- Enantioselective "clip-cycle" synthesis of di-, tri- and spiro-substituted tetrahydropyrans
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ω-Unsaturated alcohols were "clipped"via alkene metathesis to a thioester activating group, which was followed by a chiral phosphoric acid catalyzed intramolecular oxa-Michael cyclization to yield tetrahydropyrans and spiro-tetrahydropyrans with excellent
- Alomari, Khadra,Sai Pavan Chakravarthy,Duchadeau, Bastien,Ermanis, Kristaps,Clarke, Paul A.
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supporting information
p. 1181 - 1185
(2022/02/19)
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- Tuning the Reactivity of Alkoxyl Radicals from Cyclization to 1,2-Silyl Transfer: Stereoselective Synthesis of β-Substituted Cycloalcohols
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Herein, we report a radical strategy for diastereoselective construction of β-substituted cyclopentanols and cyclobutanols. The success of the reaction is attributed to the favorable radical 1,2-silyl transfer over the cyclization of alkoxy radicals to the olefins. The reaction shows broad substrate scope and wide functional-group tolerance. The synthetic potential of the methodology was demonstrated in the gram scale reaction and facile synthesis of various spiro compounds.
- He, Xingyi,Shen, Xiao,Zhang, Zeguo,Zhao, Yunlong
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supporting information
(2022/03/17)
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- Enantio- and Regioselective Palladium(II)-Catalyzed Dioxygenation of (Aza-)Alkenols
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An oxidative Pd-catalyzed intra-intermolecular dioxygenation of (aza-)alkenols has been reported, with total regioselectivity. To study the stereoselectivity, different chiral ligands as well as different hypervalent-iodine compounds have been compared. I
- Giofrè, Sabrina,Molteni, Letizia,Nava, Donatella,Lo Presti, Leonardo,Beccalli, Egle Maria
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supporting information
p. 21723 - 21727
(2021/09/08)
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- Rhodium-Catalyzed Cyclization of O,ω-Unsaturated Alkoxyamines: Formation of Oxygen-Containing Heterocycles
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O,ω-Unsaturated N-tosyl alkoxyamines undergo unexpected RhIII-catalyzed intramolecular cyclization by oxyamination to produce oxygen-containing heterocycles. Mechanistic studies show that an aziridine intermediate seems to be responsible for the formation of the heterocycles, possibly via a RhV species.
- Escudero, Julien,Bellosta, Véronique,Cossy, Janine
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supporting information
p. 574 - 578
(2018/02/21)
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- Ring-opening of cyclic ethers with carbon-carbon bond formation by Grignard reagents
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The ring-opening of cyclic ethers with concomitant C-C bond formation was studied with a number of Grignard reagents. The transformation was performed in a sealed vial by heating to ~160 °C in an aluminum block or at 180 °C in a microwave oven. Good yields of the product alcohols were obtained with allyl- and benzylmagnesium halides when the ether was tetrahydrofuran or 3,3-dimethyloxetane. Lower yields were obtained with substituted tetrahydrofurans while no ring-opening was observed with tetrahydropyran. Only highly reactive allyl and benzyl Grignard reagents participated in the transformation while no reaction occurred with other alkylmagnesium halides.
- Christensen, Stig Holden,Holm, Torkil,Madsen, Robert
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p. 4942 - 4946
(2014/07/07)
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- BISMACROKYCLIC COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
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The present invention discloses compounds of formula (Ia) or (Ib) or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequent
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Page/Page column 92
(2011/05/06)
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- Synthesis of vaniprevir (MK-7009): Lactamization to prepare a 22-membered macrocycle
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Development of a practical synthesis of MK-7009, a 22-membered macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ri
- Song, Zhiguo J.,Tellers, David M.,Journet, Michel,Kuethe, Jeffrey T.,Lieberman, David,Humphrey, Guy,Zhang, Fei,Peng, Zhihui,Waters, Marjorie S.,Zewge, Daniel,Nolting, Andrew,Zhao, Dalian,Reamer, Robert A.,Dormer, Peter G.,Belyk, Kevin M.,Davies, Ian W.,Devine, Paul N.,Tschaen, David M.
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experimental part
p. 7804 - 7815
(2011/12/14)
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- MASKED CARBOXYLATE NEOPENTYL SULFONYL ESTER CYCLIZATION RELEASE PRODRUGS OF ACAMPROSATE, COMPOSITIONS THEREOF, AND METHODS OF USE
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Masked carboxylate neopentyl sulfonyl ester prodrugs of acamprosate, pharmaceutical compositions comprising such prodrugs, and methods of using such prodrugs and compositions thereof for treating diseases are disclosed. In particular, acamprosate prodrugs
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Page/Page column 54
(2009/04/24)
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- Cobalt-catalysed hydrovinylation as the key step in a short synthesis of moenocinol
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A regio- and chemoselective cobalt(i)-catalysed 1,4-hydrovinylation reaction is the key step in the straightforward and convergent synthesis of moenocinol, the aglycone of moenomycin A.
- Hilt, Gerhard,Treutwein, Jonas
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supporting information; experimental part
p. 1395 - 1397
(2009/07/10)
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- A relay ring-closing metathesis synthesis of dihydrooxasilines, precursors of (Z)-lodo olefins
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(Chemical Equation Presented) A convenient Grubbs II metathesis provides dihydrooxasilines by relay RCM (RRCM). Dihydrooxasilines undergo ring opening to give Z-vinyl silanes. These can then be converted to Z-vinyl iodides. This sequence provides a short,
- Xie, Qiuzhe,Denton, Richard W.,Parker, Kathlyn A.
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supporting information; experimental part
p. 5345 - 5348
(2009/06/06)
-
- HCV NS3 protease inhibitors
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The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.
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Page/Page column 77
(2008/06/13)
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- Remarkable phosphine-effect on the intramolecular aldol reactions of unsaturated 1,5-diketones: Highly regioselective synthesis of cross-conjugated dienones
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We report a phosphine-mediated intramolecular aldol cyclization of unsaturated diketones that proceeds with extremely high levels of regioselectivity for the cross-conjugated bicyclic dienone products. The sense of regioselectivity observed in this reacti
- Thalji, Reema K.,Roush, William R.
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p. 16778 - 16779
(2007/10/03)
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- Mechanism of Reaction of Geminal Dihalides with Lithium Aluminum Hydride. Evidence for Single Electron Transfer as the Major Reaction Pathway
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The reactions of a sterically hindered geminal dichloride 4a and the corresponding diiodide 4b with LiAlH4 (LAH) were found to involve an electron-transfer mechanism.Whereas the monochloro analog of 4a (8) is inert toward LAH, 4a was more reactive.Observation of radical-derived products in the reaction of 4a with LAH indicates that the presence of two chlorine atoms on the same carbon atom results in a favorable reduction potential for 4a, as compared to 8.These results show that LAH can function as a one-electron donor toward geminal dichlorides.It was found that the diiodo analog 4b is more reactive toward LAH than 4a due to the inherent favorable reduction potentials of alkyl iodides compared to chlorides.The reactivity of 4b toward LAH was also found to be greater than that of the monoiodo analog (1b) in keeping with the more favorable reduction potential of the diiodide (4b) compared to the monoiodide (1b).The rates of cyclization of the corresponding haloalkyl radicals generated from 4a and 4b were also determined and were found to be 7.4E5/s for the chloroalkyl and 5.5E5/s for the iodoalkyl radical at 25 deg C.The formation of small amounts of the carbene-derived product, 5, in the reactions of both 4a and 4b with LAH appeared to be preceded by a radical intermediate.
- Ashby, E. C.,Deshpande, Abhay K.
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p. 3798 - 3805
(2007/10/02)
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- Mechanism of Reaction of Geminal Dihalides with Magnesium. Evidence for the Formation of Carbenes from Radical Precursors. The Similarity in Reactions of Geminal Dihalides with Magnesium and LiAlH4
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The geminal dihalides, 6,6-dichloro-5,5-dimethyl-1-hexene (2a) and 6,6-diiodo-5,5-dimethyl-1-hexene (2b) were allowed to react with Rieke activated magnesium (Mg*) in THF at 25 deg C.Both radical and carbene intermediates were identified by product analyses, by radical trapping experiments using DCPH and THF-d8, and by selective experiments in which isolated intermediates were shown to form the predicted products.Although carbene products predominated over radical products when the dichloride was allowed to react with Mg*, radical products predominated when the diiodide was allowed to react with Mg*.Evidence is presented that indicates that the carbene intermediate arises from a radical precursor.A mechanistic scheme (Scheme 5) is presented that is consistent with all of the observed data.A comparison of the reactions of 2b with Mg* and 2b with LiAlH4 shows that most of the products are common in both reactions thereby providing further evidence for LiAlH4 as a one-electron donor, as is known behavior of Mg*.
- Ashby, E. C.,Deshpande, Abhay K.,Doctorovich, Fabio
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p. 6223 - 6232
(2007/10/02)
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- Competing Radical, Carbanion, and Carbene Pathways in the Reactions of Hindered Primary Alkyl Halides with Lithium Dialkylamides
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A variety of methods were utilized to study the mechanism of reaction of 6-iodo-5,5-dimethyl-1-hexene and its bromo, chloro, and tosylate derivatives with LDA and several other lithium dialkylamides.In the reaction of 6-iodo-5,5-dimethyl-1-hexene with LDA in THF, radical, carbanion, and carbene pathways occured simultaneously.However, when the corresponding bromide was allowed to react with LDA, the radical pathway was minor and when the corresponding chloride or tosylate was allowed to react with LDA, no evidence for radical products was observed.This is the first time that competing radical, carbanion, and carbene pathways have been detected in the reaction of a primary alkyl halide with any nucleophile.
- Ashby, E. C.,Park, B.,Patil, G. S.,Gadru, K.,Gurumurthy, R.
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p. 424 - 437
(2007/10/02)
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- Single Electron Transfer Mechanism in the Reaction of 1,3-Dithianyllithium and Alkyl Iodides
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The reaction between 2-lithio-1,3-dithiane and optically active (R)-2-iodooctane was found to proceed with complete inversion of configuration.This result suggests that the SN2 (rather than single electron transfer (SET)) mechanism is the preferred pathway for reaction between dithianyllithium and unhindered alkyl halides.When the neopentyl-type radical probe 5,5-dimethyl-6-iodo-1-hexene was used as the substrate halide, 6-11percent cyclized alkylated product was obtained.This result suggests that when the SN2 pathway is blocked, SET mechanisms become operative to some extent, at least with iodide as the halogen.The reaction of dithianyllithium and (R)-2-iodooctane and 5,5-dimethyl-6-iodo-1-hexene, with hexane as the solvent, proceeds under heterogeneous conditions to bring about complete racemization of the respective iodide.These results demonstrate for the first time that 2-lithio-1,3-dithiane can act as electron donor in reactions initiated by electron transfer to alkyl iodides.
- Juaristi, Eusebio,Jimenez-Vazquez, Hugo A.
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p. 1623 - 1630
(2007/10/02)
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- γ-Lithioalkoxides via Reductive Lithiation of Oxetanes by Aromatic Radical Anions
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Oxetanes are cleaved at 0 deg C in tetrahydrofuran by lithium 4,4'-di-tert-butylbiphenylide, giving lithium γ-lithioalkoxides which can provide 2-substituted tetrahydrofurans by trapping with aldehydes and ketones followed by acid cyclization of the resulting 1,4-diols; the cuprates of these dianions undergo conjugate addition and nucleophilic substitution reactions.
- Mudryk, Boguslaw,Cohen, Theodore
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p. 5657 - 5659
(2007/10/02)
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- Occurrence of Electron Transfer in the Reduction of Organic Halides by LiAlH4 and AlH3
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A variety of methods have been utilized to detect the occurrence of a single electron transfer pathway in the reduction of alkyl halides by LiAlH4 and AlH3, i.e., (1) product studies of reduction of cyclizable alkyl halides containing the 5-hexenyl group, (2) trapping of intermediate radicals by dicyclohexylphosphine and other trapping agents, (3) direct EPR observation of the trityl radical in the reduction of trityl bromide, and (4) stereochemical studies of the reduction of secondary halides by lithium aluminum deuteride.The extent of electron transfer was found to be a function of the solvent, the substrate, the leaving group, and the hydride reagent.For alkyl iodides, and to a lesser extent bromides, electron transfer was found to be the major reaction pathway; however, no evidence for electron transfer was found for the corresponding chlorides or tosylates.Reduction of (+)-2-octyl iodide by LiAlD4 was found to be much less stereospecific than the corresponding reduction of bromide, chloride, or tosylate, indicating intermediate radical formation in the reduction of the secondary iodide.
- Ashby, E. C.,DePriest, R. N.,Goel, A. B.,Wenderoth, Bernd,Pham, Tung N.
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p. 3545 - 3556
(2007/10/02)
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- Mechanistic Probes of the Hydride-Transfer Process in the Reduced Nicotinamide Adenine Dinucleotide Dependent Alcohol Dehydrogenase Reactions
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NADH-dependent alcohol dehydrogenase reductions of several chemically based radical-probe molecules proceed without any indication of the radical anion intermediates.
- Chung, Sung-Kee,Park, Seung-Un
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p. 3197 - 3198
(2007/10/02)
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