- Preparation of highly optically active substituted 2,3-methanocinnamyl alcohols
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Cyclopropanation of a variety of substituted cinnamyl alcohols with Et2Zn and CH2I2 proceeded in the presence of a catalytic amount of (S)-2-(methanesulfonyl)amino-1-(p-toluenesulfonyl)amino-3-phenylpropane to afford the corresponding cyclopropylmethanols in excellent yields and with moderate to high enantioselectivity (51-86% ee). Highly enantiomerically enriched substituted 2,3-methanocinnamyl alcohols (84-97% ee) were obtained by conversion of the corresponding 2,3-methanocinnamyl alcohols produced in the enantioselective cyclopropanation to the 3,5-dinitrobenzoyl ester derivatives, followed by recrystallization and hydrolysis.
- Imai, Nobuyuki,Nomura, Tetsuro,Yamamoto, Shinya,Ninomiya, Yoshihiro,Nokami, Junzo
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- Asymmetric Simmons-Smith Cyclopropanation of E-Allylic Alcohols Using 1,1'-Bi-2-naphthol-3,3'-dicarboxamide as a Chiral Auxiliary
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N,N,N',N'-Tetraethyl-1,1'-bi-naphthol-3,3'-dicarboxamide (1b) was found to be an effective chiral auxiliary for asymmetric Simmons-Smith cyclopropanation and high enantioselectivity greater than 85percent ee was achieved in the reaction of E-allylic alcohols.
- Kitajima, Hiroshi,Aoki, Yuko,Ito, Katsuji,Katsuki, Tsutomu
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- Highly efficient asymmetric simmons-smith cyclopropanation promoted by chiral heteroorganic aziridinyl ligands
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Enantiomerically pure heteroorganic catalysts, bearing a hydroxy moiety, a stereogenic sulfinyl group, and a chiral aziridine moiety, have proved highly efficient in the asymmetric Simmons-Smith cyclopropanation of allylic alcohols, which generates the desired products in high yields (up to 95 %) and with ee values up to 94 %. The effect of the stereogenic centers at the sulfinyl sulfur atom and in the aziridine moiety on the stereochemical course of the title reaction is discussed. Combination at its best: Enantiomerically pure heteroorganic ligands, bearing a hydroxy moiety, a stereogenic sulfinyl group, and an enantiomeric aziridine moiety, have proved highly efficient in the asymmetric Simmons-Smith cyclopropanation of allylic alcohols, which generates the desired products in high yields (up to 95 %) and with ee values up to 94 %.
- Rachwalski, Michal,Kaczmarczyk, Sylwia,Lesniak, Stanislaw,Kielbasinski, Piotr
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- Catalytic enantioselective cyclopropanation with bis(halomethyl)zinc reagents. I. Optimization of reaction protocol
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The rate and selectivity of catalytic enantioselective cyclopropanation of cinnamyl alcohol utilizing bis-iodomethyl zinc and 4a/4b is greatly dependent on the order of addition of the reagents. The independent preformation of the ethylzinc cinnamyloxide and bis(iodomethyl)zinc was found to be crucial. The reaction displayed autocatalytic behavior which was shown to be due to the generation of zinc iodide.
- Denmark,Christenson,Coe,O'Connor
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- Catalytic, Enantioselective Cyclopropanation of Allylic Alcohols. Substrate Generality
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Catalytic, enantioselective cyclopropanation of a broad range of allylic alcohols and one homoallylic alcohol was carried out. The cyclopropanation reagent employed was bis(iodomethyl)zinc generated by the method of Furukawa, and the chiral promoter used (10 mol %) was the N,N-bis-(methanesulfonyl) derivative of (R,R)-1,2-diaminocyclohexane. Three experimental features were found to be critical for the rapid and selective cyclopropanation: (1) use of the ethylzinc alkoxide of the allylic alcohol as the substrate by prior deprotonation of the allylic alcohols by diethylzinc, (2) the formation of the zinc complex of the promoter by prior deprotonation of the bis-sulfonamide with diethylzinc, and (3) the use of added zinc iodide generated in situ from diethylzinc and iodine. The stereoselectivity of cyclopropanation was found to be independent of olefin geometry and worked well for substrates bearing both aliphatic and aromatic substituants at either or both 3-positions of the allylic alcohol. However, a methyl substituent on the 2-position of the allyl alcohol was not well tolerated and led to slow reactions and poor enantioselectivities. A rationale for the observed selectivities is proposed.
- Denmark, Scott E.,O'Connor, Stephen P.
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- Iodomethylzinc phosphates: Powerful reagents for the cyclopropanation of alkenes
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A new family of zinc carbenoids derived from phosphoric acids was developed and used in the cyclopropanation of allylic alcohols and ethers and also of unfunctionalized olefins. The use of the chiral phosphoric acid of a 3,3′-disubstituted BINOL leads to efficient stereocontrol, affording the cyclopropanes of allylic and homoallylic ethers with complete conversions and up to 93% ee. A catalytic version of this reaction using 10 mol % of the chiral phosphate reagent is also disclosed. Copyright
- Lacasse, Marie-Christine,Poulard, Cyril,Charette, Andre B.
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- Skeletally Tunable Seven-Membered-Ring Fused Pyrroles
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We describe a copper-mediated method that enables the synthesis of seven-membered-ring fused pyrroles (7-mrFPs). The protocol proceeds via an in situ spiro-intermediate ring expansion and tolerates a library of 7-mrFP derivatives with a broad range of functional groups in a simple step with tangible parameters and substrate adaptations. These rare 7-mrFPs are now accessible on a millimolar scale, and selected examples exhibit high antioxidant activity.
- Andreou, Dimitrios,Essien, Nsikak B.,Pubill-Ulldemolins, Cristina,Terzidis, Michael A.,Papadopoulos, Athanasios N.,Kostakis, George E.,Lykakis, Ioannis N.
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supporting information
p. 6685 - 6690
(2021/09/11)
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- FLUOROALKYL-OXADIAZOLES AND USES THEREOF
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Provided herein are compounds identified as inhibitors of HDAC6 activity that can be used to treat various diseases and disorders.
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Paragraph 00621-00622
(2021/06/26)
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- Donor-Acceptor Bicyclopropyls as 1,6-Zwitterionic Intermediates: Synthesis and Reactions with 4-Phenyl-1,2,4-triazoline-3,5-dione and Terminal Acetylenes
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The bicyclopropyl system activated by incorporation of donor and acceptor groups in the presence of Lewis acids was used as a synthetic equivalent of 1,6-zwitterions. Opening of both cyclopropane rings in 2′-aryl-1,1′-bicyclopropyl-2,2-dicarboxylates (D-A bicyclopropyl, ABCDs) in the presence of GaI3 + Bu4N+GaI4- results in 5-iodo-5-arylpent-2-enylmalonates as products of HI formal 1,6-addition to the bicyclopropyl system. The use of GaCl3 or GaBr3 as a Lewis acid and terminal aryl or alkyl acetylenes as 1,6-zwitterion interceptors allows the alkyl substituent to be grown to give the corresponding acyclic 7-chloro(bromo)-hepta-2,6-dienylmalonates. The reaction of ABCDs with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) catalyzed by Yb(OTf)3 also results in the opening of both cyclopropane rings. The reaction products are tetrahydropyridazine derivatives - (7,9-dioxo-1,6,8-triazabicyclo[4.3.0]non-3-en-2-ylmethyl)malonates - containing one more PTAD moiety in the malonyl group.
- Potapov, Konstantin V.,Denisov, Dmitry A.,Glushkova, Valeriia V.,Novikov, Roman A.,Tomilov, Yury V.
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p. 15562 - 15576
(2020/11/30)
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- Visible-Light Controlled Divergent Catalysis Using a Bench-Stable Cobalt(I) Hydride Complex
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While the use of visible light in conjunction with transition metal catalysis offers powerful opportunities to switch between on/-off states of catalytic activity, the next frontier would be the ability to switch the actual function of the catalyst and resulting products. Here we report such an example of multi-dimensional catalysis. Featuring an easily prepared, bench-stable cobalt(I) hydride complex in conjunction with pinacolborane, we can switch the reaction outcome between two widely employed transformations, olefin migration and hydroboration, with visible light as the trigger.
- Beltran, Frédéric,Bergamaschi, Enrico,Teskey, Christopher J.
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supporting information
p. 5180 - 5184
(2020/04/22)
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- Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides
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New protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX2). Use of a different halide on ZnX2 dictates the selectivity, wherein the NaH-ZnI2 system delivers alcohols and NaH-ZnCl2 gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH2)∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H?Zn?Cl)2 is the key species for the production of amines.
- Ong, Derek Yiren,Yen, Zhihao,Yoshii, Asami,Revillo Imbernon, Julia,Takita, Ryo,Chiba, Shunsuke
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p. 4992 - 4997
(2019/03/13)
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- 5,6,7,8-Tetrahydro-1,6-naphthyridine Derivatives as Potent HIV-1-Integrase-Allosteric-Site Inhibitors
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A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture. Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization of the integrase enzyme and are of significant interest as HIV-1-replication inhibitors. Structure-activity-relationship studies and rat pharmacokinetic studies of lead compounds are presented.
- Peese, Kevin M.,Allard, Christopher W.,Connolly, Timothy,Johnson, Barry L.,Li, Chen,Patel, Manoj,Sorensen, Margaret E.,Walker, Michael A.,Meanwell, Nicholas A.,McAuliffe, Brian,Minassian, Beatrice,Krystal, Mark,Parker, Dawn D.,Lewis, Hal A.,Kish, Kevin,Zhang, Ping,Nolte, Robert T.,Simmermacher, Jean,Jenkins, Susan,Cianci, Christopher,Naidu, B. Narasimhulu
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p. 1348 - 1361
(2019/02/24)
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- Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases
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Ene reductases from the Old Yellow Enzyme (OYE) family reduce the C=C double bond in α,β-unsaturated compounds bearing an electron-withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C?C bonds. α,β-Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two-electron-reduced enzyme cofactor FMN delivers a hydride to generate an enolate intermediate, which reacts with the internal electrophile. Single-site replacement of a crucial Tyr residue with a non-protic Phe or Trp favored the cyclization over the natural reduction reaction. The new transformation enabled the enantioselective synthesis of chiral cyclopropanes in up to >99 % ee.
- Heckenbichler, Kathrin,Schweiger, Anna,Brandner, Lea Alexandra,Binter, Alexandra,Toplak, Marina,Macheroux, Peter,Gruber, Karl,Breinbauer, Rolf
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p. 7240 - 7244
(2018/06/15)
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- Lewis Acid Catalyzed Annulation of Cyclopropane Carbaldehydes and Aryl Hydrazines: Construction of Tetrahydropyridazines and Application Toward a One-Pot Synthesis of Hexahydropyrrolo[1,2- b]pyridazines
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In this report, a facile synthesis of tetrahydropyridazines via a Lewis acid catalyzed annulation reaction of cyclopropane carbaldehydes and aryl hydrazines has been demonstrated. Moreover, the generated tetrahydropyridazine further participated in a cycloaddition reaction with donor-acceptor cyclopropanes to furnish hexahydropyrrolo[1,2-b]pyridazines. We also performed these two steps in one pot in a consecutive manner. In addition, a monodecarboxylation reaction of hexahydropyrrolo[1,2-b]pyridazine was achieved with a good yield.
- Dey, Raghunath,Kumar, Pankaj,Banerjee, Prabal
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p. 5438 - 5449
(2018/05/28)
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- Mild Ring-Opening 1,3-Hydroborations of Non-Activated Cyclopropanes
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The Brown hydroboration reaction, first reported in 1957, is the addition of B?H across an olefin in an anti-Markovnikov fashion. Here, we solved a long-standing problem on mild 1,3-hydroborations of non-activated cyclopropanes. A three-component system including cyclopropanes, boron halides, and hydrosilanes has been developed for borylative ring-opening of cyclopropanes following the anti-Markovnikov rule, under mild reaction conditions. Density functional theory (M06-2X) calculations show that the preferred pathway involves a cationic boron intermediate which is quenched by hydride transfer from the silane.
- Wang, Di,Xue, Xiao-Song,Houk, Kendall N.,Shi, Zhuangzhi
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p. 16861 - 16865
(2018/11/27)
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- Benzofuran-7-alkylamine compounds and applications thereof
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The inventor designs and synthesizes benzofuran-7-alkylamine compounds with a novel structure. The test results show that most of the disclosed benzofuran-7-alkylamine compounds have a strong activity on inhibiting the synthesis of golden yellow pigment, and some compounds have an extremely strong inhibiting activity on pigments of drug resistant bacteria (S.aureus USA400 MW2, USA300 LAC, Mu50), and prominently enhance the hydrogen peroxide killing and human blood killing in vitro. In vivo, for the animal model infected by sensitive strain (S.aureus Newman) and two drug resistant strains (S.aureus USA400 MW2, Mu50), the planting of bacteria in internal organs (kidney, heart, and liver) of mice is prominently reduced. The benzofuran-7-alkylamine compounds are advantageously used for producing novel anti-bacterium drugs.
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- Discovery of Potent Benzofuran-Derived Diapophytoene Desaturase (CrtN) Inhibitors with Enhanced Oral Bioavailability for the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections
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Blocking the staphyloxanthin biosynthesis process has emerged as a new promising antivirulence strategy. Previously, we first revealed that CrtN is a druggable target against infections caused by pigmented Staphylococcus aureus (S. aureus) and that naftifine was an effective CrtN inhibitor. Here, we identify a new type of benzofuran-derived CrtN inhibitor with submicromolar IC50 values that is based on the naftifine scaffold. The most potent analog, 5m, inhibits the pigment production of S. aureus Newman and three MRSA strains, with IC50 values of 0.38-5.45 nM, without any impact on the survival of four strains (up to 200 μM). Notably, compound 5m (1 μM) could significantly sensitize four strains to immune clearance and could effectively attenuate the virulence of three strains in vivo. Moreover, 5m was determined to be a weak antifungal reagent (MIC > 16 μg/mL). Combined with good oral bioavailability (F = 42.2%) and excellent safety profiles, these data demonstrate that 5m may be a good candidate for the treatment of MRSA infections.
- Wang, Youxin,Chen, Feifei,Di, Hongxia,Xu, Yong,Xiao, Qiang,Wang, Xuehai,Wei, Hanwen,Lu, Yanli,Zhang, Lingling,Zhu, Jin,Sheng, Chunquan,Lan, Lefu,Li, Jian
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p. 3215 - 3230
(2016/05/19)
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- Chiral recyclable fluorous disulfonamide ligand for catalytic enantioselective cyclopropanation of allylic alcohols
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Allylic alcohols reacted with Et2Zn and CH2I2 in the presence of a catalytic amount of fluorous disulfonamide 3a to afford the corresponding cyclopropylmethanols in 69%-quantitative yields with 49-85% ee. Recovery of the fluorous ligand 3a was readily performed from the reaction mixture by the fluorous solid-phase extraction (FSPE), and the recovered 3a could be reused without a significant loss of the catalytic activity and enantioselectivity.
- Kawashima, Yuya,Ezawa, Tetsuya,Yamamura, Mai,Harada, Taisuke,Noguchi, Takuya,Miura, Tsuyoshi,Imai, Nobuyuki
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p. 8585 - 8592
(2016/01/25)
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- Enantioselective syn and anti homocrotylation of aldehydes: Application to the formal synthesis of spongidepsin
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Whereas crotylboration has been a useful method for synthesis of stereochemically complex products, we have shown that homocrotylboration can be achieved with cyclopropanated crotylation reagents, and that the stereoselectivity of the reaction can be predicted by analogous models. This paper presents a full account of this work, including the first examples of asymmetric anti homocrotylation. The scope of this reaction is demonstrated with highly enantioselective homocrotylation of both aliphatic and aromatic aldehydes, as well as double diastereoselection studies. An application of the synthesis of the marine natural product spongidepsin is presented, as well as streamlined syntheses of homocrotylation reagents.
- Lin, Hongkun,Tian, Leiming,Krauss, Isaac J.
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p. 13176 - 13182
(2015/10/28)
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- Copper-catalyzed regio- and stereoselective intermolecular three-component oxyarylation of allenes
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A copper(II)-catalyzed intermolecular three-component oxyarylation of allenes using arylboronic acids as a carbon source and TEMPO as an oxygen source is described. The reaction proceeded under mild conditions with high regio- and stereoselectivity and functional group tolerance. A plausible reaction mechanism is proposed, involving carbocupration of allenes, homolysis of the intervening allylcopper(II), and a radical TEMPO trap.
- Itoh, Taisuke,Shimizu, Yohei,Kanai, Motomu
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p. 2736 - 2739
(2014/06/09)
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- Improved zinc-catalyzed simmons-smith reaction: Access to various 1,2,3-trisubstituted cyclopropanes
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The Simmons-Smith reaction of zinc carbenoids with alkenes is a powerful method to access cyclopropanes containing various substitution patterns. This work exploits the high reactivity of aryldiazomethanes toward zinc halides to generate aryl-substituted carbenoids catalytically. These carbenoids are able to cyclopropanate various alkenes diastereoselectively, including unfunctionalized substrates such as styrenes. The zinc catalyst can be modified to tolerate the use of free allylic alcohols.
- Levesque, Eric,Goudreau, Sebastien R.,Charette, Andre B.
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p. 1490 - 1493
(2014/04/03)
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- Asymmetric syntheses of pharmaceuticals containing a cyclopropane moiety using catalytic asymmetric Simmons-Smith reactions of allylalcohols: Syntheses of optically active tranylcypromine and milnacipran
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Asymmetric synthesis of tranylcypromine was achieved using an enantioselective Simmons-Smith cyclopropanation catalyzed by a simple disulfonamide derived from an -amino acid. The optically active milnacipran was also synthesized by porcine pancreas lipase-catalyzed selective monoacylation of the C4-hydroxy group in (Z)-2-phenylbut-2-ene-1,4-diol and the enantioselective Simmons-Smith cyclopropanation as the key steps.
- Ishizuka, Yuki,Fujimori, Hirohisa,Noguchi, Takuya,Kawasaki, Masashi,Kishida, Mari,Nagai, Takuya,Imai, Nobuyuki,Kirihara, Masayuki
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p. 1311 - 1313
(2013/10/22)
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- Mechanistic investigation of oxidative Mannich reaction with tert-butyl hydroperoxide. the role of transition metal salt
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A general mechanism is proposed for transition metal-catalyzed oxidative Mannich reactions of N,N-dialkylanilines with tert-butyl hydroperoxide (TBHP) as the oxidant. The mechanism consists of a rate-determining single electron transfer (SET) that is uniform from 4-methoxy- to 4-cyano-N,N-dimethylanilines. The tert-butylperoxy radical is the major oxidant in the rate-determining SET step that is followed by competing backward SET and irreversible heterolytic cleavage of the carbon-hydrogen bond at the α-position to nitrogen. A second SET completes the conversion of N,N-dimethylaniline to an iminium ion that is subsequently trapped by the nucleophilic solvent or the oxidant prior to formation of the Mannich adduct. The general role of Rh2(cap) 4, RuCl2(PPh3)3, CuBr, FeCl 3, and Co(OAc)2 in N,N-dialkylaniline oxidations by T-HYDRO is to initiate the conversion of TBHP to tert-butylperoxy radicals. A second pathway, involving O2 as the oxidant, exists for copper, iron, and cobalt salts. Results from linear free-energy relationship (LFER) analyses, kinetic and product isotope effects (KIE and PIE), and radical trap experiments of N,N-dimethylaniline oxidation by T-HYDRO in the presence of transition metal catalysts are discussed. Kinetic studies of the oxidative Mannich reaction in methanol and toluene are also reported.
- Ratnikov, Maxim O.,Doyle, Michael P.
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supporting information
p. 1549 - 1557
(2013/03/14)
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- Silver-promoted, palladium-catalyzed direct arylation of cyclopropanes: Facile access to spiro 3,3′-cyclopropyl oxindoles
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The Pd-catalyzed, Ag(I)-mediated intramolecular direct arylation of cyclopropane C-H bonds is described. Various spiro 3,3′-cyclopropyl oxindoles can be obtained in good to excellent yields from easily accessible 2-bromoanilides. The kinetic isotope effect was determined and epimerization studies were conducted, suggesting that the formation of a putative Pd-enolate is not operative and that the reaction proceeds via a C-H arylation pathway.
- Ladd, Carolyn L.,Sustac Roman, Daniela,Charette, André B.
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p. 1350 - 1353
(2013/05/09)
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- Conformational restriction approach to β-Secretase (BACE1) inhibitors: Effect of a cyclopropane ring to induce an alternative binding mode
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Improvement of a drugs binding activity using the conformational restriction approach with sp3 hybridized carbon is becoming a key strategy in drug discovery. We applied this approach to BACE1 inhibitors and designed four stereoisomeric cyclopropane compounds in which the ethylene linker of a known amidine-type inhibitor 2 was replaced with chiral cyclopropane rings. The synthesis and biologic evaluation of these compounds revealed that the cis-(1S,2R) isomer 6 exhibited the most potent BACE1 inhibitory activity among them. X-ray structure analysis of the complex of 6 and BACE1 revealed that its unique binding mode is due to the apparent CH-π interaction between the rigid cyclopropane ring and the Tyr71 side chain. A derivatization study using 6 as a lead molecule led to the development of highly potent inhibitors in which the structure-activity relationship as well as the binding mode of the compounds clearly differ from those of known amidine-type inhibitors.
- Yonezawa, Shuji,Higashino, Kenichi,Tanaka, Yoshikazu,Nakano, Toru,Yamamoto, Takahiko,Yamakawa, Hidekuni,Muto, Chie,Hosono, Motoko,Hattori, Kazunari,Yutsudo, Takashi,Sakagami, Masahiro,Takemoto, Hiroshi,Iwamoto, Hideo,Kondo, Yutaka,Togame, Hiroko,Arisawa, Mitsuhiro,Shuto, Satoshi
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p. 8838 - 8858,21
(2020/09/16)
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- Highly stereoselective Ru(ii)-Pheox catalyzed asymmetric cyclopropanation of terminal olefins with succinimidyl diazoacetate
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The Ru(ii)-Pheox complex is an efficient catalyst for the intermolecular cyclopropanation of various terminal olefins with succinimidyl diazoacetate. This catalytic system can perform under mild conditions, and the desired cyclopropane products are obtain
- Chanthamath, Soda,Phomkeona, Kesiny,Shibatomi, Kazutaka,Iwasa, Seiji
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supporting information; experimental part
p. 7750 - 7752
(2012/09/21)
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- Synthesis of highly functionalized cyclohexenone rings: Rhodium-catalyzed 1,3-acyloxy migration and subsequent [5+1] cycloaddition
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Lead Rh-ole: Highly substituted cyclohexenones were prepared from cyclopropyl-substituted propargyl esters by using a [{Rh(CO)2Cl} 2] catalyst. This metal catalyst promoted the 1,3-acyloxy migration of propargyl esters and a subsequent [5+1] cycloaddition of the resulting allenylcyclopropanes in the presence of CO with high regioselectivity.
- Shu, Dongxu,Li, Xiaoxun,Zhang, Min,Robichaux, Patrick J.,Tang, Weiping
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supporting information; scheme or table
p. 1346 - 1349
(2011/04/22)
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- Alkenyl β-d-galactopyranoside derivatives as efficient chiral templates in stereoselective cyclopropanation and epoxidation reactions
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The synthesis of a wide range of alkenyl 4,6-O-(S)-benzylidene-β-d-galactopyranosides is described. The cyclopropanation and epoxidation reactions of these compounds were developed. Cyclopropanation reactions took place with high stereoselectivity giving diastereomeric excesses of up to 100%. As a part of our aim in studying hydroxyl-directed reactions, their epoxidation with m-CPBA was carried out. High diastereomeric excesses (80-100%) were obtained when the hydroxyl group at C-2 of the auxiliary was unprotected. The β-d-galactopyranoside moiety constitutes as an interesting auxiliary, due to its efficient chirality transfer capability as well as providing a way to obtain a variety of glycolipid derivatives.
- Vega-Perez, Jose M.,Perinan, Ignacio,Palo-Nieto, Carlos,Vega-Holm, Margarita,Iglesias-Guerra, Fernando
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experimental part
p. 81 - 95
(2010/04/06)
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- In situ generation of zinc carbenoids from diazo compounds and zinc salts: Asymmetric synthesis of 1,2,3-substituted cyclopropanes
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(Chemical Equation Presented) The first enantioselective cyclopropanation of alkenes using zinc carbenoids generated in situ from diazo compounds and zinc salts is reported. This new method allows the highly enantioand diastereoselective synthesis of 1,2,
- Goudreau, Sebastien R.,Charette, Andre B.
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supporting information; experimental part
p. 15633 - 15635
(2010/01/29)
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- Mechanistic studies on au(I)-catalyzed [3,3]-sigmatropic rearrangements using cyclopropane probes
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A comparative study of the Au(I)-catalyzed [3,3]-sigmatropic rearrangement of propargylic esters and propargyl vinyl ethers is described. Stereochemically defined cyclopropanes are employed as mechanistic probes to provide new synthetic and theoretical data concerning the reversibility of this type of rearrangement. Factors controlling the structure-reactivity relationship of Au(I)-coordinated allenes have been examined, therebyallowing for controlled access to orthogonal reactivity.
- Mauleon, Pablo,Krinsky, Jamin L.,Toste, F. Dean
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supporting information; experimental part
p. 4513 - 4520
(2009/09/30)
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- The use of 1,2-O-isopropylidene-α-d-xylofuranose as a chiral auxiliary in asymmetric cyclopropanation reactions
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The stereoselective synthesis of cyclopropylmethylidene acetals derived from 1,2-O-isopropylidene-d-xylofuranose, as a chiral auxiliary, is described. The Simmons-Smith cyclopropanation reaction of the corresponding alkenylidene derivatives with CH2
- Vega-Perez, Jose M.,Perinan, Ignacio,Iglesias-Guerra, Fernando
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experimental part
p. 1065 - 1072
(2009/09/30)
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- Kinetics of oxidation of benzphetamine by compounds I of cytochrome P4502B4 and its mutants
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Cytochromes P450 are ubiquitous heme-containing enzymes that catalyze a wide range of reactions in nature including many oxidation reactions. The active oxidant species in P450 enzymes are widely thought to be iron(IV)-oxo porphyrin radical cations, terme
- Sheng, Xin,Zhang, Haoming,Im, Sang-Choul,Horner, John H.,Waskell, Lucy,et al.
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supporting information; experimental part
p. 2971 - 2976
(2009/09/05)
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- Catalytic enantioselective cyclopropanation of allylic alcohols using recyclable fluorous disulfonamide ligand
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Cyclopropanation of allylic alcohols with Et2Zn and CH2I2 in the presence of a catalytic amount of fluorous disulfonamide 3 afforded the corresponding cyclopropylmethanols in 69-96% yield with 49-83% ee. The fluorous ligand 3 was readily recovered from the reaction mixture by the fluorous solid-phase extraction (FSPE) and could be reused without a significant loss of the catalytic activity and enantioselectivity.
- Miura, Tsuyoshi,Itoh, Keisuke,Yasaku, Yumi,Koyata, Naka,Murakami, Yasuoki,Imai, Nobuyuki
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p. 5813 - 5815
(2008/12/22)
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- Asymmetric Simmons-Smith reaction of allylic alcohols with Al Lewis acid/N Lewis base bifunctional Al(salalen) catalyst
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(Chemical Presented) Three angles: A highly enantioselective Simmons-Smith reaction of trans-disubstituted allylic alcohols was achieved by using a catalytic amount of an Al(salalen) complex at room temperature (see scheme).
- Shitama, Hiroaki,Katsuki, Tsutomu
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p. 2450 - 2453
(2008/12/23)
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- Stereoselective cyclopropanation of unsaturated acetals, using carbohydrates with d-gluco, l-rhamno and d-xylo configurations as chiral auxiliaries
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The stereoselective synthesis of (2-phenylcyclopropyl)methylidene acetals of sugar derivatives from methyl d-glucopyranoside, dodecyl N-acetyl-2-amino-2-deoxy-d-glucopyranoside, 1,2-O-isopropylidene-d-glucofuranose, methyl l-rhamnopyranoside and 1,2-O-isopropylidene-d-xylofuranose, as a chiral auxiliary, is described. The cyclopropanation reaction of the corresponding alkenylidene derivatives with CH2I2/ZnEt2 took place with different stereoselectivity, depending on the configuration on the acetal carbon, the size of the acetal ring, the sugar configuration, the protecting group of the hydroxyl groups of the sugar and the substitution of the unsaturated system. The stereochemistry of the new stereogenic centres was then determined by acid hydrolysis of the cyclopropane moiety of the chiral auxiliary, which was also recovered.
- Vega-Perez, Jose M.,Perinan, Ignacio,Vega, Margarita,Iglesias-Guerra, Fernando
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p. 1720 - 1729
(2008/12/20)
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- Kinetic Enzymatic Resolution of Cyclopropane Derivatives
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The kinetic enzymatic resolution of various cyclopropane derivatives was systematically investigated. The study focused on synthetically useful cyclopropylmethanols (e.g., 18a/j or 19a/j) as well as some rarely investigated cyclopropanols (e.g., 24/25 or 27). The combination of enantioselective catalytic or diastereoselective synthesis of enantiomerically enriched compounds with enzymatic approaches ultimately led to the most convenient route to enantiomerically pure starting materials. Again, this was especially proven for the synthesis of cyclopropanols 18a/j and 19a/j. Key to the successful investigation was to rigorously establish an analytical tool for the analysis of enantiomeric composition of reaction mixtures.
- Pietruszka, Joerg,Rieche, Anja C. M.,Wilhelm, Thorsten,Witt, Andreas
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p. 1273 - 1286
(2007/10/03)
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- Construction of a cis-Cyclopropane via Reductive Radical Decarboxylation. Enantioselective Synthesis of cis- and trans-1-Arylpiperazyl-2-phenylcyclopropanes Designed as Antidopaminergic Agents
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(1S,2S)-, (1S,2R)-, and (1R,2S)-1-(2,4-Dimethylphenyl)piperazyl-2-phenylcyclopropane (2a, 3, and ent-3, respectively), which were designed as conformationally restricted analogues of haloperidol (1), a clinically effective antipsychotic agent, were synthe
- Yamaguchi, Kazuya,Kazuta, Yuji,Abe, Hiroshi,Matsuda, Akira,Shuto, Satoshi
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p. 9255 - 9262
(2007/10/03)
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- Catalytic asymmetric cyclopropanation of allylic alcohols with titanium-TADDOLate: Scope of the cyclopropanation reaction
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A substoichiometric amount of titanium-TADDOLate complex was effective at catalyzing the cyclopropanation reaction of allylic alcohols in the presence 1 equiv of bis(iodomethyl) zinc. After initial optimization of the catalyst structure, excellent yields and enantiomeric ratios were obtained for 3-aryl- or 3-heteroaryl-substituted allylic alcohols (up to 97:3). Alkyl-substituted allylic alcohols gave modest yields and enantiomeric ratios (up to 87:13) but these compare favorably with those observed with other substoichiometric chiral ligands. The full synthetic scope of the reaction is presented in this paper.
- Charette,Molinaro,Brochu
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p. 12168 - 12175
(2007/10/03)
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- Highly enantioselective cyclopropanation of styrenes and diazoacetates catalyzed by 3-oxobutylideneaminatocobalt(II) complexes, part 1. Designs of cobalt complex catalysts and the effects of donating ligands
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Highly enantioselective cyclopropanation of styrene derivatives and diazoacetates was effectively catalyzed by reasonably designed 3-oxobutylideneaminatocobalt(II) complexes, whose ligands were prepared from 1,2-dimesitylethyl-enediamine and alkyl 3-oxobutanoates. The steric demand of the diamine unit of the complexes seriously influenced the enantioselectivity, and the ester groups on their side chains somewhat improved the trans-selectivity. Addition of a catalytic amount of N-methylimidazole significantly accelerated the reaction and enhanced the enantioselectivity due to its coordination to the center cobalt atom of the complex as an axial ligand. Alcoholic or aqueous alcoholic solvents were also effective particularly for the cyclopropanation of 1-substituted 1-phenylethylenes to achieve high enantioselectivity in aqueous methanol.
- Ikeno, Taketo,Sato, Mitsuo,Sekino, Hiroyuki,Nishizuka, Asae,Yamada, Tohru
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p. 2139 - 2150
(2007/10/03)
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- Stereoselective synthesis of novel cyclopropyl analogues of known cysteine protease inhibitors
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Efficient synthesis of two novel analogues of some known protease inhibitors, via the isosteric replacement of oxirane/aziridine moiety of the parent compounds by cyclopropane ring, is described.
- Ravi Kumar, Jalluri S.,Roy, Subho,Datta, Apurba
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p. 513 - 514
(2007/10/03)
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- Kinetic enzymatic resolution of cyclopropane derivatives
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The kinetic enzymatic resolution of cyclopropane acetates was systematically investigated utilizing 16 different hydrolases. Best results were obtained with hydrolyses in the presence of Candida antarctica B lipase.
- Pietruszka, J?rg,Wilhelm, Thorsten,Witt, Andreas
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p. 1981 - 1983
(2007/10/03)
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- Stereoselective Synthesis of a Key Precursor of Halicholactone and Neohalicholactone
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An efficient synthesis of a known precursor of halicholactone (1a) and neohalicholactone (1b) has been developed using the strategically functionalized key cyclopropane intermediate 2, which in turn has been synthesized via stereoselective cyclopropanation of trans-cinnamyl alcohol in the presence of the chiral dioxaborolane ligand 4. Elaboration of the above bifunctional cyclopropane to the target molecule was achieved in a relatively short reaction sequence and in good overall yield, representing a formal synthesis of the title compounds.
- Mohapatra, Debendra K.,Datta, Apurba
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p. 642 - 646
(2007/10/03)
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- Enantioselective cyclopropanation of allylic alcohols with dioxaborolane ligands: Scope and synthetic applications
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A very effective chiral controller has been found for the conversion of allylic alcohols into the corresponding enantiomerically enriched cyclopropanes using bis(iodomethyl)zinc. A variety of chiral, nonracemic cyclopropylmethanols could be obtained according to this method. This methodology was extended with success to the cyclopropanation of unconjugated and conjugated polyenes and homoallylic alcohols. The cyclopropanation of allylic carbamates has also been investigated with this system, but it was found that enantioenriched cyclopropylmethylamines are best prepared from enantioenriched cyclopropylmethanols.
- Charette, André B.,Juteau, Hélène,Lebel, Hélène,Molinaro, Carmela
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p. 11943 - 11952
(2007/10/03)
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- Solution and solid-state studies of a chiral zinc- sulfonamide complex relevant to enantioselective cyclopropanations
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A highly distorted tetrahedron formed by the four nitrogen atoms around zinc in the crystalline zinc-sulfonamide complex 1 may explain its catalytic activity in asymmetric cyclopropanations. The agent is formed by deprotonation of (R,R)-N,N'-cyclohexane-1,2-diyl)bis(n-butanesulfonamide) with diethylzinc and addition of 2,2'-bipyridyl.
- Denmark, Scott E.,O'Connor, Stephen P.,Wilson, Scott R.
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p. 1149 - 1151
(2007/10/03)
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- N,N,N′,N′-Tetraalkyl-2,2′-dihydroxy-1,1′- binaphthyl-3,3′-dicarboxamides: Novel Chiral Auxiliaries for Asymmetric Simons-Smith Cyclopropanation of Allylic Alcohols and for Asymmetric Diethylzinc Addition to Aldehydes
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The newly introduced tittle compounds were found to be efficient chiral auxiliaries for the asymmetric Simmons-Smith cyclopropanation of allylic alcohols and for asymmetric addition of diethylzinc to aldehydes. For example, Simmons- Smith cyclopropanation of cinnamyl alcohol in the presence of N,N,N′,N′-tetraethyl-2,2′-dihydroxy-1, 1′-binaphthyl-3, 3′-dicarboxamide (1b) proceeded with high enantioselectivity of 94% ee and addition of diethylzinc to benzaldehyde in the presence of N,N,N′,N′-tetraisopropyl-2,2′-dihydroxy-1,1′-binaphthyl- 3,3′-dicarboxamide (1e) proceeded with enantioselectivity of 99% ee. Although the reaction mechanism of these reactions is still nuclear, a monomeric seven-membered 2,2′-dihydroxy-1,1′-binaphthyl-3,3′-dicarboxamide (1)-Zn complex is considered to be an active species which catalyzes the above reactions, on the basis of NMR experiments.
- Kitajima, Hiroshi,Ito, Katsuji,Aoki, Yuko,Katsuki, Tsutomu
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p. 207 - 217
(2007/10/03)
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- A new chiral disulfonamide ligand derived from α-amino acid for catalytic enantioselective cyclopropanation
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A new disulfonamide prepared from α-amino acid in five steps catalyzed cyclopropanation of allylic alcohols with Et2Zn and CH2I2 to afford the corresponding cyclopropylmethanols in moderate to good enantioselectivites. In particular, the reaction of cinnamyl alcohol in the presence of a chiral disulfonamide 1k afforded an excellent enantioselectivity (85% ee).
- Imai, Nobuyuki,Sakamoto, Katsumasa,Maeda, Masahiro,Kouge, Kazushi,Yoshizane, Kenji,Nokami, Junzo
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p. 1423 - 1426
(2007/10/03)
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- Highly Enantioselective Intermolecular Cyclopropanation Catalyzed by Dirhodium(II) Tetrakis[3(S)-phthalimido-2-piperidinonate]: Solvent Dependency of the Enantioselection
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The enantioselectivity in cyclopropanations catalyzed by dirhodium(II) tetrakis[3(S)-phthalimido-2-piperidinonate] has been found to be substantially improved by employing ether as the rarely used solvent. Cyclopropanations of styrenes or 1,1-disubstituted alkenes with 2,4-dimethyl-3-pentyl diazoacetate in ether are promoted by this catalyst to afford the corresponding cyclopropane products in the highest levels of enantioselectivity (up to 98% ee) reported to date for the dirhodium(II)-catalyzed intermolecular cyclopropanation reactions.
- Kitagaki, Shinji,Matsuda, Hideo,Watanabe, Nobuhide,Hashimoto, Shun-Ichi
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p. 1171 - 1174
(2007/10/03)
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- Dirhodium(II)tetrakis[3(S)-phthalimido-2-piperidinonate]: A novel dirhodium(II) carboxamidate catalyst for asymmetric cyclopropanation
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Dirhodium(II) tetrakis[3(S)-phthalimido-2-piperidinonate] catalyzes cyclopropanation of α-methylstyrene with d-menthyl diazoacetate to give d-menthyl (1S,2S)-2-methyl-2-phenylcyclopropanecarboxylate of 90% de.
- Watanabe, Nobuhide,Matsuda, Hideo,Kuribayashi, Harumi,Hashimoto, Shun-Ichi
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p. 537 - 542
(2007/10/03)
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- Studies on the diastereoselective preparation of bis-cyclopropanes
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The identification of two natural products, FR-900848 and U-106305, has stimulated interest concerning the relationship between configurational isomerism, conformational isomerism, and biological activity of polycyclopropanes. Efforts to investigate the relationship between configurational and conformational isomerism through molecular modeling suggest that significantly different three-dimensional structures will result from unique primary structures. Any effort to address these issues demands that stereoselective methods for the preparation of polycyclopropanes be developed. We have investigated the application of zinc-carbenoid cyclopropanation in the presence of chiral dioxaboralanes to the preparation of eight stereochemically unique bicyclopropanes. The frans-vinylcyclopropane starting materials demonstrated very little substrate-induced stereoselectivity, while the cis-vinylcyclopropane demonstrates modest to excellent stereocontrol. A model for the substrate-based stereocontrol is proposed. We also used the spectroscopic data gathered in this investigation to probe the substrate-mediated stereocontrol in the rhodium(II)-catalyzed cyclopropanation of vinylcyclopropanes with ethyl diazoacetate.
- Theberge, Cory R.,Verbicky, Christopher A.,Zercher, Charles K.
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p. 8792 - 8798
(2007/10/03)
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- Asymmetric Cyclopropanation Using New Chiral Auxiliaries Derived from D-Fructose
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Acetals of α,β-unsaturated aldehydes with 3-O-alkylated derivatives of 1,2-O-isopropylidene-β-D-fructopyranose and 1,2-O-isopropylidene-β-D-psicopyranose, which are readily available from D-fructose, were cyclopropanated with Et2Zn and CH2I2 with good diastereoselectivity.The effects of structure of the acetals on enantioselectivity were examined.
- Kang, Jahyo,Lim, Geun Jho,Yoon, Suk Kyoon,Kim, Moohi Yoo
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p. 564 - 577
(2007/10/02)
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