- The Silicon-Hydrogen Exchange Reaction: Catalytic Kinetic Resolution of 2-Substituted Cyclic Ketones
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We have recently reported the strong and confined, chiral acid-catalyzed asymmetric 'silicon-hydrogen exchange reaction'. One aspect of this transformation is that it enables access to enantiopure enol silanes in a tautomerizing σ-bond metathesis, via deprotosilylation of ketones with allyl silanes as the silicon source. However, until today, this reaction has not been applied to racemic, 2-substituted, cyclic ketones. We show here that these important substrates readily undergo a highly enantioselective kinetic resolution furnishing the corresponding kinetically preferred enol silanes. Mechanistic studies suggest the fascinating possibility of advancing the process to a dynamic kinetic resolution.
- List, Benjamin,Zhang, Pinglu,Zhou, Hui
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supporting information
p. 1953 - 1956
(2021/11/17)
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- Palladium-catalyzed asymmetric hydrogenation of 2-aryl cyclic ketones for the synthesis oftranscycloalkanols through dynamic kinetic resolution under acidic conditions
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The first efficient palladium-catalyzed asymmetric hydrogenation of 2-aryl cyclic ketones has been described through dynamic kinetic resolution under acidic conditions, providing a facile access to chiraltranscycloalkanol derivatives with excellent enantioselectivities.
- Li, Xiang,Zhao, Zi-Biao,Chen, Mu-Wang,Wu, Bo,Wang, Han,Yu, Chang-Bin,Zhou, Yong-Gui
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supporting information
p. 5815 - 5818
(2020/06/03)
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- Asymmetric Induction via a Helically Chiral Anion: Enantioselective Pentacarboxycyclopentadiene Br?nsted Acid-Catalyzed Inverse-Electron-Demand Diels-Alder Cycloaddition of Oxocarbenium Ions
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An enantioselective catalytic inverse-electron-demand Diels-Alder reaction of salicylaldehyde acetal-derived oxocarbenium ions and vinyl ethers to generate 2,4-dioxychromanes is described. Chiral pentacarboxycyclopentadiene (PCCP) acids are found to be effective for a variety of substrates. Computational and X-ray crystallographic analyses support the unique hypothesis that an anion with point-chirality-induced helical chirality dictates the absolute sense of stereochemistry in this reaction.
- Gheewala, Chirag D.,Hirschi, Jennifer S.,Lee, Wai-Hang,Paley, Daniel W.,Vetticatt, Mathew J.,Lambert, Tristan H.
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supporting information
p. 3523 - 3527
(2018/03/21)
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- Construction of a chiral quaternary carbon center by catalytic asymmetric alkylation of 2-arylcyclohexanones under phase-transfer conditions
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In this paper, we present an asymmetric alkylation of modified 2-arylcyclohexanones that employs a novel chiral ammonium bromide as a phase-transfer catalyst and an achiral auxiliary as a controller to improve the enantioselectivity to afford optically enriched products having a chiral quaternary carbon center.
- Kano, Taichi,Hayashi, Yumi,Maruoka, Keiji
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supporting information
p. 7134 - 7137
(2013/06/27)
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- The 2-(2-Azidoethyl)cycloalkanone strategy for bridged amides and medium-sized cyclic amine derivatives in the Aubé-Schmidt reaction
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2-(2-Azidoethyl)cycloalkanones afford bridged lactams in the Aubé-Schmidt reaction, sometimes in excellent yield, and solvolysis yields derivatives of medium-ring amines. Attempts to divert the Schmidt reaction with an arene-mediated fragmentation of the normal Schmidt intermediate have led to an initial example. Georg Thieme Verlag Stuttgart.
- Macleod, Fraser,Lang, Stuart,Murphy, John A.
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supporting information; experimental part
p. 529 - 534
(2010/10/02)
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- Discovery of N-(2-aryl-cyclohexyl) substituted spiropiperidines as a novel class of GlyT1 inhibitors
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Screening of the Roche compound library led to the identification of cis-N-(2-phenyl-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform.
- Pinard, Emmanuel,Ceccarelli, Simona M.,Stalder, Henri,Alberati, Daniela
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p. 349 - 353
(2007/10/03)
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- TRIAZA-SPIROPIPERIDINE DERIVATIVES FOR USE AS GLYT-1 INHIBITORS IN THE TREATMENT OF NEUROLOGICAL AND NEUROPSYCHIATRIC DISORDERS
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The invention relates to compounds of the general formula (I), wherein A-A is -CH2-CH2-, -CH2-CH2-CH2-, -CH2-0- or -0-CH2-; x is hydrogen or hydroxy; R1 is aryl or heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, halogen or trifluoromethyl; R2 is aryl or heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, halogen or trifluoromethyl, or is lower alkyl, -(CH2)n--cycloalkyl, -(CH2)n-CF3, -(CH2)p-0-lower alkyl, -(CH2)1,2-phenyl, optionally substituted by halogen, lower alkyl, lower alkoxy or trifluoromethyl, or is -(CH2)p-NRR", wherein W and R" form together with the N-atom a heterocyclic ring, selected from the group consisting of piperidine, morpholine, thiomorpholine or 1, I-dioxo thiomorpholine; R3, R4 are independently from each other hydrogen, lower alkyl, phenyl or benzyl; R5 is hydrogen, lower alkyl or benzyl; R6 is hydrogen or lower alkyl; n is 0, 1 or 2; and p is 2 or 3; and to pharmaceutically acceptable acid addition salts thereof for the treatment of psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.
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Page/Page column 30
(2010/02/11)
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- Substituted 1-aminobutan-3-ol compounds
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Substituted 1-aminobutane-3-ol compounds, methods for producing them, pharmaceutical compounds containing them, and the use of substituted 1-aminobutane-3-ol compounds for producing pharmaceutical compounds.
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- Enantioselective protonation of silyl enol ethers and ketene disilyl acetals with Lewis acid-assisted chiral Bronsted acids: Reaction scope and mechanistic insights
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Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding α-aryl ketones and α-arylcarboxylic acids, respectively, with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing α-halocarbonyl compounds (up to 91% ee). DFT calculations on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the absolute stereochemistry of the products.
- Nakamura, Shingo,Kaneeda, Masanobu,Ishihara, Kazuaki,Yamamoto, Hisashi
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p. 8120 - 8130
(2007/10/03)
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- α-iodocycloalkenones: Synthesis of (±)-epibatidine
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A synthesis of the non-opiate analgesic alkaloid epibatidine was achieved in 13 steps and 13% Overall yield starting from 1,3-cyclohexadiene using in a key step a modified Stille coupling reaction on an α- iodocyclohexenone.
- Sirisoma, Nilantha S.,Johnson, Carl R.
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p. 2059 - 2062
(2007/10/03)
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- The stereochemistry of hippurate alkylation
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Alkylation of the hippurate esters of trans 2-(p-substituted phenyl)cyclohexanol with benzyl bromide affords phenylalanine derivatives in high chemical yield. The reaction stereoselectivity varies from 20 to >98% depending on the aromatic group in the cyclohexyl auxiliary. A model that correctly predicts the sense of the induction is proposed.
- McIntosh, John M.,Kiser, E. Jay,Tian, Zhigang
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p. 147 - 151
(2007/10/03)
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- Asymmetric synthesis of CDP840 by Jacobsen epoxidation. An unusual syn selective reduction of an epoxide
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An asymmetric synthesis of the PDE IV inhibitor, CDP840 (3) is reported. The absolute stereochemistry was controlled by a Jacobsen epoxidation of the Z triaryl olefin 8 (89% ee) or the E triaryl olefin 9 (48% ee). The disparate results in stereocontrol were interpreted in terms of the 'skewed side-on approach model' proposed by Jacobsen. LiBH4 · BH3 reduction of the epoxides was found to proceed with retention of configuration.
- Lynch,Choi,Churchill,Volante,Reamer,Ball
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p. 9223 - 9228
(2007/10/03)
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- Inhibitors of acyl CoA:cholesterol acyltransferase
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Conformational restriction of previously disclosed acyclic diphenylethyl)diphenylacetamides led to the discovery of several potent inhibitors of acyl CoA:cholesterol acyltransferase (ACAT). cis-[2-(4- Hydroxyphenyl)-1-indanyl]diphenylacetamide (4a) was the most potent ACAT inhibitor identified (IC50 = 0.04 μM in an in vitro rat hepatic microsomal ACAT assay, ED50 = 0.72 mg/kg/day in cholesterol-fed hamsters).
- Vaccaro, Wayne,Amore, Cindy,Berger, Joel,Burrier, Robert,Clader, John,Davis, Harry,Domalski, Martin,Fevig, Tom,Salisbury, Brian,Sher, Rosy
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p. 1704 - 1719
(2007/10/03)
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- Enzymatic resolution of trans-2-arylcyclohexan-1-ols using crude chicken liver esterase (CCLE) as biocatalyst
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Homochiral trans-2-arylcyclohexan-1-ols were synthesized via crude chicken liver esterase (CCLE) mediated enantioselective hydrolysis of the corresponding racemic acetates.
- Basavaiah,Rao
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p. 223 - 234
(2007/10/02)
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- Enantioselective synthesis using crude enzymes
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Chiral trans-2-aryloxycyclohexan-1-ols, trans-2-alkoxycyclohexan-1-ols, trans-2-arylcyclohexan-1-ols, homoallyl alcohols, 1-aryl-1-alkanols, 1,2-diphenylethane-1,2-diol are prepared in high optical purities via enantioselective hydrolysis of acetates of the corresponding racemic alcohols using crude enzymes such as pig liver acetone powder (PLAP), goat liver acetone powder (GLAP), chicken liver acetone powder (CLAP) and bovine liver acetone powder (BLAP).
- Basavaiah, Deevi,Krishna, Peddinti Rama
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p. 131 - 134
(2007/10/02)
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- BORON FLUORIDE PROMOTED OPENING OF EPOXIDES BY ORGANOCOPPER AND CUPRATE REAGENTS
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In the presence of BF3 the reaction rate of organocopper and cuprate reagents with poorly reactive epoxides is dramatically enhanced.Lithium organocuprates are the best choice among the various organocopper and cuprate reagents tested.Even the dimesityl cyanocuprate is able to react with cyclohexene oxide in excellent yield.No products of cationic rearrangements are observed.The reaction with various epoxides shows a complete stereochemical (pure anti opening) and regiochemical control (attack on the less hindered side of the epoxide).
- Alexakis, A.,Jachiet, D.,Normant, J. F.
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p. 5607 - 5620
(2007/10/02)
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- Determination of Configurations by the Aid of Sterically Corresponding Epoxides. VIII. Glycidic Nitriles. I. Synthesis of 4-Aryl-1-oxaspiro(2,5)octane-2-nitriles and 4-Aryl-1-oxaspiro(2,5)octane-2-carboxylic Acid Methyl Esters
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The condensation of 2-aryl-cyclohexan-1-ones (1-5) with ClCH2CN or ClCH2CO2CH3 at 80 deg C in the presence of NaH and in dimethoxyethane yields the corresponding glycidic nitriles and the glycidic esters, respectively.The conformation and the preferred configuration of the two isomeric 1-oxaspiro-octane derivatives (12A and 12B) formed have been determined by 1H-n.m.r. spectroscopy.Some earlier results from BOEKELHEIDE and SCHILLING and from SCHWARTZMAN and WOODS have been corrected.
- Fischer, F.,Palitzsch, P.
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p. 561 - 573
(2007/10/02)
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- The Stability of Allylic and Vinylic Deuterium Atoms During the Lithium/Ammonia Reduction of Some Styrenoid Systems
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Reduction of 2-(p-methoxyphenyl)cyclohexan-1-one (8) with lithium aluminium deuteride followed by acetylation gave trans-1-acetoxy-2-(p-methoxyphenyl)(1-2H1)cyclohexane (10b).Base-catalysed deuteration of 2-(p-methoxyphenyl)cyclohexan-1-one (8) afforded t
- Collins, David J.,Molinski, Tadeusz F.,Sjoevall, Jan
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p. 361 - 370
(2007/10/02)
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