- Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles
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Site-selective chlorination of benzylic C–H bonds is achieved using a CuICl/bis(oxazoline) catalyst with N-fluorobenzenesulfonimide as the oxidant and KCl as a chloride source. This method exhibits higher benzylic selectivity, relative to estab
- Lopez, Marco A.,Buss, Joshua A.,Stahl, Shannon S.
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supporting information
p. 597 - 601
(2022/01/20)
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- Ferric(III) Chloride Catalyzed Halogenation Reaction of Alcohols and Carboxylic Acids Using α,α-Dichlorodiphenylmethane
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A new method for chlorination of alcohols and carboxylic acids, using α,α-dichlorodiphenylmethane as the chlorinating agent and FeCl3 as the catalyst, was developed. The method enables conversions of various alcohols and carboxylic acids to their corresponding alkyl and acyl chlorides in high yields under mild conditions. Particulary interesting is the observation that the respective alkyl bromides and iodides can be generated from alcohols when either LiBr or LiI are present in the reaction mixtures.
- Lee, Chang-Hee,Lee, Soo-Min,Min, Byul-Hana,Kim, Dong-Su,Jun, Chul-Ho
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supporting information
p. 2468 - 2471
(2018/04/25)
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- Silica gel-mediated hydrohalogenation of unactivated alkenes using hydrohalogenic acids under organic solvent-free conditions
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Silica gel-mediated hydrochlorination of unactivated alkenes using 35% hydrochloric acid under organic solvent-free conditions proceeded to give the corresponding chlorides in good yields. Hydrobromination or hydriodination using 47% hydrobromic acid or 55% hydriodic acid afforded the corresponding halides, respectively. Silica gel could be recycled five times without any significant loss of activities.
- Tanemura, Kiyoshi
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supporting information
p. 4293 - 4298
(2018/11/10)
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- Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency
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A practical method for the nucleophilic substitution (SN) of alcohols furnishing alkyl chlorides, bromides, and iodides under stereochemical inversion in high catalytic efficacy is introduced. The fusion of diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride as a reagent allows notable turnover numbers up to 100. Moreover, the use of plain acetyl chloride as a stoichiometric promotor in an invertive SN-type transformation is demonstrated for the first time. The operationally straightforward protocol exhibits high levels of stereoselectivity and scalability and tolerates a variety of functional groups.
- Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
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supporting information
p. 2980 - 2983
(2018/05/28)
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- A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions
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A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.
- Huy, Peter H.,Filbrich, Isabel
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supporting information
p. 7410 - 7416
(2018/04/30)
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- METHOD OF CONVERTING ALCOHOL TO HALIDE
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The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.
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Page/Page column 50; 144; 148; 149
(2017/01/02)
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- Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
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A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.
- Huy, Peter H.,Motsch, Sebastian,Kappler, Sarah M.
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supporting information
p. 10145 - 10149
(2016/08/16)
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- Aromatic cation activation of alcohols: Conversion to alkyl chlorides using dichlorodiphenylcyclopropene
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(Chemical Equation Presented) A novel paradigm for the activation of alcohols toward nucleophilic displacement via formation of cyclopropenium ethers is described. The conversion of a range of alcohol substrates to the corresponding alkyl chlorides occurs rapidly upon treatment with 3,3-dichloro-1,2-diphenylcyclopropene. 1H NMR data support the intermediacy of a cyclopropenium intermediate, and the reaction is demonstrated to proceed primarily via the SN2 mechanism for 1-phenylethanol. A total of 12 examples of substrate scope are provided.
- Kelly, Brendan D.,Lambert, Tristan H.
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supporting information; experimental part
p. 13930 - 13931
(2009/12/25)
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- Phenyl versus alkyl migration in the fragmentation of alkoxychlorocarbenes
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Phenyl versus methyl (alkyl) group migration is assessed in the fragmentations of neophyloxychlorocarbene, 2,2-diphenylpropyloxychlorocarbene, and 1-phenylcyclopropylmethoxychlorocarbene. Rate constants and activation parameters of the fragmentations are also reported.
- Moss, Robert A.,Fu, Xiaolin
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p. 235 - 237
(2007/10/03)
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- OXIDATIVE DECARBOXYLATION OF CARBOXYLIC ACIDS BY IRON PORPHYRIN - IODOSYLBENZENE SYSTEM
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An iodosylbenzene - iron tetraarylporphyrin catalyst system decarboxylated α-aryl carboxylic acids and α,α,α-trisubstituted acetic acids efficiently to give the corresponding alcohol and carbonyl derivatives.
- Komuro, Masakatsu,Nagatsu, Yoshio,Higuchi, Tsunehiko,Hirobe, Masaaki
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p. 4949 - 4952
(2007/10/02)
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- Borderline between E1 and E2 Mechanisms. Bimolecular Base-Promoted Elimination via Ion Pairs Competing with Concerted E2 Elimination
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The solvolysis of 2-chloro-2-methyl-1-phenylpropane (1) in methanol or in 25 vol percent acetonitrile in water at 25 deg C yields substitution product 2 (ether or alcohol) and the two elimination products 3 and 4.The olefin fraction in the aqueous solution does not increase significantly in the presence of 0.75 M sodium hydroxide.In methanol, on the other hand, the fraction of 3 and 4, the ratio /, and the rate of disappearance of 1 increase with methoxide ion concentration.The kinetic isotope effects (k12H + k13H + k14H)/(k12d2 + k13d2 +k14d2) = 1.41 and 1.42, measured for the solvolysis of the dideuterated analogue d2-1 in water/acetonitrile and in methanol, respectively, are too large to be secondary effects on a rate-limiting ionization step, but they suggest reaction via a reversibly formed carbocationic intermediate.The solvolysis of the hexadeuterated analogue d6-1 exhibits "normal" secondary kinetic isotope effects, (k12H + k13H + k14H)/(k12d6 + k13d6 + k14d6) = 1.79 and 1.81 in water/acetonitrile and methanol, respectively.The presence of 2 M NaOMe increases the isotope effect for d2-1 to 2.4 but decreases the effect for d6-1 to 1.35.These results indicate that 3 is formed by a parallel methoxide-promoted one-step concerted rout (E2) and that such a route is not significant for the formation of 4.The isotope effect for the E2 reaction is estimated as kH/kd2 = 4.9 (on the basis of the assumption that the elimination product ratio / for the carbocationic route is not affected by MeO(1-)).
- Thibblin, Alf
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p. 5412 - 5416
(2007/10/02)
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- Kinetics of the 1,2-Migration of Carbon-Centered Groups in 2-Substituted 2,2-Dimethylethyl Radicals
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The rearrangements RCMe2CH2. -> RCH2C.Me2 (kr) (R = Ph, Me3CCC, Me3CC=O, and NC) have been studied over a range of temperatures by product analyses with use of the common competiting reaction RCMe2CH2. + CCl4 -> RCMe2CH2Cl + CCl3. (kCl).For R = H2C=CH the rearrangement was so fast that only the rearranged chloride, RCH2CMe2Cl, was produced.All these rearrangements occur via a 3-membered cyclic intermediate radical (or transition state).Various considerations led to the following Arrhenius equation for chlorine abstraction: log (kCl/M-1 s-1)=(8.14 +/- 0.42)-(5.52 +/- 0.63)/τ, where τ=2.3RT kcal/mol, and this equation is used to calculate Arrhenius parameters for migration of all but the H2C=CH group.Comparison of these parameters with those already available from kinetic EPR measurements leads to a choice of preferred Arrhenius parameters for all five rearrangements.The cyano group had an unexpectedly low mobility while the pivaloyl group underwent a surprisingly rapid 1,2-shift.Migratory aptitudes increase along the series R = NC C r at 25 deg C = 0.9, 93, 762, 1.7*105, and 1.0 * 107 s-1, respectively.The preferred pre-exponential factors all lie in the range 1010.9 - 1012.0, while the activation energies vary from 16.4 kcal/mol for R = NC to 5.7 kcal/mol for R = H2C=CH.These results are discussed in relation to the results of thermochemical kinetic calculations and to earlier work on the 1,2-migration of unsaturated groups in radicals.
- Lindsay, D. A.,Lusztyk, J.,Ingold, K. U.
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p. 7087 - 7093
(2007/10/02)
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- Catalytic Replacement of Unactivated Alkane Carbon-Hydrogen Bonds with Carbon-X Bonds (X = Nitrogen, Oxygen, Chlorine, Bromine, or Iodine). Coupling of Intermolecular Hydrocarbon Activation by MnIIITPPX Complexes with Phase-Transfer Catalysis
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A simple system has been devised to facilitate the first processes for the catalytic replacement of unactivated alkane C-H bonds with C-X bonds, X = nitrogen and iodine.The system also enables alkane C-H bonds to be replaced by C-X bonds, X = chlorine, bromine, and oxygen.The system is composed of two liquid phases and the oxidant iodosylbenzene (iodosobenzene).The alkane substrate, the MnIIITPPX catalyst, and the organic solvent (dichloromethane, chlorobenzene, or other aromatic hydrocarbon) constitute one phase, a saturated aqueous solution of the sodium salt of the anion to be incorporated into the alkane, NaX, X = N3(1-), NCO(1-), I(1-), Br(1-), or Cl(1-), constitutes the second phase, and the sparingly soluble oxidant iodosylbenzene constitutes a third phase.When the two liquid phases and the oxidant iodosylbenzene are stirred under an inert atmosphere, both RX and ROH products are produced catalytically based on MnTPP and in reasonable yield based on iodosylbenzene.The MnTPP moiety functions as a catalyst for C-H bond cleavage and for phase transfer of X(1-) from the aqueous phase to the organic phase where the functionalization chemistry takes place.The oxidant hypochlorite can be used in place of, but is less effective than, iodosylbenzene, and the oxidants hydrogen peroxide, periodate, and persulfate are ineffective.Product distributions obtained from the oxidation of cyclohexane, isobutane, 2,3-dimethylbutane, and tert-butylbenzene are most consistent with a product-determining step that involves transfer of X from manganese to a free alkyl radical intermediate.
- Hill, Craig L.,Smegal, John A.,Henly, Timothy J.
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p. 3277 - 3281
(2007/10/02)
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- Hydrocarbon Functionalization by the (Iodosylbenzene)manganese(IV) Porphyrin Complexes from the (Tetraphenylporphinato)manganese(III)-Iodosylbenzene Catalytic Hydrocarbon Oxidation System. Mechanism and Reaction Chemistry
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The two types of complexes isolated from the reaction of (tetraphenylporphinato)manganese(III) derivatives, XMnIIITPP, with iodosylbenzene - IVTPP(OIPh)>2O, 1, X = Cl- or Br-, and IVTPP>2O, 2, X = N3- - are capable of oxidizing alkane substrates in good yields at room temperature.Several lines of evidence establish the intermediacy of free alkyl radicals in the reactions of 1 and 2 with alkanes.Oxygen exchange with water in both the iodosyl (Mn-O-I) and μ-oxo (Mn-O-Mn) moieties of 1 suggests the formation of oxo manganese porphyrin complexes from these moieties.Hydrogen abstraction from the alkane substrate by an oxo manganese porphyrin intermediate is postulated to be mechanism for reaction of 1 and 2 with alkanes.Observation of a monomeric manganese(IV) porphyrin intermediate by EPR spectroscopy during the reactions of 1 with alkanes is consistent with the formation of a hydroxymanganese(IV) porphyrin complex resulting from substrate hydrogen abstraction by an oxo intermediate.The formation of RX product from oxidation of RH by 1 has been determined to result from ligand-transfer oxidation of free alkyl radicals by the porphyrin complexes in solution.Through competition reactions and time-dependent product formation studies, ligand-transfer oxidation by XMnIIITPP was found to be the major pathway for RX production.Observation of MnIITPP by EPR spectroscopy during the reactions of 1 with alkanes supports this conclusion.Formation of ROH product may result from ligand-transfer oxidation of free radicals or from the collapse of an intermediate caged radical pair.The mechanism of ROH product formation in the caged radical pair is postulated to be an outer-sphere electron-transfer process due to the expected slow rate of inner-sphere ligand transfer for the high-spin d3 hydroxymanganese(IV) porphyrin complex.Thus the ability of the substrate radical to undergo electron-transfer oxidation determines the ratio of radicals that undergo cage escape to give free radicals to radicals that undergo oxidation and subsequent formation of alcohol product in the caged species.Studies with tertiary substrates support these conclusions.
- Smegal, John A.,Hill, Craig L.
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p. 3515 - 3521
(2007/10/02)
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- TEMPERATURE AND MATRIX EFFECTS ON MULTIPLICITY-SPECIFICITY AND C-H INSERTION SELECTIVITY IN REACTION OF PHENYLCARBENE
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Photochemical studies of phenyldiazomethane in 2-chloropropane as a function of temperature reveal that C-Cl insertion of singlet phenylcarbene is dominant at lower temperature as long as the solvent is liquid, but primary C-H insertion becomes near-exclusive in a rigid matrix, suggesting that two kinds of matrix effect are operating.
- Tomioka, Hideo,Suzuki, Shinji,Izawa, Yasuji
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p. 293 - 296
(2007/10/02)
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