- Decarboxylative cross-nucleophile coupling via ligand-to-metal charge transfer photoexcitation of Cu(ii) carboxylates
-
Reactions that enable carbon–nitrogen, carbon–oxygen and carbon–carbon bond formation lie at the heart of synthetic chemistry. However, substrate prefunctionalization is often needed to effect such transformations without forcing reaction conditions. The development of direct coupling methods for abundant feedstock chemicals is therefore highly desirable for the rapid construction of complex molecular scaffolds. Here we report a copper-mediated, net-oxidative decarboxylative coupling of carboxylic acids with diverse nucleophiles under visible-light irradiation. Preliminary mechanistic studies suggest that the relevant chromophore in this reaction is a Cu(ii) carboxylate species assembled in situ. We propose that visible-light excitation to a ligand-to-metal charge transfer (LMCT) state results in a radical decarboxylation process that initiates the oxidative cross-coupling. The reaction is applicable to a wide variety of coupling partners, including complex drug molecules, suggesting that this strategy for cross-nucleophile coupling would facilitate rapid compound library synthesis for the discovery of new pharmaceutical agents. [Figure not available: see fulltext.].
- Li, Qi Yukki,Gockel, Samuel N.,Lutovsky, Grace A.,DeGlopper, Kimberly S.,Baldwin, Neil J.,Bundesmann, Mark W.,Tucker, Joseph W.,Bagley, Scott W.,Yoon, Tehshik P.
-
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- Site-Selective Alkoxylation of Benzylic C?H Bonds by Photoredox Catalysis
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Methods that enable the direct C?H alkoxylation of complex organic molecules are significantly underdeveloped, particularly in comparison to analogous strategies for C?N and C?C bond formation. In particular, almost all methods for the incorporation of alcohols by C?H oxidation require the use of the alcohol component as a solvent or co-solvent. This condition limits the practical scope of these reactions to simple, inexpensive alcohols. Reported here is a photocatalytic protocol for the functionalization of benzylic C?H bonds with a wide range of oxygen nucleophiles. This strategy merges the photoredox activation of arenes with copper(II)-mediated oxidation of the resulting benzylic radicals, which enables the introduction of benzylic C?O bonds with high site selectivity, chemoselectivity, and functional-group tolerance using only two equivalents of the alcohol coupling partner. This method enables the late-stage introduction of complex alkoxy groups into bioactive molecules, providing a practical new tool with potential applications in synthesis and medicinal chemistry.
- Lee, Byung Joo,DeGlopper, Kimberly S.,Yoon, Tehshik P.
-
supporting information
p. 197 - 202
(2019/11/26)
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- Palladium-Catalyzed Alkoxycarbonylation of sec-Benzylic Ethers
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Herein, we report the palladium-catalyzed synthesis of 3-arylpropionate esters starting from secondary benzylic ethers. With this investigation it could be shown that ethers are suitable starting materials in addition to the established carbonylation reactions of olefins, alcohols, or aryl halides.
- Beller, Matthias,Jackstell, Ralf,Maes, Bert U. W.,Schneider, Carolin
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supporting information
(2020/02/25)
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- Iodine-catalyzed transformation of aryl-substituted alcohols under solvent-free and highly concentrated reaction conditions
-
Iodine-catalyzed transformations of alcohols under solvent-free reaction conditions (SFRC) and under highly concentrated reaction conditions (HCRC) in the presence of various solvents were studied in order to gain insight into the behavior of the reaction intermediates under these conditions. Dimerization, dehydration and substitution were the three types of transformations observed with benzylic alcohols. Dimerization and substitution reactions were predominant in the case of primary- and secondary alcohols, whereas dehydration prevailed in the case of tertiary alcohols. The relative reactivity of substituted 1-phenylethanols in I2-catalyzed dimerization under SFRC provided a good Hammett plot ρ+ = -2.8 (r2 = 0.98), suggesting the presence of electron-deficient intermediates with a certain degree of developed charge in the rate-determining step.
- Jereb, Marjan,Vra?i?, Dejan
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p. 747 - 762
(2018/01/17)
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- Redox-Switchable Hydroelementation of a Cobalt Complex Supported by a Ferrocene-Based Ligand
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The first crystallographically characterized tetrahedral cobalt salen (salen = N,N′-ethylenesalicylimine) complex was synthesized by using a 1,1′-ferrocene derivative, salfen (salfen = 1,1′- di(2,4-di-tert-butyl-6-salicylimine)ferrocene). The complex undergoes two oxidation events at low potentials, which were assigned as ligand centered by comparison to the corresponding zinc complex. The cobalt complex was found to catalyze the hydroalkoxylation of styrenes, similarly to related square planar cobalt salen complexes, likely due to its fluxional behavior in alcoholic solvents. Furthermore, the one-electron-oxidized species was found to be inactive toward hydroalkoxylation. Thus, the hydroalkoxylation reactivity could be turned on/off in situ by redox chemistry.
- Shepard, Scott M.,Diaconescu, Paula L.
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p. 2446 - 2453
(2016/08/16)
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- Direct synthesis of ethers from aldehydes and ketones. One-pot reductive etherification of benzaldehydes, alkyl aryl ketones, and benzophenones
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Benzyl alcohols formed by the reduction of benzaldehydes, alkyl aryl ketones, and benzophenones with sodium tetrahydridoborate in alcohols undergo in situ etherification with the solvent in the presence of a catalytic amount of HCl. Thus the process may be regarded as one-pot transformation of carbonyl compounds into the corresponding benzyl ethers. The yields of ethers depend on the substituent nature in the aromatic fragment of the initial carbonyl compound and on the alcohol used as reduction medium.
- Mochalov,Fedotov,Trofimova,Zefirov
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p. 503 - 512
(2016/06/13)
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- Hydrochloric acid as an efficient catalyst for intermolecular condensation of alcohols. A simple and highly efficient synthesis of unsymmetrical ethers from benzylic alcohols and alkanols
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Benzylic alcohols and diarylmethanols with electron-donating substituents in the aromatic ring reacted with aliphatic alcohols in the presence of a catalytic amount of HCl to give the corresponding alkyl arylmethyl ethers. The reactivity of diarylmethanols in the intermolecular dehydration depended on the nature of substituents in the aromatic rings and structure of aliphatic alcohol.
- Mochalov,Fedotov,Trofimova,Zefirov
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p. 1217 - 1231
(2015/11/09)
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- Hydroalkoxylation of unactivated olefins with carbon radicals and carbocation species as key intermediates
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A unique Markovnikov hydroalkoxylation of unactivated olefins with a cobalt complex, silane, and N-fluoropyridinium salt is reported. Further optimization of reaction conditions yielded high functional group tolerance and versatility of alcoholic solvent employed, including methanol, i-propanol, and t-butanol. Use of trifluorotoluene as a solvent made the use of alcohol in stoichiometric amount possible. Mechanistic insight into this novel catalytic system is also discussed. Experimental results suggest that catalysis involves both carbon radical and carbocation intermediates.
- Shigehisa, Hiroki,Aoki, Tatsuya,Yamaguchi, Sumiko,Shimizu, Nao,Hiroya, Kou
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supporting information
p. 10306 - 10309
(2013/08/23)
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- Selective synthesis of unsymmetrical ethers from different alcohols catalyzed by sodium bisulfite
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An efficient method for the preparation of unsymmetrical ethers from alcohols catalyzed by sodium bisulfite is reported. The procedure enables the direct dehydration of primary, secondary, and tertiary benzylic alcohols with aliphatic alcohols in the abse
- Yu, Jun-Lai,Wang, Hui,Zou, Kai-Feng,Zhang, Jia-Rui,Gao, Xiang,Zhang, Dan-Wei,Li, Zhan-Ting
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p. 310 - 315
(2013/01/15)
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- Effects of phosphorus substituents on reactions of α- alkoxyphosphonium salts with nucleophiles
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The effects of phosphorus substituents on the reactivity of α-alkoxyphosphonium salts with nucleophiles has been explored. Reactions of α-alkoxyphosphonium salts, prepared from various acetals and tris(o-tolyl)phosphine, with a variety of nucleophiles proceeded efficiently. These processes represent the first examples of high-yielding nucleophilic substitution reactions of α-alkoxyphosphonium salts. The reactivity of these salts was determined by a balance between steric and electronic factors, respectively, represented by cone angles θ and CO stretching frequencies ν (steric and electronic parameters, respectively). In addition, a novel reaction of α-alkoxyphosphonium salts derived from Ph3P with Grignard reagents was observed to take place in the presence of O2 to afford alcohols in good yields. A radical mechanism is proposed for this process that has gained support from isotope-labeling and radical-inhibition experiments. A dramatic change in the reactivity of an α-alkoxyphosphonium salt toward nucleophiles is observed due to the steric and electronic nature of the phosphine substituents. By changing the type of phosphorus substituents, the reaction pathway can be controlled to proceed selectively by substitution or a new radical reaction (see scheme; OTf=trifluoromethansulfonate, TMS=trimethylsilyl, o-tol=tolyl). Copyright
- Goto, Akihiro,Otake, Kazuki,Kubo, Ozora,Sawama, Yoshinari,Maegawa, Tomohiro,Fujioka, Hiromichi
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p. 11423 - 11432
(2012/11/07)
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- Catalytic hydroalkoxylation of alkenes by iron(III) catalyst
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Catalytic hydroalkoxylation of alkenes by iron(III) chloride in the presence of toluenesulfonic acid (TsOH) was developed in moderate to good yields up to 91%. Intramolecular cyclization of 5-hydroxyl pentene afforded 2-methyltetrahedronfuran in 63% yield.
- Ke, Fang,Li, Zhengkai,Xiang, Haifeng,Zhou, Xiangge
-
supporting information; experimental part
p. 318 - 320
(2011/02/26)
-
- Silica-supported KHSO4: An efficient system for activation of aromatic terminal olefins
-
Potassium hydrogen sulfate adsorbed on chromatography-grade silica gel activates electron-rich aromatic terminal olefins towards nucleophilic attack at the benzylic position by alcohols. Temperature plays a crucial role and facilitates suppressing nucleophilic reaction in favor of dimerization of the terminal olefin. Georg Thieme Verlag Stuttgart - New York.
- Das, Ram Nath,Sarma, Kuladip,Pathak, Madan Gopal,Goswami, Amrit
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supporting information; experimental part
p. 2908 - 2912
(2011/02/25)
-
- Bifunctional copper catalysts for an atom efficient ether synthesis
-
A direct etherification of aromatic ketones and aliphatic alcohols into the corresponding asymmetrical ethers by the use of a bifunctional heterogeneous copper catalyst is described. The reaction protocol reveals to be versatile and convenient respect to the traditional ether synthesis for both environmental and practical concerns.
- Zaccheria, Federica,Psaro, Rinaldo,Ravasio, Nicoletta
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experimental part
p. 5221 - 5224
(2009/12/06)
-
- Chemoselective etherification of benzyl alcohols using 2,4,6-trichloro-1,3, 5-triazine and methanol or ethanol catalyzed by dimethyl sulfoxide
-
An efficient method for the transformation of benzyl alcohols into their methyl or ethyl ethers has been established using 2,4,6-trichloro-1,3,5-triazine (TCT) and dimethyl sulfoxide in methanol or ethanol. This procedure chemoselectively converts benzylic hydroxys into their methyl or ethyl ethers in the presence of aliphatic or phenolic hydroxys. Georg Thieme Verlag Stuttgart.
- Sun, Lili,Guo, Yuping,Peng, Guisheng,Li, Chunbao
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experimental part
p. 3487 - 3491
(2009/05/26)
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- SELECTIVE SPLITTING OF SUBSTITUTED BISBENZYLAMIDES AND BISBENZYLAMINES
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The invention relates to a method for the area-selective splitting of secondary amines or amides.
- -
-
Page/Page column 14
(2008/06/13)
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- NBS-catalyzed hydroamination and hydroalkoxylation of activated styrenes
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(Chemical Equation Presented) N-Bromosuccinimide efficiently catalyzes the hydroamination and hydroalkoxylation of activated styrenes using tosylamides, carbamates, and alcohols as the nucleophiles to afford amino and ether derivatives, respectively. Both
- Talluri, Siva Kumar,Sudalai, Arumugam
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p. 855 - 857
(2007/10/03)
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- Tri-n-butylstannyl chloride-sodium cyanoborohydride mediated regioselective reductive demethoxylation of alkyl methyl ketals
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A regioselective reductive demethoxylation of alkyl methyl ketals employing sodium cyanoborohydride in the presence of a catalytic amount of tri-n-butyltin chloride as Lewis acid is described.
- Srikrishna,Viswajanani
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p. 621 - 625
(2007/10/03)
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- Reaction of Hydrazones with Methoxy(tosyloxy)iodobenzene (MTIB): Tosylate Formation under Oxidative Conditions
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Treatment of aromatic hydrazones 1 containing electron-withdrawing, reduction sensitive substituents with MTIB gives the corresponding tosylates 2 in high yield. When the tosylate is particularly reactive the thermodynamically more stable methyl ether 3 is isolated. Analogous reactions with DAIB give acetates 4 in high yield. Dialkyl hydrazones give olefinic products (e.g. 7 and 8). (+)-Camphor hydrazone 1k with either MTIB or DAIB gives both camphene 12 (major product) and tricyclene 11 (minor product) suggesting that a carbene pathway accounts for some of the material formed in these oxidations.
- Ramsden, Christopher A.,Rose, Helen L.
-
-
- A mild and simple procedure for the reductive cleavage of acetals and ketals
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A convenient, mild and simple procedure, employing sodium cyanoborohydride in the presence of either catalytic or stoichiometric amount of boron trifluoride etherate in dry THF, for the reductive cleavage of the acetals and ketals is described.
- Srikrishna, Adusumilli,Viswajanani, Ranganathan
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p. 3339 - 3344
(2007/10/02)
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- ANOMALOUS REDUCTION OF ALIPHATIC-AROMATIC KETONES BY THE COMPLEX HYDRIDES OF BORON
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During the reduction of XC6H4COCH3 by the action of sodium borohydride or potassium borohydride in a water-methanol medium the ethers XC6H4CH(OCH3)CH3 and not the corresponding alcohols were obtained.The formation of the ethers indicates that the O-Calkyl (and not O-B) bond is broken in the intermediate tetraalkoxyborate if a stable carbocation of the benzylic type, further stabilized by an electron-donor group at the ortho or para position of the benzene ring, is formed.
- Dem'yanovich, V.M.,Khlebnikov, V.A.
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p. 255 - 259
(2007/10/02)
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- Nucleophilic Substitiution Reactions of 1-Phenylethyl Benzenesulfonates with Anilines in Methanol-Acetonitrile
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Nucleophilic substitution reactions of 1-phenylethyl benzenesulfonates with anilines have been investigated in methanol-acetonitrile mixtures at 25 deg C.Magnitudes of the Hammett coefficients ρX, ρY, and ρZ indicate that
- Lee, Ikchoon,Kim, Hyung Yoon,Kang, Han Keun,Lee, Hai Whang
-
p. 2678 - 2683
(2007/10/02)
-
- Rhodium-catalyzed oxidation of organic compounds with t-butyl hydroperoxide
-
The metal-catalyzed oxidation of organic compounds with t-butyl hydroperoxide (TBHP) and RhCl(PPh3)3 and Rh+(diphos) has been investigated.Under appropriate conditions both catalysts give identical results: anthracene is converted into anthraquinone, 1-octene into 2-octanone, and 1-phenylethanol into acetophenone, with 95 to 100percent isolated yields.The phosphine ligands of the catalysts are rapidly attacked during the oxidations, but this does not decrease the activity of the catalytic system.The formation of 2-octanone from 1-octene is believed to be due to a metal-centered mechanism rather than to a free radical pathway.The same mechanism should apply to the oxidation of anthracene and 1-phenylethanol.
- Mueller, Paul,Idmoumaz, Hamid
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p. 187 - 200
(2007/10/02)
-
- Improved preparation of precocene II. Unexpected results in the reduction of alkoxy substituted acetophenones and 4-chromanones with sodium borohydride
-
An improved preparation of natural pro-allatocidin precocene II (6) is reported. Starting from methoxyhydroquinone (1), Fries condensation with acid 2 led to the hydroxychromanone 3, which by further methylation, reduction and dehydration afforded chromene 6 in 77% overall yield. In addition, complementary studies related to the synthetic sequence have also been carried out, i.e., the influence of water contents on the initial Fries rearrangement and the scope of an anomalous reaction course in the reduction of aromatic ketones with NaBH4 MeOH in which, depending upon the activation of the carbonyl group, the formation of the methyl ether instead of that of the corresponding alcohol might be observed.
- Teixidor, Pilar,Camps, Francisco,Messeguer, Angel
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p. 2459 - 2465
(2007/10/02)
-
- ENHANCED NUCLEOPHILE SELECTIVITY IN THE PHOTOADDITION TO STYRENE. COMPARISON WITH THE THERMAL ADDITION
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The reactivity-selectivity properties of the sec-phenethyl carbenium ion and its analogues have been examined in binary-aqueous solutions of alcohols (ROH; R = Me, Et, CF3CH2, n-Bu, t-Bu, n-Pr, i-Pr), acetic acid, and in solutions containig external nucleophiles such as thiophenol, ethanethiol, acetate, and benzenesulfinate.Selectivity (S = k(Nuc)/k(H2O) is observed to be a function of the nucleophile, the ring substituent, thermal or photochemical conditions, irradiation time, and medium acidity.In the case of styrene, the photochemically generated (usually 254 nm, 1 h) species exhibits greater selectivity (up to two orders of magnitude) than its thermal counterpart, generated (usually 80 deg C, 2-4 d) in identical media, particularly in aqueous-rich solvent compositions.A rationale for these differences, supported by fluorescence quenching experiments, and the other effects upon selectivity will be discussed.
- Anderson, Steven W.,Yates, Keith
-
p. 2412 - 2421
(2007/10/02)
-
- Equilibrium Constants for the Interconversion of Substituted 1-Phenylethyl Alcohols and Ethers. A Measurement of Intramolecular Electrostatic Interactions
-
Equilibrium constants for the reactions of ring-substituted 1-phenylethyl alcohols with a series of aliphatic alcohols of pKa 12.4-16 to form the corresponding ethers, and for interconversion of the ethers, have been determined in 50:45:5 HOH/CF3CH2OH/ROH (v/v/v), μ = 0.5 (NaCIO4), at 25 deg C.Formation of ethers from the alcohols is favorable, with values of K = 3-74; replacement of water by methanol is favored by factors of 50-74.Equilibrium constants increase with increasing pKa of the alcohol with values of βeq = δlog K/δpKROH in the range 0.17-0.27.This is attributed to hydrogen bonding of the alcohol to the solvent and to an electrostatic interaction between substituents on the alcohol and the aryl group.The contribution from hydrogen bonding to the solvent is estimated to be β = 0.17; for 90percent HOH it is 0.25.An increase in βeq with electron-withdrawing substituents on the benzene ring and a complementary increase in ρeq with electron-donating substituents on ROH are described by an electrostatic interaction coefficient τ = δβeq/δ? = δρeq/δpKROH = 0.10 +/- 0.01.No change in τ for dipole-dipole interactions was observed with increasing water concentration in the range 50-90percent (v/v).The electrostatic interactions that are described by τ can cause changes in structure-reactivity parameters, such as ρ or β, in the absence of changes in transition-state structure.
- Rothenberg, Marc E.,Richard, John P.,Jencks, William P.
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p. 1340 - 1346
(2007/10/02)
-
- Photochemical Electron-transfer Reaction between Aromatic Olefins and Metal Ions. Dependence of the Reaction Course on the Structure of the Olefins
-
To investigate the photochemical electron transfer from aromatic olefins to copper(II) or iron(III) ions, a series of substituted styrenes (1) was irradiated in the presence of copper(II) or iron(II) salts in methanol, which gave dimethoxylated monomers (2) and one or more of three types of dimethoxylated dimers .The formation of these products are reasonably attributed to the participation of hte cation radicals of the olefins generated by electron transfer from excited olefins to the methal ions.Substituents on the substrates are found to govern the reaction products.
- Kojima, Masanobu,Sakuragi, Hirochika,Tokumaru, Katsumi
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p. 521 - 524
(2007/10/02)
-
- GENERAL BASE CATALYSIS OF THE ADDITION OF HYDROXYLIC REAGENTS TO UNSTABLE CARBOCATIONS AND ITS DISAPPEARANCE.
-
General base catalysis of the addition of ROH is significant for 1-phenylethyl carbocations of moderate stability and is most important for weakly basic alcohols. The Bronsted slope for catalysis of the addition of trifluoroethanol to the 1-(4-methoxyphenyl)ethyl carbocation is beta equals 0. 08. The development of positive charge on the attacking alcohol decreases with decreasing stability of the carbocation. It is concluded that the observed catalysis involves hydrogen bonding and represents the transition region between fully concerted, coupled general acid-base catalysis and specific acid catalysis with solvation of the proton in the transition state.
- Richard,Jencks
-
p. 1396 - 1401
(2007/10/02)
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- Formation and Stability of Ring-Substituted 1-Phenylethyl Carbocations
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The solvolysis of 1-phenylethyl derivatives with electron-donating 4-substituents in 50:50 trifluoroethanol:water(v:v) occurs at a rate that is independent of azide concentration but gives yields of the corresponding azide adducts of up to 98percent by trapping a carbocation intermediate.Rate constants for reactions of the cations with solvent range from 2 x 103 s-1 (4-Me2N) to 4 x 109 s-1 (4-Me), assuming a diffusion-controlled rate constant of 5 x 109 M-1 s-1 for their reactions with azide and thiol anions.Correlation of the rate constants following the Yukawa-Tsuno treatment gives ρn = 2.5, ρr = 5.2, and r+ = 2.1 for the reaction with trifluoroethanol, and ρn = 2.7, ρr = 4.9, and r+ = 1.8 for the reaction with water.The reverse reaction, acid-catalyzed cleavage of substituted 1-phenylethyl alcohols to give the corresponding carbocation, follows ρn = -4.9, ρr = -4.4, and r+ = 0.9.This gives values of ρn = -7.6, ρr = -9.3, and r+ = 1.2 for formation of the cations at equilibrium.There is an imbalance in the development of resonance delocalization, analogous to the "nitroalkane anomaly", that is consistent with a dependence of the fraction of maximal resonance delocalization on the fraction of rehybridization or C-X bond cleavage.Solvent effects on carbocation stability in aqueous-organic mixtures are relatively small.They depend mainly on the nucleophilicity of the solvent components and a specific solvent effect of trifluoroethanol on the reactivity of hydroxylic nucleophiles, including trifluoroethanol itself.The "ionizing power" of the solvent has only a small effect on cation stability, and there is little effect of the concentration or nature of added salts.
- Richard, John P.,Rothenberg, Marc E.,Jencks, William P.
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p. 1361 - 1372
(2007/10/02)
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- Reactions of Substituted 1-Phenylethyl Carbocations with Alcohols and Other Nucleophilic Reagents
-
Selectivities of a series of substituted 1-phenylethyl carbocations toward alcohols and other nucleophiles have been determined by product analysis.The 1-(4-dimethylamino)phenyl)ethyl carbocation exhibits a high selectivity in its reactions with alcohols , with KEtOH/KTFE = 140 and βnuc = 0.5.The selectivity for activation-limited reactions with alcohols decreases progressively with increasing reactivity of the carbocation, in contrast to the behavior expected from the N+ scale of reactivity.A sharper drop in selectivity for carbocations that react faster than ca. 109 S-1 is attributed to an approach to limiting rate constants for the more reactive alcohol.The limiting selectivity of kEtOH/kTFE = 2 for carbocations with ks ca. 1011 S-1 may represent reaction from a pool of solvent molecules in which there is a modest charge-dipole interaction between the alcohol and carbocation.The relatively low reactivity of water corresponds to that expected for an alcohol of pKa ca. 13.This is ascribed to an imbalance between charge development and solvation of the transition state compared with H3O+.Substituted acetate anions react with the 1-(4-methoxyphenyl)ethyl carbocation with βnuc = 0.13.The selectivity decreases with increasing cation reactivity as the carboxylate ions approach limiting rate constants of ca. 5 * 108 M-1 s-1.This relatively low limit is attributed to a requirement for desolvation of basic oxygen anions before reaction.A dependence of solvent selectivity on the leaving group shows that the 1-(4-methylphenyl)ethyl carbocation reacts with solvent, in part, through an ion pair.Azide ion reacts from a pool that can be described by an equilibrium constant of Kas = 0.3 M-1.Styrene formation from this carbocation is catalyzed by a leaving carboxylate ion and by added buffers, wih β = 0.14.The equilibrium constant for the formation of a reactive base-cation pair is ca. 0.04 M-1.Rate constants for collapse of the ion pair, to form ester, and for proton removal, to form 4-methylstyrene, were estimated to be approximately 1.6 * 1010 s-1 and 6 * 107 s-1, respectively.The rate constants for deprotonation and for hydration of the styrene give the acid dissociation constant of the carbocation to form 4-methylstyrene, pKA = -11.2.
- Richard, John P.,Jencks, William P.
-
p. 1373 - 1383
(2007/10/02)
-
- Silicon-Mediated Synthesis of Bibenzyl Systems: Synthesis of Ring and Side-Chain Functionalized Hexestrol Derivatives
-
Derivatives of hexestrol , a non-steroidal estrogen, bearing photochemically reactive functional groups or γ-emmitting radionuclides, are useful as affinity labeling agents for the estrogen receptor or as imaging agents for receptor positive breast tumors, respectively.We have developed convenient synthetic routes to two side chain functionalized and aromatic ring functionalized hexestrol derivatives, based on a direct benzylic coupling reaction mediated by allylsilanes or silyl ketene acetals. 1-Dehydrohexestrol and variousaromatic ring substituted 1-dehydrohexestrol derivatives can be prepared by coupling 3-(trimethylsilyl)-1-(4-methoxyphenyl)propene with various reactive benzylic derivatives, and pentestrol derivatives are prepared by the coupling of the silyl ketene acetal derivative of p-methoxyphenyl acetic ester with benzylic derivatives.The R*,S* (erythro) and R*,R* (threo) diastereomers formed in each case can be separated readily by chromatography and recrystallization.This silicon-mediated approach to functionalized hexestrol derivatives provides a convenient route to many compounds of interest as biochemical probes and receptor-based diagnostic reagents.
- Mohan, Raju,Katzenellenbogen, John A.
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p. 1238 - 1246
(2007/10/02)
-
- Retentive Solvolysis. Part 12. Mechanism of the Reaction of Optically Active 1-(p-Methoxyphenyl)ethyl Trifluoroacetate with Phenol and Metanol in Benzene and Cyclohexane
-
The rate, product distribution, and stereochemical course for the reactions of 0.05-0.1M-1-(p-methoxyphenyl)ethyl trifluoroacetate (1) with methanol and phenol have been investigated in benzene or cyclohexane as solvent at 25.0 deg C.Below 1E-3M-methanol or -phenol the total kinetic order is two overall .The rates are virtually independent of the pyridine used to bind the trifluoroacetic acid produced.The major product from the phenol reaction, 1-(p-methoxyphenyl)ethyl phenyl ether, shows net retention (6-9percent) of configuration along with predominant racemization.In addition, the methyl ether product from the methanol reaction also undergoes net retention (24percent with 0.2M-methanol).The formation of the ethers with net retention of configuration can be accounted for by an intermolecular SNi mechanism.
- Okamoto, Kunio,Takeuchi, Ken'ichi,Inoue,Takeshi
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p. 842 - 848
(2007/10/02)
-
- Stereochemistry of Photosolvolysis of (-)-1-Phenylethyltrimethylammonium Iodide in Water and in Methanol, and Nucleophile Capture Ratios during Photosolvolysis of Some Benzylammonium Salts
-
The photosolvolysis of (-)-1-phenylethyltrimethylammonium iodide in water or methanol is characterised by extensive racemisation accompanied by some net configurational inversion, a result similar to that generally observed in thermal solvolysis via ion-pairs at chiral secondary centres.Recovered quaternary salt from the photolysis in water is only slightly if at all racemised, while likewise there is no observable epimerisation at nitrogen in recovered benzylammonium salts following photolysis in methanol of suitable derivatives of camphidine, trans-decahydroquinoline, and 4-phenylpiperidine.A strong preference for formation of the methyl ether rather than the alcohol is exhibited on either photochemical or thermal solvolysis of 1-p-methoxyphenylethyltrimethylammonium iodide in aqueous methanol, but nucleophile capture ratios during photosolvolysis of simple benzyltrimethylammonium salts in this mixed solvent system are much lower.
- Lillis, Veronica,Kenna, James Mc,Kenna, Jean Mc,Smith, Martin J.,Taylor, Paul S.,Williams, Ian H.
-
-