- Enantioselective Synthesis of Indolines, Benzodihydrothiophenes, and Indanes by C?H Insertion of Donor/Donor Carbenes
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We employ a single catalyst/oxidant system to enable the asymmetric syntheses of indolines, benzodihydrothiophenes, and indanes by C?H insertion of donor/donor carbenes. This methodology enables the rapid construction of densely substituted five-membered rings that form the core of many drug targets and natural products. Furthermore, oxidation of hydrazones to the corresponding diazo compounds proceeds in situ, enabling a relatively facile one- or two-pot protocol in which isolation of potentially explosive diazo alkanes is avoided. Regioselectivity studies were performed to determine the impact of sterics and electronics in donor/donor metal carbene C?H insertions to form indolines. This methodology was applied to a variety of substrates in high yield, diastereomeric, and enantiomeric ratios and to the synthesis of a patented indane estrogen receptor agonist with anti-cancer activity.
- Souza, Lucas W.,Squitieri, Richard A.,Dimirjian, Christine A.,Hodur, Blanka M.,Nickerson, Leslie A.,Penrod, Corinne N.,Cordova, Jesus,Fettinger, James C.,Shaw, Jared T.
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supporting information
p. 15213 - 15216
(2018/10/31)
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- Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent
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An alternative method for forming sulfonates through hypervalent iodine(III) reagent-mediated oxidation of sodium sulfinates has been developed. This transformation involves trapping reactive sulfonium species using alcohols. With additional optimization of the reaction conditions, the method appears extendable to other nucleophiles such as electron-rich aromatic systems or cyclic ethers through a ring opening pathway.
- Deruer, Elsa,Hamel, Vincent,Blais, Samuel,Canesi, Sylvain
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supporting information
p. 1203 - 1207
(2018/06/04)
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- Cobalt-Catalyzed Carbonylative Cross-Coupling of Alkyl Tosylates and Dienes: Stereospecific Synthesis of Dienones at Low Pressure
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Despite advances in organometallic cross-coupling of alkyl electrophiles, there are few stereoselective reactions of chiral, nonracemic substrates. Herein we report a stereospecific carbonylative coupling of alkyl tosylates and dienes producing enantioenriched dienones. This catalytic process proceeds under low pressure and mild conditions using a simple cobalt catalyst and extends to diverse tosylate and diene coupling partners. The transformation constitutes a unique, convergent approach to the asymmetric synthesis of valuable carbonyl compounds from easily accessed starting materials.
- Sargent, Brendon T.,Alexanian, Erik J.
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supporting information
p. 12438 - 12440
(2017/09/25)
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- Cobalt-Catalyzed Silylcarbonylation of Unactivated Secondary Alkyl Tosylates at Low Pressure
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A catalytic preparation of silyl enol ethers from unactivated secondary alkyl tosylates is reported. An inexpensive cobalt catalyst is used under mild conditions with low pressures of carbon monoxide. Nucleophilic, anionic cobalt carbonyls facilitate the catalytic activation of a range of alkyl tosylates. The silylcarbonylation offers a practical approach to synthetically valuable silyl enol ethers from simple starting materials.
- Roque Pena, Joan E.,Alexanian, Erik J.
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supporting information
p. 4413 - 4415
(2017/09/11)
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- NOVEL ETHER LINKED COMPOUNDS AND IMPROVED TREATMENTS FOR CARDIAC AND CARDIOVASCULAR DISEASE
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A compound of Formula (I), and its pharmaceutically acceptable salt or salts and physiologically hydrolysable derivatives in free form or salt form: wherein R1 is independently selected from F, CI, Br, CN, NH2, OH, CHO, COOH, oxo, C1-4alkyl, C1-4alkoxy, CONH2 (optionally mono- or di-substituted by C1-4alkyl) and SO2NH2, R2 is independently selected from C1-6allkyl substituted by R3 wherein the C1-6alkyl chain optionally comprises one or two heteroatoms select from O; R3 is selected from aryl, C3-6cycloalkyl, C3-6heterocyclyl and C3-6heteroaryl, wherein the heterocyclyl and heteroaryl rings are nitrogen containing; and wherein R3 is optonally substituted by one or more groups selected from R1; n1 is zero or an integer from 1 to 2; n2 is an integer from 1 to 2; and the sum of n1 and 2 is less than or equal to 2; R5 is selected from any group defined for R1 and R2; R6a and R6b are independently selected from H or C1-4alkyl; R7 is independently selected from F, CI, Br, CN, NH2, OH, CHO, COOH, oxo, C1-4alkyl, C1-4alkoxy, CONH2 (optionally mono- or di-substituted by C1-4alkyl) and SO2NH2, Q1, Q2 and Q3 are independently selected from H or any group defined for R1 and R2; or Q1 and Q2 or Q2 and Q3 together form a C5-6heteroaryl or C5-6heterocylclic ring; optionally containing one or two heteroatoms selected from N and O optionally substituted by any group selected from R5; Z is selected from linear C2-3 alkylene; X3 is O; X4 is selected from aryl, a 9-10 membered heteroaryl ring or a 9-10 membered heterocyclic ring, wherein the heteroaryl and heterocyclic rings contain one or more heteroatoms selected from N, and optionally additionally O, and wherein X4 is optionally substituted by one or two oxo moieties and is optionally substituted by one or more groups selected from R7; with the proviso that: (i) when X4 is phenyl then Q1 and Q2 or Q2 and Q3-together form an optionally substituted heteroaryl or heterocylclic ring as defined above; and (ii) when Q1, Q2 and Q3 are independently selected from H or any group defined for R1 and R2 then X4 is not phenyl except when R2 is C1-5alkyl substituted by R3 wherein R3 is C3-6heterocyclyl as defined above.
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Page/Page column 31
(2012/08/27)
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- EQUILIBRATIVE NUCLEOSIDE TRANSPORTER ENT1 INHIBITORS
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The present invention is related to novel compounds of formula (I) having equilibrative nucleoside transporter ENTl inhibiting properties, pharmaceutical compositions comprising these compounds, chemical processes for preparing these compounds and their use in the treatment of diseases linked to the inhibition of ENTl receptors in animals, in particular humans.
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Page/Page column 45
(2009/06/27)
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- Solvent-free and selective tosylation of alcohols and phenols with p-toluenesulfonyl chloride by heteropolyacids as highly efficient catalysts
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Tosylation of some alcohols and phenols has been directly carried out with p-toluenesulfonyl chloride using heterodoxy acids (H3PW 12O40, H3PMo12O40, A 3PW12O40, and AlPMo12O40) as catalysts in the absence of solvent. We found that heteropoly acids AlPW12O40 and AlPMo 12O40 were effective catalysts for the tosylation of alcohols and phenols. In the case of aliphatic alcohols, secondary alcohols undergo tosylation chemoselectively in the presence of primary hydroxyl groups. This new method consistently has the advantage of excellent yields and short reaction time.
- Fazaeli, Razieh,Tangestaninejad, Shahram,Aliyan, Hamid
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p. 812 - 818
(2007/10/03)
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- 1-[(INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES
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The present invention relates to 1-[(indol-3-yl)carbonyl]piperazine derivative according to the general formula (I), wherein R represents 1-4 substituents independently selected from H, (C1-4)alkyl (optionally substituted with halogen), (C sub
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- Silver(I) oxide-mediated facile and practical sulfonylation of alcohols
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Primary and secondary alcohols were efficiently sulfonylated in the presence of silver(I) oxide and potassium iodide in dichloromethane. The sulfonylation occurs under mild, neutral reaction conditions. The ease of isolation of the final product presents a marked advantage over the known methodologies.
- Bouzide, Abderrahim,LeBerre, Nicolas,Sauvé, Gilles
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p. 8781 - 8783
(2007/10/03)
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- 19-nor steroids having a thiocarbonated chain in position 11beta, their preparation process and the intermediates of this process, and the intermediates of this process, their use as medicaments and compositions
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Compounds of formula (I), wherein R17and R′17are such that: either R17and R′17together form ketone, hydrazono, oxime or methylene, or R17is hydroxyl, hydroxymethyl or acyloxy and R′17is hydrogen, alkyl or optionally substitued alkenyl or alkynyl; R3is hydrogen or alkyl; R16is hydrogen, halogen or alkyl; m is 0, 1 or 2; X, Y and Z are such that: X is methylene, arylene or arylenoxy bonded to the steroid by a carbon atom; Y is a saturated or unsaturated straight or branched aliphatic chain which is optionally interrupted by oxygen; and Z is aryl, arylalkyl or straight or branched alkyl; addition salts thereof, a preparation method therefor, medicinal uses thereof, compositions containing said compounds, and resulting novel intermediates.
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- Montmorillonite clay catalyzed tosylation of alcohols and selective monotosylation of diols with p-toluenesulfonic acid: An enviro-economic route
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An enviro-economic route for tosylation of alcohols and selective monotosylation of diols in good yield directly using p-toluenesulfonic acid together with metal-exchanged montmorillonite instead of p-toluenesulfonyl chloride or p-toluenesulfonic anhydrid
- Choudary, Boyapati M.,Chowdari, Naidu S.,Kantam, Mannepalli L.
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p. 7291 - 7298
(2007/10/03)
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- Scope and utility of a new soluble copper catalyst [CuBr-LiSPh-LiBr-THF]: A comparison with other copper catalysts in their ability to couple one equivalent of a Grignard reagent with an alkyl sulfonate
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A mixture of equal amounts of CuBr-SMe2, LiBr, and LiSPh in THF at 0°C furnished a new soluble copper catalyst that was highly efficient at coupling primary, secondary, tertiary, aryl, vinyl, and allylic Grignard reagents to primary tosylates and primary Grignard reagents to secondary tosylates and mesylates, all with the use of only 1 equiv of Grignard reagent. The new catalyst was shown to be much more reactive than copper catalysts CuBr and Li2CuCl4 and more efficient in the transference of secondary and tertiary alkyl groups than lower order cuprates (Gilman reagents) and demonstrated more reactivity than the lower order cuprates with its ability to couple primary Grignard reagents to secondary sulfonates. The Grignard reagent/catalyst system was compatible with an ester functionalized tosylate, thus proving to be more chemoselective than a Grignard reagent without the catalyst. The catalyst exhibited good reactivity below room temperature, and with the addition of 6% v/v of HMPA to the catalyst solution, excellent yields of coupled product were obtained within a 25-67°C temperature range. 1H NMR demonstrated that the catalyst solution consisted of several species that most likely were composed of copper ligated with thiophenol, THF, and LiBr in aggregated forms.
- Burns, Dennis H.,Miller, Jeffrey D.,Chan, Ho-Kit,Delaney, Michael O.
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p. 2125 - 2133
(2007/10/03)
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- Process for the production of aniline derivatives
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Industrial process for the efficient production of aniline derivatives which are important intermediates for the manufacture of oxazolidinedione derivatives and tetrahydrophthalimide derivatives which are useful as active ingredients of herbicides. The process starts from 2,4-dihalo-5-aminophenol or bis(2,4-dihalo-5-aminophenyl)carbonate and selectively cycloalkylates or alkynylates the hydroxy group without protecting the amino group, whereby aniline derivatives having the cycloalkyloxy group or alkynyloxy group can be produced in high yield.
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- Solvent Effects on Solvolytic Reactivity. A Diagnostic Test for Neighboring-Group Assistance by ? Conjugation in Solvolysis Reactions
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The solvolysis rates of 13 arenesulfonates have been determined in mixtures of ethanol and water (the E-series solvents) and acetic acid and formic acid (the A-series solvents).The substrates studied include the following: neophyl (1), 2-adamantyl (2), neopentyl (3), and cyclooctyl (4) tosylates; cyclopropylcarbinyl pemsylate (5a) and tosylate (5b); exo-2-norbornyl tosylate (6); cyclobutylcarbinyl (7), cyclobutyl (8), and pinacolyl (9) brosylates; cyclopentyl (10), cyclohexyl (11), and 2-propyl (12) tosylates; and cyclopentylcarbinyl brosylate (13).Correlations of the rate data by eq 1 t(Y) = a + b log kt(neophyl-OTs)> showed that the various substrates responded differently to the examined solvent effects on the solvolytic reactivity.For compounds 2-4, linear correlations were obtained.For compounds 5-9, E-line, A-line dispersions were noted which diverged with increasing ionizing power; for compounds 10-12, parallel E-line, A-line dispersions were obtained; and for compound 13, an E-line, A-line dispersion was observed which converged with increasing ionizing power.Stastistical analyses of the rate data correlations confirmed the significance of the E or A classification of data.The results are interpreted in terms of differences in the involvement of solvent in the transition state for those solvolyses assisted by bridging from those assisted by C-C ? bond hyperconjugation.
- Roberts, Donald D.
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p. 2521 - 2526
(2007/10/02)
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- Enamines of 2,2-bis(ethylthio)ethanal: a convenient route to γ-keto crotonate derivatives
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A new α-oxoaldehyde reagent, 2,2-bis(ethylthio)ethanal 1, has been prepared in high yield from ethanedial.Alkylation of the potassium salt of the enamines of 1 with various alkylating agents followed by in situ hydrolysis of the intermediate imine afforded high yields of the alkylation products of 1.This new reagent was used in the synthesis of a chiral potential precursor of the macrocyclic fragment of cytochalasins A,B, and F, as well as in the syntheses of the physiologically active diolides pyrenophorin and norpyrenophorin.
- Bates, Gordon S.,Ramaswamy, S.
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p. 2466 - 2475
(2007/10/02)
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- A SIMPLE METHOD FOR TOSYLATION WITH INVERSION
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In this paper we describe a simple one-step procedure for tosylation with inversion, using zinc tosylate, diethylazodicarboxylate and triphenylphospine.
- Galynker, Igor,Still, W. Clark
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p. 4461 - 4464
(2007/10/02)
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- Nuclear Heptylation of Benzene and Naphthalene and Cyclopentylation of Toluene
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Thermal decomposition of 1-, 2-, 3- and 4-heptyltoluene-p-sulphonates in the presence of aromatic substrates like benzene or naphthalene at 130-35 deg, affords differently substituted α- and β-isomers in the case of naphthalene.Skeletal isomerisation of the alkyl group is observed where different isomeric 1-, 2-, 3- and 4-heptyl-aromatics are obtained.Also thermal decomposition of cyclopentylmethane sulphonate in the presence of toluene at 130-35 deg, furnishes the corresponding o-, m- and p-substituted toluenes.The isomers have been identified and estimated quantitatively by GLC.
- Badr, M. Z. A.,El-Naggar, G. M.,Aly, M. M.,Fahmy, A. M.
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p. 961 - 964
(2007/10/02)
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