- Halogen-Lithium Exchange of Sensitive (Hetero)aromatic Halides under Barbier Conditions in a Continuous Flow Set-Up
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A halogen-lithium exchange reaction of (hetero)aromatic halides performed in the presence of various electrophiles such as aldehydes, ketones, Weinreb amides, and imines using BuLi as exchange reagent and a commercially available flow set-up is reported. The organolithiums generated in situ were instantaneously trapped with various electrophiles (Barbier conditions) resulting in the formation of polyfunctional (hetero)arenes. This method enables the functionalization of (hetero)arenes containing highly sensitive functional groups such as esters, which are not tolerated in batch conditions.
- Weidmann, Niels,Nishimura, Rodolfo H. V.,Harenberg, Johannes H.,Knochel, Paul
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supporting information
p. 557 - 568
(2020/09/18)
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- Light-driven MPV-type reduction of aryl ketones/aldehydes to alcohols with isopropanol under mild conditions
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Alcohols are versatile structural motifs of pharmaceuticals, agrochemicals and fine chemicals. With respect to green chemistry, the development of more sustainable and cost-efficient processes for converting ketones/aldehydes to alcohols is highly desired. Herein, a direct light-driven strategy for reducing ketones/aldehydes to alcohols using isopropanol as the reducing agent and solvent, in the presence of t-BuOLi, under an air atmosphere at room temperature is developed. This operationally simple light-promoted Meerwein-Ponndorf-Verley (MPV) type reduction can be used to produce various benzylic alcohol derivatives as well as applied to bioactive molecules and PEEK model compounds, demonstrating its application potential.
- Cao, Dawei,Xia, Shumei,Pan, Pan,Zeng, Huiying,Li, Chao-Jun,Peng, Yong
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supporting information
p. 7539 - 7543
(2021/10/12)
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- Nickel Catalyzed Intermolecular Carbonyl Addition of Aryl Halide
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In this study, we develop a nickel-catalyzed carbonyl arylation reaction employing aldehydes with aryl and allyl halides. Various aryl, α,β-unsaturated aldehyde and aliphatic aldehydes can be converted into their corresponding secondary alcohols in moderate-to-high yields. In addition, we extended this approach to develop an asymmetric reductive coupling reaction that combines nickel salts with chiral bisoxazoline ligands to give secondary alcohols with moderate enantioselectivity.
- Ishida, Seima,Suzuki, Hiroyuki,Uchida, Seiichiro,Yamaguchi, Eiji,Itoh, Akichika
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supporting information
p. 7483 - 7487
(2019/12/11)
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- Solvolytic reactivity of pyridinium ions
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The leaving group abilities of pyridine, 4-methylpyridine, and 4-chloropyridine in SN1 solvolytic reactions have been determined by analyzing the rate constants of X,Y-substituted benzhydrylpyridinium salts obtained in various solvents. By applying the linear free energy relationship equation, log k = sf (Ef + Nf), the nucleofuge specific parameters of 4-substituted pyridine have been extracted. Because of solvation in the reactant ground state, the reactivity (nucleofugality, Nf) of a given pyridine decreases as the polarity of the solvent increases. High slope parameters (sf > 1) may be due to the spread of the energy levels of the benzhydrylium ion/pyridine pair intermediates in comparison to benzhydrylium ion/chloride pairs (sf ≈ 1). Because of slow heterolysis step of pyridinium salts in various solvents, some are stable under normal conditions.
- Juric, Sandra,Kronja, Olga
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p. 314 - 319
(2015/05/05)
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- Nucleofugality of aliphatic carboxylates in mixtures of aprotic solvents and water
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The leaving group ability (nucleofugality) of fluoroacetate, chloroacetate, bromoacetate, dichloroacetate, trifluoroacetate, trichloroacetate, heptafluorobutyrate, formate, isobutyrate, and pivalate have been derived from the solvolysis rate constants of the corresponding X,Y-substituted benzhydryl carboxylates in 60 % and 80 % aqueous acetonitrile and 60 % aqueous acetone, applying the LFER equation: log k = sf(Ef + Nf). The experimental barriers (ΔG?,exp) for solvolyses of 11 reference dianisylmethyl carboxylates in these solvents correlate very well (r = 0.994 in all solvents) with ΔG?,model of the model σ-assisted heterolytic displacement reaction of cis-2,3-dihydroxycyclopropyl trans-carboxylates calculated earlier. Linear correlation observed between the log k for the reference dianisylmethyl carboxylates and the sf values enables estimation of the reaction constant (sfestim). Using the ΔG?,exp vs. ΔG?,model correlation, and taking the estimated sfestim, the nucleofugality parameters for other 34 aliphatic carboxylates have been determined in 60 % and 80 % aqueous acetonitrile and 60 % aqueous acetone. The most important variable that determines the reactivity of aliphatic carboxylates in aprotic solvent/water mixtures is the inductive effect of the group(s) attached onto the carboxylate moiety.
- Mati, Mirela,Denegri, Bernard,Kronja, Olga
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p. 375 - 384
(2015/10/12)
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- The reactivity of benzoates in mixtures of water and aprotic solvents
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Nucleofugalities of pentafluorobenzoate (PFB), 2,4,6-trifluorobenzoate (TFB), 2-nitrobenzoate, and 3,5-dinitrobenzoate (DNB) leaving groups have been derived from the solvolysis rate constants of the corresponding X,Y-substituted Z-benzhydryl benzoates in
- Matic, Mirela,Denegri, Bernard,Kronja, Olga
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p. 585 - 594
(2013/06/26)
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- Nucleofugality and nucleophilicity of fluoride in protic solvents
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A series of p-substituted benzhydryl fluorides (diarylfluoromethanes) were prepared and subjected to solvolysis reactions, which were followed conductometrically. The observed first-order rate constants k1(25 °C) were found to follow the correlation equation log k1(25 °C) = sf(Nf + Ef), which allowed us to determine the nucleofuge-specific parameters Nf and sf for fluoride in different aqueous and alcoholic solvents. The rates of the reverse reactions were measured by generating benzhydrylium ions (diarylcarbenium ions) laser flash photolytically in various alcoholic and aqueous solvents in the presence of fluoride ions and monitoring the rate of consumption of the benzhydrylium ions by UV-vis spectroscopy. The resulting second-order rate constants k-1(20 °C) were substituted into the correlation equation log k-1 = sN(N + E) to derive the nucleophilicity parameters N and sN for fluoride in various protic solvents. Complete Gibbs energy profiles for the solvolysis reactions of benzhydryl fluorides are constructed.
- Nolte, Christoph,Ammer, Johannes,Mayr, Herbert
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supporting information; scheme or table
p. 3325 - 3335
(2012/06/17)
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- CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldehydes, α,β-unsaturated ketones, and N-tosyl aldimines
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CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldehydes and α,β-unsaturated ketones at elevated temperatures were described. By using the microwave energy, CuCl/bipyridine-catalyzed addition reactions of arylboroxines with aldimines were also realized.
- Liao, Yuan-Xi,Hu, Qiao-Sheng
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experimental part
p. 7602 - 7607
(2011/11/12)
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- A nontransmetalation reaction pathway for anionic four-electron donor-based palladacycle-catalyzed addition reactions of arylborons with aldehydes
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A nontransmetalation reaction pathway for anionic four-electron donor-based (Type I) palladacycle-catalyzed addition reactions of arylborons with aldehydes is described. This new reaction pathway offers new catalysis opportunities for Type I palladacycle-catalyzed addition reactions such as the exceptionally low catalyst loading catalysis, with the catalyst loading as low as 0.0005 mol %. This new pathway may be applicable for other transition metal-catalyzed addition reactions and might lead to the development of new reactions including sequential/tandem reactions.
- Liao, Yuan-Xi,Xing, Chun-Hui,Israel, Matthew,Hu, Qiao-Sheng
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supporting information; experimental part
p. 3324 - 3328
(2011/06/28)
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- Selectivity of stabilized benzhydrylium ions
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Methyl carbonates (1-4-OCO2Me) and phenyl carbonates (2-4-OCO2Ph) were subjected to solvolysis in the series of aqueous ethanol, the product ratios were determined and the selectivities (k E/kw) of the correspon
- Denegri, Bernard,Matic, Mirela,Kronja, Olga
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scheme or table
p. 1440 - 1444
(2010/05/18)
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- Rh(I)/diene-catalyzed addition reactions of aryl/alkenylboronic acids with aldehydes
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[Rh(COD)Cl]2-catalyzed addition reactions of arylboronic acids with aldehydes, with low Rh(I) catalyst loading, are described. We also found that the reaction of arylboronic acids with α,β-unsaturated aldehydes greatly depends on the solvent and the steric hindrance of the reagents/substrates.
- Xing, Chun-Hui,Liu, Tao-Ping,Zheng, Jin Rong,Ng, Jaclynn,Esposito, Michelle,Hu, Qiao-Sheng
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experimental part
p. 4953 - 4957
(2009/12/03)
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- The rhodium-catalysed 1,2-addition of arylboronic acids to aldehydes and ketones with sulfonated S-Phos
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The rhodium-catalysed 1,2-addition of arylboronic acids to aryl aldehydes has been accomplished in high yield using sulfonated S-Phos, a water-soluble biaryl phosphine ligand which allows for catalyst recycling. The catalytic protocol has also been successful in the challenging arylation of ketones.
- White, James R.,Price, Gareth J.,Plucinski, Pawel K.,Frost, Christopher G.
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supporting information; experimental part
p. 7365 - 7368
(2010/03/03)
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- Nucleofugality of phenyl and methyl carbonates
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(Chemical Equation Presented) A series of X,Y-substituted benzhydryl phenyl carbonates 1 and X,Y-substituted benzhydryl methyl carbonates 2 were subjected to solvolysis in different methanol/water, ethanol/water, and acetone/water mixtures at 25°C. The LFER equation, log k = sf(Ef + Nf), was used to derive the nucleofuge-specific parameters (N f and sf) for phenyl carbonate (1LG) and methyl carbonate (2LG) leaving groups in a given solvent in SN1 type reaction. Kinetic measurements showed that phenyl carbonates solvolyze one order of magnitude faster than methyl carbonates. Optimized geometries of 1LG and 2LG at B3LYP/6-311G(d,p), B3LYP/6-311++G(d,p), and MP2(full)/6-311++G(d,p) levels revealed that negative charge delocalization in carbonate anions to all three oxygen atoms occurs due to negative hyperconjugation. Phenyl carbonate (1LG) is a better leaving group (Nf = -0.84 ± 0.07 in 80% v/v aq EtOH) than methyl carbonate 2LG (Nf = -1.84 ± 0.07 in 80% v/v aq EtOH) because of more pronounced negative hyperconjugation, which is characterized with a more elongated RO-C bond and more increased RO-C-CO angle in 1LG than in 2LG. Calculated affinities of benzhydryl cation toward methyl and phenyl carbonate anions (ΔΔEaff = 11.7 kcal/mol at the B3LYP/6-311++G(d,p) level and ΔΔEaff = 2.7 kcal/mol at the PCM-B3LYP/6-311++G(d,p) level in methanol, respectively) showed that 1LG is more stabilized than 2LG, which is in accordance with greater solvolytic reactivity of 1 than 2.
- Denegri, Bernard,Kronja, Olga
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p. 8427 - 8433
(2008/03/12)
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- Alkynes as activators in the nickel-catalysed addition of organoboronates to aldehydes
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Alkynes act not as substrates but as co-catalysts in the presence of a nickel catalyst, an organoboronate and an aldehyde to promote the addition reaction between the substrates in combination with H2O. The Royal Society of Chemistry 2005.
- Takahashi, Go,Shirakawa, Eiji,Tsuchimoto, Teruhisa,Kawakami, Yusuke
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p. 1459 - 1461
(2007/10/03)
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- Solvent Nucleophilicity
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The rates of the reactions of benzhydrylium ions (diarylcarbenium ions) with solvent mixtures of variable composition (water/acetonitrile, methanol/acetonitrile, ethanol/acetonitrile, ethanol/water, and trifluoroethanol/water) have been determined photometrically by conventional UV-vis spectroscopy, stopped-flow methods, and laser flash techniques. It has been shown that the first-order rate constants follow the previously published relationship log k(20°C) = s(N+E), where E is an empirical electrophilicity parameter, N is an empirical nucleophilicity parameter, and s is a nucleophile-specific slope parameter. From plots of log k versus E of the benzhydrylium ions are derived the solvent nucleophilicity parameters s and N, the latter of which are designated as N1 to emphasize that their use in the quoted correlation equation gives rise to first-order rate constants. A linear correlation between N1 and Kevill's solvent nucleophilicity NT based on S-methyldibenzothiophenium ions is reported, which allows one to interconvert the two sets of data. Because the N1 values are directly comparable to the previously reported nucleophilicity parameters N for π-systems (www.cup.uni-muenchen.de/oc/mayr/), the systematic design of Friedel-Crafts reactions with solvolytically generated carbocations becomes possible.
- Minegishi, Shinya,Kobayashi, Shinjiro,Mayr, Herbert
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p. 5174 - 5181
(2007/10/03)
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- SN1 reactions with inverse rate profiles
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Carbocations may accumulate during solvolysis reactions! The fact that fast ionization followed by slow trapping of the carbocation R+ is a characteristic pattern of many solvolysis reactions requires that the generally accepted energy profiles of these reactions be revised.
- Denegri, Bernard,Minegishi, Shinya,Kronja, Olga,Mayr, Herbert
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p. 2302 - 2305
(2007/10/03)
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- Direct observation of aldehyde insertion into rhodium-aryl and -alkoxide complexes
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Several organorhodium(I) complexes of the general formula (PPh3)2(CO)RhR (R = p-tolyl, o-tolyl, Me) were isolated and were shown to insert aryl aldehydes into the aryl-rhodium(I) bond. Under nonaqueous conditions, these reactions provided ketones in good yield. The stability of the arylrhodium(I) complexes allowed these reactions to be run also in mixtures of THF and water. In this solvent system, diarylmethanols were generated exclusively. Mechanistic studies support the formation of ketone and diarylmethanol by insertion of aldehyde into the rhodium-aryl bond and subsequent β-hydride elimination or hydrolysis to form diaryl ketone or diarylmethanol products. Kinetic isotope effects and the formation of diarylmethanols in THF/water mixtures are inconsistent with oxidative addition of the acyl carbon-hydrogen bond and reductive elimination to form ketone. Moreover, the intermediate rhodium diarylmethoxide formed from insertion of aldehyde was observed directly during the reaction. Its structure was confirmed by independent synthesis. This complex undergoes β-hydrogen elimination to form a ketone. This alkoxide also reacts with a second aldehyde to form esters by insertion and subsequent β-hydrogen elimination. Thus, reactions of arylrhodium complexes with an excess of aldehyde formed esters by a double insertion and β-hydrogen elimination sequence.
- Krug, Christopher,Hartwig, John F.
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p. 1674 - 1679
(2007/10/03)
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- Spectral properties and reactivity of diarylmethanol radical cations in aqueous solution. Evidence for intramolecular charge resonance
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Spectral properties and reactivities of ring-methoxylated diarylmethane and diarylmethanol radical cations, generated in aqueous solution by pulse and γ-radiolysis and by the one-electron chemical oxidant potassium 12-tungstocobalt(III)ate, have been studied. The radical cations display three bands in the UV, visible, and vis-NIR regions of the spectrum. The vis-NIR band is assigned to an intramolecular charge resonance interaction (CR) between the neutral donor and charged acceptor rings, as indicated by the observation that the relative intensity of the vis-NIR band compared to that of the UV and visible bands does not increase with increasing substrate concentration and that the position and intensity of this band is influenced by the ring-substitution pattern. In acidic solution (pH = 4), monomethoxylated diarylmethanol radical cations 1a.+-1e.+ decay by Ca-H deprotonation [k = (1.7-1.9) x 104 S-1] through the intermediacy of a ketyl radical, which is further oxidized in the reaction medium to give the corresponding benzophenones, as evidenced by both time-resolved spectroscopic and product studies. With the dimethoxylated radical cation 2.+, Ca-H deprotonation is instead significantly slower (k = 6.7 × 102 s-1). In basic solution, 1.+-1e.+ undergo -OH-induced deprotonation from the α-OH group with kOH ≈ 1.4 × 1010 M-1 s-1, leading to a ketyl radical anion, which is oxidized in the reaction medium to the corresponding benzophenone.
- Bietti, Massimo,Lanzalunga, Osvaldo
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p. 2632 - 2638
(2007/10/03)
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- The nature of the transition state in diarylmethyl cation - Nucleophile combination reactions as probed by secondary α-deuterium isotope effects
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Transition-state structures for the carbocation-nucleophile combination reactions of (4-substituted-4′-methoxydiphenyl)methyl cations with water, chloride, and bromide ions in acetonitrile-water mixtures have been investigated by measuring the secondary α-deuterium kinetic and equilibrium isotope effects. Rate constants in the combination direction were measured with laser flash photolysis. Equilibrium constants were measured for the water reaction by a comparison method in moderately concentrated sulfuric acid solutions, for the bromide reaction via the observation of reversible combination, and for the chloride reaction from the ratio of the combination rate constant and the rate constant for the ionization of the diarylmethyl chloride product. The fraction of bond making in the transition state has been calculated as the ratio log (kinetic isotope effect):log (equilibrium isotope effect). For the water reaction, there is 50-65% bond making in the transition state; this is also true for cations that are many orders of magnitude less reactive. The same conclusions, 50-65% bond formation in the transition state independent of reactivity, have previously been made in corre-lations of log kw vs. log KR. Thus, two quite different measures of transition structure provide the same result. The kH:kD values for the halide combinations in 100% acetonitrile are within experimental error of unity. This is consistent with suggestions that these reactions are occurring with diffusional encounter as the rate-limiting step. Addition of water has a dramatic retarding effect on the halide reactions, with rate constants decreasing steadily with increased water content. Small inverse kinetic isotope effects are observed (in 20% acetonitrile:80% water) indicating that carbon-halogen bond formation is rate-limiting. Comparison of the kinetic and equilibrium isotope effects shows ~25 and ~40% bond formation in the transition states for the reactions with bromide and chloride, respectively.
- Van Pham, Thuy,McClelland, Robert A.
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p. 1887 - 1897
(2007/10/03)
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- Ni(II)/Zn-mediated chemoselective arylation of aromatic aldehydes: Facile synthesis of diaryl carbinols
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(equation presented) Direct arylation of aromatic aldehydes with aryl bromides in the presence of Ni(II)Zn was investigated. The choice of ligand in this nickel-catalyzed coupling was critical to the formation of the secondary alcohols. Monodentate phosphine ligands were ineffective, whereas NiBr2-(dppe)/Zn successfully catalyzed this reductive coupling reaction. The reaction were mild and diarylcarbinols with a variety of functional groups such as ketone, ester, amide, and nitrile groups were readily prepared.
- Majumdar, Kanak Kanti,Cheng, Chien-Hong
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p. 2295 - 2297
(2007/10/03)
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- Rhodium-catalyzed addition of organoboronic acids to aldehydes
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Highly inert to ionic additions to aldehydes, aryl- and 1- alkenylboronic acids succumb to a catalytic variant mediated by a [Rh(acac)(CO)2]-diphosphane complex in aqueous phase at 80-95°C to yield secondary alcohols [Eq. (a)]. A key step in the catalytic cycle is the transmetalation between the boron reagent and the rhodium complex. L(n) = diphosphane (e.g. 1,1'-bis(diphenylphosphanyl)ferrocene); R = aryl, 1- alkenyl; R'= alkyl, aryl; acac = acetylacetonate.
- Sakai, Masaaki,Ueda, Masato,Miyaura, Norio
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p. 3279 - 3281
(2007/10/03)
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- Process for producing benzhydrols
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There is disclosed a process for producing benzhydrls by reacting an arylmetal compound with an aromatic aldehyde. According to this process, benzhydrols useful as raw materials for medicines and photopolymerization initiators can be produced in a high yield and industrially advantageously.
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- Photochemical Reaction of phosphonic Acids. Application to a Photo-degradable Surfactant
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Upon UV-irradiation, the C-P bonds of methylphosphonic acids were cleaved in water (pH 12) to give 4-alkoxyphenyl p-tolyl ketones and orthophosphate in high efficiency.It was demonstrated that the acids can be used as photo-degradable surfactants.
- Okamoto, Yoshiki,Yoshida, Hidetoshi,Takamuku, Setsuo
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p. 569 - 572
(2007/10/02)
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- Ionisation and Dissociation of Diarylmethyl Chlorides in BCl3/CH2Cl2 Solution: Spectroscopic Evidence for Carbenium Ion Pairs
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The ionisation equilibria of diarylmethyl chlorides Ar2CHCl (Ar = p-CH3O-C6H4, p-PhO-C6H4, p-CH3-C6H4) reacting with BCl3 in CH2Cl2 to give ion-pairs Ar2CH(+)BCl4(-) (KI), and the dissociation of these (KD) were studied by conductimetry and spectro-photometry.The molar conductivities are almost independent of the nature of the aryl group (ca. 3.5E-3 Sm2/mol at -70 deg C).The ionisation constants KI increase strongly with increasing electron releasing ability of the p-substituents.The standard ionisation enthalpies and entropies for (p-CH3-C6H4)2CHCl and (p-PhO-C6H4)(Ph)CHCl, calculated from the KI at different temperatures are negative.The dissociation constants KD do not show a systematic dependence on the electron donating abilities of the substituents in the aryl groups.Small differences between the UV-vis absorption spectra of unpaired and paired ions were used to confirm the conductimetrically determined values of KD. - Key words: Carbocations / Electrochemistry / Ionisation / Spectroscopy, Visible / Thermodynamics
- Schneider, Reinhard,Mayr, Herbert,Plesch, Peter H.
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p. 1369 - 1374
(2007/10/02)
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- Protonation of p-Methoxybenzhydryl Cations; a New Series of Indicators for Superacid Acidity Measurements by Nuclear Magnetic Resonance Spectroscopy
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The behaviour of (p-substituted phenyl)(p-methoxyphenyl)methanol derivatives dissolved in superacid mixtures (HF, HFSO3, or CF3SO3H with various proportions of SbF5) has been studied by n.m.r. spectroscopy.Increasing the SbF5 concentration causes drastic changes in chemical shifts due to stable O-protonation of the methoxy group in the highest acidity media.By using these bases as indicators for superacid acidity measurements we have shown that the acidity of these three systems does not increase as fast as previously claimed, and also that the acidity of the CF3SO3H-SbF5 system remains lower than that of the HFSO3-SbF5 system in the 0-50percent SbF5 range.
- Touiti, Dominique,Jost, Roland,Sommer, Jean
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p. 1793 - 1798
(2007/10/02)
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