueous hydrogen iodide; the synthetic scope of this reaction has been explored.These di- and poly-bromophenols can generally be converted by further bromination in aqueous acetic acid into dienones , which have now been shown to have the 4-bromo-2,5-dienone rather than the 2-bromo-3,5-dienone structure.The rearrangemens of these dienones to ring-substituted polybromophenols by treatment with sulfuric acid have been investigated; where more than one product is formed, the regioselectivity differs from that prevailing in the corresponding direct bromination of the phenol with liquid bromine.The alternative rearrangements of these dienones in aprotic solvents with and without illumination have been compared with results obtained by reaction of methylphenols with bromine under the same conditions.Characteristic differences between the behaviours of 2-, 3-, and 4-methyl-substituted compounds reflect the specific reactions available to the particular dienones.
- Brittain, Judith M.,Mare, Peter B. D. de la,Newman, Paul A.
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- SUBSTITUTION META- TO AN AROMATIC HYDROXYL GROUP
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It is suggested that the bromination of 4-methylphenol in superacid solvents involves a 1,2-shift of bromine within a protonated bromodienone.
- Brittain, Judith M.,Mare, Peter B. D. de la,Newman, Paul A.
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p. 4111 - 4112
(2007/10/02)
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- meta-Bromination of Phenols in Superacids
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In SbF5-HF, para-alkylated or 2,6-dialkylated phenols (and their ethers) react with bromine to give the corresponding meta-bromo-substituted compounds; the mechanism implies bromination of the O-protonated substrate.
- Jacquesy, Jean-Claude,Jouannetaud, Marie-Paule,Makani, Siki
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p. 110 - 111
(2007/10/02)
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