- Total Synthesis of Kadcoccinic Acid A Trimethyl Ester
-
The first total synthesis of the trimethyl ester of kadcoccinic acid A is described. The central structural element of our synthesis is a cyclopentenone motif that allows the assembly of the natural product skeleton. A gold(I)-catalyzed cyclization of an enynyl acetate led to efficient construction of the cyclopentenone scaffold. In this step, optimization studies revealed that the stereochemistry of the enynyl acetate dictates regioisomeric cyclopentenone formation. The synthesis further highlights an efficient copper-mediated conjugate addition, merged with a gold(I)-catalyzed Conia-ene reaction to connect the two fragments, thereby forging the D-ring of the natural product. The synthetic strategy reported herein can provide a general platform to access the skeleton of other members of this family of natural products.
- Gholami, Hadi,Trost, Barry M.,Zell, Daniel,Zhang, Guoting
-
supporting information
p. 12286 - 12293
(2021/08/20)
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- Enantiocomplementary Epoxidation Reactions Catalyzed by an Engineered Cofactor-Independent Non-natural Peroxygenase
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Peroxygenases are heme-dependent enzymes that use peroxide-borne oxygen to catalyze a wide range of oxyfunctionalization reactions. Herein, we report the engineering of an unusual cofactor-independent peroxygenase based on a promiscuous tautomerase that accepts different hydroperoxides (t-BuOOH and H2O2) to accomplish enantiocomplementary epoxidations of various α,β-unsaturated aldehydes (citral and substituted cinnamaldehydes), providing access to both enantiomers of the corresponding α,β-epoxy-aldehydes. High conversions (up to 98 %), high enantioselectivity (up to 98 % ee), and good product yields (50–80 %) were achieved. The reactions likely proceed via a reactive enzyme-bound iminium ion intermediate, allowing tweaking of the enzyme's activity and selectivity by protein engineering. Our results underscore the potential of catalytic promiscuity for the engineering of new cofactor-independent oxidative enzymes.
- Crotti, Michele,Kataja, Kim M.,Poelarends, Gerrit J.,Saravanan, Thangavelu,Xu, Guangcai
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supporting information
p. 10374 - 10378
(2020/04/23)
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- Bridgehead Modifications of Englerin A Reduce TRPC4 Activity and Intravenous Toxicity but not Cell Growth Inhibition
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Modifications at the bridgehead position of englerin A were made to explore the effects of variation at this site on the molecule for biological activity, as judged by the NCI 60 screen, in which englerin A is highly potent and selective for renal cancer cells. Replacement of the isopropyl group by other, larger substituents yielded compounds which displayed excellent selectivity and potency comparable to the natural product. Selected compounds were also evaluated for their effect on the ion channel TRPC4 as well as for intravenous toxicity in mice, and these had lower potency in both assays compared to englerin A.
- Wu, Zhenhua,Suppo, Jean-Simon,Tumova, Sarka,Strope, Jonathan,Bravo, Fernando,Moy, Melody,Weinstein, Ethan S.,Peer, Cody J.,Figg, William D.,Chain, William J.,Echavarren, Antonio M.,Beech, David J.,Beutler, John A.
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supporting information
p. 1711 - 1716
(2020/10/19)
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- Enantioselective Total Synthesis of Cotylenin A
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A convergent enantioselective total synthesis of cotylenin A is described. The A-ring fragment, prepared via the catalytic asymmetric intramolecular cyclopropanation developed in our laboratory, and the C-ring fragment, prepared from a known chiral compound via a modified acyl radical cyclization, were successfully assembled by the Utimoto coupling reaction. The formidable carbocyclic eight-membered ring of cotylenin A was efficiently constructed by a palladium-mediated cyclization. All the hydroxy groups in the scaffold were stereoselectively introduced, and a modified reducing reagent, Me4NBH(O2CiPr)3, has been developed. The sugar moiety fragment was prepared via three consecutive carbon-oxygen bond-forming reactions, and the glycosylation was accomplished using Wan's protocol.
- Nagatani, Kotaro,Nakada, Masahisa,Osada, Ryunosuke,Sugiyama, Ryoji,Uwamori, Masahiro
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supporting information
p. 5556 - 5561
(2020/04/10)
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- Total Syntheses and Determination of Absolute Configurations of Cep-212 and Cep-210, Predicted Biosynthetic Intermediates of Tetrodotoxin Isolated from Toxic Newt
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Total syntheses of Cep-212 and Cep-210, predicted biosynthetic intermediates of tetrodotoxin isolated from the Japanese toxic newt, have been accomplished from geraniol by an intramolecular hetero Diels-Alder reaction as a key step in a highly stereoselective manner. The success of these syntheses enabled us to determine their absolute configurations by using a chiral normal-phase HPLC/MS analysis of the bis-dinitrobenzene derivative of natural Cep-212 and reference derivatives prepared from chemically synthesized enantiomers.
- Adachi, Masaatsu,Miyasaka, Tadachika,Kudo, Yuta,Sugimoto, Keita,Yotsu-Yamashita, Mari,Nishikawa, Toshio
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supporting information
p. 780 - 784
(2019/01/21)
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- ENGLERIN DERIVATIVES FOR TREATMENT OF CANCER
-
Disclosed is a compound of formula (I) in which a, R1- R5 and X1 are as described herein. Also disclosed are a pharmaceutical composition containing the compound and a method of using the compound for treating cancer, such as renal cancer.
- -
-
Paragraph 0095-0097
(2019/01/21)
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- Stereochemical Determination of Tuscolid/Tuscorons and Total Synthesis of Tuscoron D and E: Insights into the Tuscolid/Tuscoron Rearrangement
-
The stereochemistry of the structurally unique myxobacterial polyketides tuscolid/tuscorons was determined by a combination of high-field NMR studies, molecular modeling, and chemical derivatization and confirmed by a modular total synthesis of tuscorons D and E. Together with the discovery of three novel tuscorons, this study provides detailed insight into the chemically unprecedented tuscolid/tuscoron rearrangement cascade.
- G?ricke, Bj?rn,Bieber, Michelle Fernandez,Mohr, Kathrin E.,Menche, Dirk
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supporting information
p. 13019 - 13023
(2019/08/30)
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- Borinic Acid/Halide Co-catalyzed Semipinacol Rearrangements of 2,3-Epoxy Alcohols
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A new mode of catalysis of the semipinacol rearrangement of 2,3-epoxy alcohols is described. In combination with a halide salt additive, diarylborinic acids promote a Type II rearrangement that occurs with net retention of configuration. This unusual stereochemical outcome is consistent with a mechanism involving regioselective ring opening of the epoxy alcohol by halide, followed by rearrangement of the resulting halohydrin-derived borinic ester. The protocol is applicable to a range of substrates, enabling ring contractions and expansions as well as stereospecific syntheses of acyclic β-hydroxycarbonyl compounds.
- Tanveer, Kashif,Kim, Seung-Joon,Taylor, Mark S.
-
supporting information
p. 5327 - 5331
(2018/09/13)
-
- Total synthesis of lycopene-5,6-diol and γ-carotene-5′,6′-diol stereoisomers and their HPLC separation
-
Lycopene-5,6-diol stereoisomers (1a,b) and (2a,b) and γ-carotene-5′,6′-diol stereoisomers (3a,b) and (4a,b) were synthesized by a stepwise C15?+?C10?+?C15 double Wittig reaction strategy. The key compounds erythro(anti)-C15-dihydroxy aldehydes 17a,b and their threo(syn)-stereoisomers 23a,b were prepared via Sharpless asymmetric epoxidation of geraniol and nerol followed by acidic hydrolysis of the epoxides in a stereospecific manner. The enantiomerically enriched anti-isomers were obtained by way of recrystallization of 2,3-epoxygeranyl 3,5-dinitrobenzoates 9a,b, whereas syn-isomers were obtained as enantiomerically pure forms via recrystallization of dihydroxyneryl 3,5-dinitrobenzoates 21a,b. In order to determine the absolute stereochemistry of natural products, HPLC separation methods for each enantiomers 1a,b–4a,b were established by using a column carrying a chiral stationary phase.
- Yamano, Yumiko,Nishiyama, Yuya,Aoki, Atsushi,Maoka, Takashi,Wada, Akimori
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p. 2043 - 2052
(2017/03/17)
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- Asymmetric Synthesis of the Antiviral Diterpene Wickerol A
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Wickerol A (1) is an unusual diterpene with remarkable activity against the H1N1 influenza virus. Its tetracyclic skeleton contains three quaternary carbons and is marked by several syn-pentane interactions which force a six-membered ring into a twist-boat conformation. We present an asymmetric synthesis of wickerol A (1) that is based on a Jung Diels-Alder reaction, an intramolecular alkylation to complete the 6-5-6-6 ring system, and a conjugate addition, all of which overcome considerable steric strain. During the synthesis, we isolated an unexpected cyclopropane that presumably stems from a carbonium ion intermediate.
- Liu, Shu-An,Trauner, Dirk
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supporting information
p. 9491 - 9494
(2017/07/24)
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- α,β-Unsaturated Gold(I) Carbenes by Tandem Cyclization and 1,5-Alkoxy Migration of 1,6-Enynes: Mechanisms and Applications
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1,6-Enynes bearing OR groups at the propargyl position generate α,β-unsaturated gold(I)-carbenes/ gold(I) stabilized allyl cations that can be trapped by alkenes to form cyclopropanes or 1,3-diketones to give products of α-alkylation. The best migrating group is p-nitrophenyl ether, which leads to the corresponding products without racemization. Thus, an improved formal synthesis of (+)-schisanwilsonene A has been accomplished. The different competitive reaction pathways have been delineated computationally.
- Calleja, Pilar,Pablo, óscar,Ranieri, Beatrice,Gaydou, Morgane,Pitaval, Anthony,Moreno, María,Raducan, Mihai,Echavarren, Antonio M.
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supporting information
p. 13613 - 13618
(2016/09/13)
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- Synthesis and Biological Evaluation of New (-)-Englerin Analogues
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We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).
- López-Suárez, Laura,Riesgo, Lorena,Bravo, Fernando,Ransom, Tanya T.,Beutler, John A.,Echavarren, Antonio M.
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supporting information
p. 1003 - 1007
(2016/05/24)
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- Asymmetric epoxidation of allylic alcohols catalyzed by vanadium-binaphthylbishydroxamic acid complex
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A vanadium-binaphthylbishydroxamic acid (BBHA) complex-catalyzed asymmetric epoxidation of allylic alcohols is described. The optically active binaphthyl-based ligands BBHA 2a and 2b were synthesized from (S)-1,1'-binaphthyl-2,2'dicarboxylic acid and N-substituted-O-trimethylsilyl (TMS)-protected hydroxylamines via a one-pot, three-step procedure. The epoxidations of 2,3,3-trisubstituted allylic alcohols using the vanadium complex of 2a were easily performed in toluene with a TBHP water solution to afford (2R)-epoxy alcohols in good to excellent enantioselectivities.
- Noji, Masahiro,Kobayashi, Toshihiro,Uechi, Yuria,Kikuchi, Asami,Kondo, Hisako,Sugiyama, Shigeo,Ishii, Keitaro
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supporting information
p. 3203 - 3210
(2015/03/30)
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- Oxidative cyclization of tertiary pentenol derivatives forming 2,5,5-trisubstituted THF rings and the total synthesis of cyclocapitelline
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The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)2 catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline.
- Phillips, Geoffrey A.,Palmer, Cory,Stevens, Andrew C.,Piotrowski, Mathew L.,Dekruyf, Daryl S.R.,Pagenkopf, Brian L.
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supporting information
p. 6052 - 6055
(2015/10/28)
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- Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX
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Allylic alcohols are valuable precursors in the synthesis of pharmaceutical intermediates, agrochemicals and natural products. Regioselective oxidation of parental alkenes is a challenging task for chemical catalysts and requires several steps including protection and deprotection. Many cytochrome P450 enzymes are known to catalyse selective allylic hydroxylation under mild conditions. Here, we describe CYP154E1 from Thermobifida fusca YX that enables this type of oxidation. Several acyclic terpenoids were tested as possible substrates for CYP154E1, and the regio- and chemoselectivity of their oxidation was investigated. Using a previously established bioinformatics approach we identified position 286 in the active site of CYP154E1 which is putatively involved in substrate binding and thereby might have an effect on enzyme selectivity. To tune regio- and chemoselectivity of the enzyme three mutants at position 286 were constructed and used for substrate oxidation. All formed products were analysed with GC-MS and identified using chemically synthesised authentic samples and known compounds as references. Best regioselectivity towards geraniol and nerol was observed with the wild type enzyme mainly leading to 8-hydroxy derivatives (8-hydroxygeraniol or 8-hydroxynerol) with high selectivity (100% and 96% respectively). Highest selectivities during the oxidation of geranylacetone and nerylacetone were observed with the following variants: V286F led mainly to 7-hydroxygeranylacetone (60% of the total product) and V286A produced predominantly 12-hydroxynerylacetone (75% of total product). Thus, CYP154E1 and its mutants expand the tool-box for allylic hydroxylation in synthetic chemistry.
- Bogazkaya, Anna M.,Von Buehler, Clemens J.,Kriening, Sebastian,Busch, Alexandrine,Seifert, Alexander,Pleiss, Juergen,Laschat, Sabine,Urlacher, Vlada B.
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supporting information
p. 1347 - 1353
(2014/07/22)
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- Geranyl and neryl triazole bisphosphonates as inhibitors of geranylgeranyl diphosphate synthase
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When inhibitors of enzymes that utilize isoprenoid pyrophosphates are based on the natural substrates, a significant challenge can be to achieve selective inhibition of a specific enzyme. One element in the design process is the stereochemistry of the isoprenoid olefins. We recently reported preparation of a series of isoprenoid triazoles as potential inhibitors of geranylgeranyl transferase II but these compounds were obtained as a mixture of olefin isomers. We now have accomplished the stereoselective synthesis of these triazoles through the use of epoxy azides for the cycloaddition reaction followed by regeneration of the desired olefin. Both geranyl and neryl derivatives have been prepared as single olefin isomers through parallel reaction sequences. The products were assayed against multiple enzymes as well as in cell culture studies and surprisingly a Z-olefin isomer was found to be a potent and selective inhibitor of geranylgeranyl diphosphate synthase.
- Zhou, Xiang,Ferree, Sarah D.,Wills, Veronica S.,Born, Ella J.,Tong, Huaxiang,Wiemer, David F.,Holstein, Sarah A.
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p. 2791 - 2798
(2014/05/06)
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- Total synthesis of heronapyrrole C
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A flexible total synthesis of the 2-nitropyrrole-derived marine natural product, (+)-heronapyrrole C, is reported. The approach is based on regioselective access to key building blocks containing the rare 4-substituted 2-nitropyrrole motif. Sharpless asymmetric epoxidation and dihydroxylation and a Shi epoxidation were used to introduce the five stereogenic centers of the bis-THF-diol side chain. The N-benzoyloxymethyl (Boz) protecting group was crucial for functionalization of the 2-nitropyrrole moiety and enabling final deprotection under mild conditions.
- Ding, Xiao-Bo,Furkert, Daniel P.,Capon, Robert J.,Brimble, Margaret A.
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supporting information
p. 378 - 381
(2014/04/03)
-
- Catalytic asymmetric synthesis of the Colorado potato beetle pheromone and its enantiomer
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An efficient catalytic asymmetric synthesis of the CPB pheromone [(S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one] and its enantiomer was accomplished with 99% ee and in gram quantities from geraniol. The key steps in this procedure involve Sharpless asymmetric epoxidation and recrystallization of the 4-bromobenzoate from the CPB pheromone to improve its enantiomeric purity. Furthermore, the absolute configuration of the CPB pheromone enantiomer was confirmed as (R) for the first time by the X-ray crystallographic structure of its benzoate.
- Li, Shuo-Ning,Fang, Ling-Lan,Zhong, Jiang-Chun,Shen, Jun-Jian,Xu, Hao,Yang, Yan-Qing,Hou, Shi-Cong,Bian, Qing-Hua
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p. 591 - 595
(2014/05/20)
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- Total syntheses of the squalene-derived halogenated polyethers ent-dioxepandehydrothyrsiferol and armatol A via bromonium- and Lewis acid-initiated epoxide-opening cascades
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Herein we describe in full our investigations leading to the first total syntheses of ent-dioxepandehydrothyrsiferol and armatol A. Discovery of a bromonium-initiated epoxide-opening cascade enabled novel tactics for constructing key fragments found in both natural products and have led us to revise the proposed biogeneses. Other common features found in the routes include convergent fragment coupling strategies to assemble the natural products' backbones and the use of epoxide-opening cascades for rapid constructions of the fused polyether subunits. Through de novo synthesis of armatol A, we elucidate the absolute and relative configuration of this natural product.
- Underwood, Brian S.,Tanuwidjaja, Jessica,Ng, Sze-Sze,Jamison, Timothy F.
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supporting information
p. 5205 - 5220
(2013/07/11)
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- A protecting group-free synthesis of the Colorado potato beetle pheromone
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A novel synthesis of the aggregation pheromone of the Colorado potato beetle, Leptinotarsa decemlineata, has been developed based on a Sharpless asymmetric epoxidation in combination with a chemoselective alcohol oxidation using catalytic [(neocuproine)PdOAc]2OTf2. Employing this approach, the pheromone was synthesized in 3 steps, 80% yield and 86% ee from geraniol.
- Wu, Zhongtao,Jaeger, Manuel,Buter, Jeffrey,Minnaard, Adriaan J.
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supporting information
p. 2374 - 2377
(2014/01/06)
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- TIPSOTf-promoted tandem reaction through rearrangement of epoxides into aldehydes with selective alkyl migration followed by prins-type cyclization to cyclopentanes
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The tandem reaction of trisubstituted epoxides to cyclopentanes promoted by TIPSOTf in nitromethane has been found. It consists of stereospecific rearrangement of epoxides into aldehydes accompanied with selective alkyl migration and subsequent Prins-type cyclization of the aldehydes generated to cyclopentanes. Georg Thieme Verlag Stuttgart · New York.
- Kodama, Takeshi,Harada, Shingo,Tanaka, Takeshi,Tachi, Yoshimitsu,Morimoto, Yoshiki
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body text
p. 458 - 462
(2012/03/27)
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- Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation
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Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis has provided the only precedents. Although non-enzymatic catalysts that meet some of these challenges became known, a comprehensive solution has remained elusive. Here, we describe low molecular weight peptide-based catalysts, discovered through a combinatorial synthesis and screening protocol, that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features reminiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for the asymmetric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternative-site selectivity in comparison to oxidation catalysts previously described.
- Lichtor, Phillip A.,Miller, Scott J.
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p. 990 - 995
(2013/02/25)
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- Epoxidation studies of terpenes with urea hydrogen peroxide and phosphotungstic acid
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Epoxidation of isolated and allylic olefins with dodecaphosphotungstic acid, H3[PW12O40]xH2O and urea hydrogen peroxide (UHP) adduct as an oxidant has successfully been carried out under homogenous conditions with the aid of isopropanokwater (4:1) as solvent, thereby avoiding the use of expensive phase transfer catalyst. The method has proven to be efficient in terms of percent yield, cost, reaction conditions and ease of work-up.
- Kaur, Damandeep,Manktala,Chahal,Chhabra
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experimental part
p. 598 - 602
(2011/01/04)
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- Oxidation catalysis of Nb(salan) complexes: Asymmetric epoxidation of allylic alcohols using aqueous hydrogen peroxide as an oxidant
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Several optically active Nb(salan) complexes were synthesized, and their oxidation catalysis was examined. A dimeric μ-oxo Nb(salan) complex that was prepared from Nb(OiPr)5 and a salan ligand was found to catalyze the asymmetric epoxidation of allylic alcohols using a urea-hydrogen peroxide adduct as an oxidant with good enantioselectivity. However, subsequent studies of the time course of this epoxidation and of the relationship between the ee of the ligand and the ee of the product indicated that the μ-oxo dimer dissociates into a monomeric species prior to epoxidation. Moreover, monomeric Nb(salan) complexes prepared in situ from Nb(OiPr)5 and salan ligands followed by water treatment were found to catalyze the epoxidation of allylic alcohols better using aqueous hydrogen peroxide in CHCl3/brine or toluene/brine solution with high enantioselectivity ranging from 83 to 95% ee, except for the reaction of cinnamyl alcohol that showed a moderate ee of 74%. This is the first example of the highly enantioselective epoxidation of allylic alcohols using aqueous hydrogen peroxide as an oxidant.
- Egami, Hiromichi,Oguma, Takuya,Katsuki, Tsutomu
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scheme or table
p. 5886 - 5895
(2010/07/05)
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- Vanadium-catalyzed asymmetric epoxidation of allylic alcohols in water
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Asymmetric V-catalyzed epoxidation of allylic alcohols can be carried out in water with chiral ligands, which incorporate sulfonamide and hydroxamic acid fragments. Furthermore, the reaction, notorious for its ligand-deceleration effect, in water turned into the ligand-accelerated process. By using this aqueous protocol, a range of allylic alcohols were epoxidized with up to 94% ee.
- Malkov, Andrei V.,Czemerys, Louise,Malyshev, Denis A.
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supporting information; experimental part
p. 3350 - 3355
(2009/09/26)
-
- An optimised and recoverable tartrate surrogate for sharpless asymmetric epoxidations
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The tetrahydroxy diester 7d (R = iPr) is almost as effective as diisopropyl tartrate in SAE reactions of (E)-allylic alcohols and can be recovered and re-used following a relatively simple work-up procedure.
- Knight, David W.,Morgan, Ian R.
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scheme or table
p. 35 - 38
(2009/05/07)
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- Synthesis of N-heterocycles, beta-amino acids, and allyl amines via aza-payne mediated reaction of ylides and hydroxy aziridines
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An ylide-based aza-Payne rearrangement of 2,3-aziridin-1-ols leads to an efficient process for the preparation of pyrrolidines. The aza-Payne rearrangement under the basic reaction conditions favors the formation of epoxy amines. Subsequent nucleophilic attack of the epoxide by the ylide yields a bis-anion, which upon a 5-exo-tet ring closure yields the desired pyrrolidine, thus completing the relay of the 3-membered the 5-membered nitrogen containing ring system. This process takes place with complete transfer of stereochemical fidelity, and can be applied to sterically hindered aziridinols.
- -
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Page/Page column 46
(2009/01/23)
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- Direct immobilization of self-assembled polyoxometalate catalyst in layered double hydroxide for heterogeneous epoxidation of olefins
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We present a novel method for the fabrication of immobilized polyoxometalate catalysts that directly use a self-assembled polyoxometalate solution without isolation and purification. Specifically, self-assembled [WZn3(ZnW9O34)2]12- catalyst can be selectively immobilized into layered double hydroxides in the presence of undesired anions. The material thus obtained demonstrates high dispersion and good hydrothermal stability. The heterogenized catalyst exhibits excellent activity (turnover frequency up to 18,000 h-1 at 50 °C) in the epoxidation of allylic alcohols with aqueous H2O2 and can be readily recycled with no apparent loss of performance.
- Liu, Peng,Wang, Hong,Feng, Zhaochi,Ying, Pinliang,Li, Can
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p. 345 - 348
(2008/09/21)
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- Stereoselective total synthesis of natural (S)-bakuchiol and its enantiomer
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A practical stereoselective synthesis of (S)-bakuchiol (1) and its enantiomer is reported. The important intermediate, (R)-configured β-siloxy aldehyde 5, was obtained in three steps from the easily available material geraniol (2) via the key step of Yamamoto's rearrangement of epoxy silyl ethers. (S)-Bakuchiol (1) and its enantiomer, (R)-bakuchiol (17), were finally obtained in different synthetic sequences with overall yields of 51% (ten steps) and 40% (nine steps) from geraniol (2), respectively.
- Du, Xiao-Long,Chen, Hong-Li,Feng, Hui-Jin,Li, Yuan-Chao
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experimental part
p. 371 - 378
(2009/02/07)
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- Prompt determination of absolute configuration for epoxy alcohols via exciton chirality protocol
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A microscale protocol for determination of absolute configurations of 2,3-epoxy alcohols is described. 2,3-Disubstituted (cis and trans), 2,2-disubstituted, 2,2,3-trisubstituted, and 2,3,3-trisubstituted epoxy alcohols rendered prominent ECCD signals upon complexing with a Lewis acidic porphyrin tweezer and consequently provide straightforward assignment of chirality for epoxy alcohols. This method proved to be rapid, simple, sensitive, and reliable for the class of molecules listed above. Copyright
- Li, Xiaoyong,Borhan, Babak
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supporting information; experimental part
p. 16126 - 16127
(2009/05/09)
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- A short enantioselective synthesis of N-boc-(2R,3R)-3-methyl-3- hydroxypipecolic acid from geraniol
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(Chemical Equation Presented) The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.
- Noe, Mark C.,Hawkins, Joel M.,Snow, Sheri L.,Wolf-Gouveia, Lilli
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p. 3295 - 3298
(2008/09/19)
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- Nb(salan)-catalyzed asymmetric epoxidation of allylic alcohols with hydrogen peroxide
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(Chemical Presented) Bridging the catalyst: The dimeric complex [(m-oxo){Nb(salan)}2] catalyzes asymmetric epoxidation of allylic alcohols by hydrogen peroxide to give epoxy alcohols with good to high enantioselectivities irrespective of the olefin geometry (see scheme).
- Egami, Hiromichi,Katsuki, Tsutomu
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experimental part
p. 5171 - 5174
(2009/04/04)
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- Development and application of versatile bis-hydroxamic acids for catalytic asymmetric oxidation
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In this article, we describe the development and preliminary results of our new designed C2-symmetric bis-hydroxamic acid (BHA) ligands and the application of the new ligands for vanadium-catalyzed asymmetric epoxidation of allylic alcohols as well as homoallylic alcohols. From this success we demonstrate the versatile nature of BHA in the molybdenum catalyzed asymmetric oxidation of unfunctionalized olefins and sulfides.
- Barlan, Allan U.,Zhang, Wei,Yamamoto, Hisashi
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p. 6075 - 6087
(2008/02/03)
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- A short and efficient synthetic strategy for the total syntheses of (S)-(+)- and (R)-(-)-Plakolide A
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Concise and efficient total syntheses of anticancer agents (S)-(+)-Plakolide A and (R)-(-)-Plakolide A were accomplished in eight steps and an overall yield of 39 % starting from geraniol. The key steps in our strategy are Sharpless asymmetric epoxidation, double elimination, and Stille coupling reactions. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Mohapatra, Debendra K.,Pramanik, Chinmoy,Chorghade, Mukund S.,Gurjar, Mukund K.
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p. 5059 - 5063
(2008/03/18)
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- Identification of carbon-centred radicals derived from linalyl hydroperoxide, a strong skin sensitizer: A possible route for protein modifications
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Few studies are reported on the formation of reactive carbon-centred radical species from toxic xenobiotics. In this paper the formation of carbon radicals derived from the skin sensitizer linalyl hydroperoxide is described using radical trapping and EPR studies. Radical trapping used TMIO as scavenger agent and light, heat or TPP-Fe3+ as radical inducers. EPR spin trapping was based on the use of the parent alcohol, generating the same allyloxyl radical than the hydroperoxide by photolysis of the corresponding nitrite formed with t-BuONO, also playing the role of the spin trap. It is suggested that the generation of these carbon radical species could play an important role for the binding of the hydroperoxide with skin proteins to form antigenic structures, the first step of the skin sensitization mechanism.
- Bezard, Michael,Gimenez-Arnau, Elena,Meurer, Bernard,Grossi, Loris,Lepoittevin, Jean-Pierre
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p. 3977 - 3986
(2007/10/03)
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- Enzyme-assisted synthesis of (S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one, the male-produced aggregation pheromone of the Colorado potato beetle, and its (R)-enantiomer
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(S)-1,3-Dihydroxy-3,7-dimethyl-6-octen-2-one, the male-produced aggregation pheromone of the Colorado potato beetle (Leptinotarsa decemlineata), and its (R)-isomer were synthesized by employing lipase-catalyzed asymmetric acetylation of (±)-2,3-epoxynerol as the key step.
- Tashiro, Takuya,Mori, Kenji
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p. 1801 - 1806
(2007/10/03)
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- Catalytic asymmetric epoxidation
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The present invention relates to the synthesis of chiral epoxides via a catalytic asymmetric oxidation of olefins. Additionally, the methodology provides a method of asymmetrically oxidizing sulfides and phosphines. This asymmetric oxidation employs a catalyst system composed of a metal and a chiral bishydroxamic acid ligand, which, in the presence of a stoichiometric oxidation reagent, serves to asymmetrically oxidize a variety of substrates.
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Page/Page column 14-15
(2010/02/12)
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- Enantioselective total synthesis of (-)-curcuquinone via regioselective chromium-mediated benzannulation
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(Chemical Equation Presented) A short and efficient, high-yielding enantioselective total synthesis of the marine natural product (-)-curcuquinone 1 is reported involving a regioselective [3 + 2 + 1]-benzannulation reaction as the key step. Additionally, this strategy allows the isolation of curcuhydroquinone monomethyl ether 9 as an intermediate of the benzannulation reaction and its subsequent further protection toward diversified hydroquinones.
- Minatti, Ana,Doetz, Karl Heinz
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p. 3745 - 3748
(2007/10/03)
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- Enantioselective syntheses of trans-3,4-difluoropyrrolidines and investigation of their applications in catalytic asymmetric synthesis
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Asymmetric syntheses of enantiopure trans-3,4-difluoropyrrolidines have been prepared by the introduction of fluorine at both centers in a single operation; asymmetric epoxidations and additions to benzaldehyde were conducted using catalysts whose chirality depends on organofluorine asymmetry.
- Marson, Charles M.,Melling, Robert C.
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p. 9771 - 9779
(2007/10/03)
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- Enantioselective epoxidation of allylic alcohols by a chiral complex of vanadium: An effective controller system and a rational mechanistic model
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(Chemical Equation Presented) Bishydroxamic acid derivatives are used as ligands for a vanadium catalyst in the preparation of epoxy alcohols (see scheme). The methodology uses aqueous tert-butyl hydroperoxide (TBHP) as an achiral oxidant, low catalyst loading, low reaction temperatures (0°C to room temperature), and simple workup procedures. The reaction is applied to the kinetic resolution of a secondary allylic alcohol and the preparation of small epoxy alcohols. R1, R2, R3: alkyl, aryl, H.
- Zhang, Wei,Basak, Arindrajit,Kosugi, Yuji,Hoshino, Yujiro,Yamamoto, Hisashi
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p. 4389 - 4391
(2007/10/03)
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- Amino acid-derived hydroxamic acids as chiral ligands in the vanadium catalysed epoxidation
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New sulfonamide-derived hydroxamic acids 7-11 have been developed as chiral ligands for the V-catalysed asymmetric epoxidation, showing high reactivity at subzero temperatures and moderate to good enantioselectivity. The strong accelerating effect exhibited by the ligands of this type can be attributed to the sulfonamide functionality. A range of cinnamyl type allylic alcohols were epoxidised with up to 74% ee. The Royal Society of Chemistry 2005.
- Malkov, Andrei V.,Bourhani, Zainaba,Kocovsky, Pavel
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p. 3194 - 3200
(2007/10/03)
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- From C-glycosides to pyranopyrans: An approach to thyrsiferol using titanium(III)-promoted redox couplings
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An approach to the pyranopyran ring system that is found in many natural products, including thyrsiferol, is described. The route entails the assembly of an α,β-unsaturated ketone (11) from geraniol and dihydropyran (23) from acetyl acetaldehyde dimethyl acetal (19) and their titanium-(III)-promoted coupling to afford a respectable 60% yield of keto alcohol 26. The σ-bond formed in this process corresponds to the pro-C9-C10 bond of thyrsiferol (4). Attempts to invert the stereochemistry at the pro-C 11 center were thwarted by the congestion imparted by the presence of the vicinal TBS-ether. Consequently, cyclization of the coupling adduct under conditions developed by Olah and Prakash and co-workers led to the cis-fused pyranopyran 27. X-ray analysis of this crystalline material confirmed each of the stereochemical assignments. After much effort, it was determined that the hydroxyl group at C12 could be removed by treating the derived methyl xanthate with a tri-n-butylphosphine-borane complex under radical-forming conditions. The reaction sequence worked well, despite the hindered working environment and the presence of a potentially labile C-Br bond.
- Nishiguchi, Gisele A.,Little, R. Daniel
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p. 5249 - 5256
(2007/10/03)
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- Ligand-accelerated vanadium-catalysed epoxidation in water
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Vanadium-catalysed epoxidation of allylic alcohols, a classical example of ligand-decelerated catalysis, in water it turns into a ligand-accelerated process. The Royal Society of Chemistry 2005.
- Bourhani, Zainaba,Malkov, Andrei V.
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p. 4592 - 4594
(2007/10/03)
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- Organocatalytic asymmetric epoxidation reactions in water-alcohol solutions
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The diastereo- and enantioselective organocatalytic epoxidation of α,β-unsaturated aldehydes in aqueous solutions is presented. By the screening of the reaction conditions for the epoxidation of cinnamic aldehyde applying hydrogen peroxide as the oxidant and 2-[bis-(3,5-bis-trifluoromethyl- phenyl)-trimethylsilanyloxy-methyl]-pyrrolidine as the catalyst, a highly stereoselective reaction has been developed. The scope of the diastereo- and enantioselective organocatalytic epoxidation in aqueous solutions is documented by the asymmetric epoxidation of α,β-unsaturated aldehydes with enantioselectivities up to 96% ee. The Royal Society of Chemistry 2005.
- Zhuang, Wei,Marigo, Mauro,Jorgensen, Karl Anker
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p. 3883 - 3885
(2007/10/03)
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- Synthesis of diastereomerically and enantiomerically pure 2,3-disubstituted tetrahydrofurans using a sulfoxonium ylide
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Nucleophilic substitution reactions of 2,3-epoxy alcohols, easily prepared via Sharpless asymmetric epoxidation chemistry, offer access to a wide variety of enantiomerically pure compounds. In this communication, we describe the use of a Payne rearrangement to control regioselectivity in the ring-opening of a series of 2,3-epoxy alcohols with dimethylsulfoxonium methylide to yield diastereomerically and/or enantiomerically pure disubstituted tetrahydrofuran rings. The factors influencing the success and substitution pattern of the THF ring products are discussed, including steric, electronic, and solvent effects. Copyright
- Schomaker, Jennifer M.,Pulgam, Veera Reddy,Borhan, Babak
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p. 13600 - 13601
(2007/10/03)
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- Alkene substituents for selective activation of endo-regioselective polyepoxide oxacyclizations
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(Chemical equation presented) The presence of an alkenyl substituent on the terminal epoxide of a polyepoxide substrate enhances the yield of all-endo-regioselective tandem oxacyclization to trans-syn-trans-fused polycyclic ethers. For a substrate in which the epoxide and alkene functional groups are separated by two methylene substituents, a novel bromonium ion-induced endo-regioselective cyclization to bromooxepane is also described.
- Bravo, Fernando,McDonald, Frank E.,Neiwert, Wade A.,Hardcastle, Kenneth I.
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p. 4487 - 4489
(2007/10/03)
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- Selective epoxidation of monoterpenes with H2O2 and polymer-supported methylrheniumtrioxide systems
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A convenient and efficient synthesis of monoterpene epoxides by application of heterogeneous poly(4-vinylpyridine)/methyl rhenium trioxide (PVP/MTO) and polystyrene/methyl rhenium trioxide (PS/MTO) systems is described. Even highly sensitive terpenic epoxides were obtained in excellent yield. Environment friendly, easily available, and low cost H2O2 was used as oxidant. Catalysts were stable systems for at least five recycling experiments.
- Saladino, Raffaele,Neri, Veronica,Pelliccia, Anna Rita,Mincione, Enrico
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p. 7403 - 7408
(2007/10/03)
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- Regio- and stereoselectivity of diethylaluminum azide opening of trisubstituted epoxides and conversion of the 3° azidohydrin adducts to isoprenoid aziridines
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The regioisomer ratios (3°,2°/2°,3°), and in some cases the stereochemistry, of vicinal azidohydrins formed in reactions of 11 trisubstituted terpene epoxides with Et2AlN3 in toluene are reported. The more highly substituted azide usually predominated (3°,2°/2°,3° ratios ≥ 40:1 to 2.5-1) in accord with a Markovnikov orientation and an SN1-like transition state. Reversed regioisomer ratios were observed with 6,7-epoxygeranyl acetate (1:2.5) and cis-1,2-epoxylimonene (1:3.3 to 1:10). The tertiary azido diols from 2,3-epoxygeraniol, 2,3-epoxyfarnesol, and 2,3-epoxynerol were formed as single isomers with inversion of configuration at C3 (≥ 35-40:1 for the C10 azido diols). The regioselectivity was affected by the presence and proximity of oxy functional groups on the epoxide substrate (OH, OAc, and OSi-tBuMe2), the equivalents of Et2AlN3, and additives (EtOAc or EtOH). The results and trends are rationalized by consideration of the structural and stereoelectronic characteristics of proposed diethylaluminum epoxonium ion intermediates and transition states, together with the nucleophilicity of the azide donor. Six of the 3°,2° azidohydrins were converted to the corresponding aziridines by primary-selective silylations of four azido diols, mesylations, and reductive cyclizations with LiAlH4.
- Davis, Chad E.,Bailey, Jessica L.,Lockner, Jonathan W.,Coates, Robert M.
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- Highly efficient catalytic asymmetric epoxidation of allylic alcohols by an oxovanadium-substituted polyoxometalate with a regenerative TADDOL-derived hydroperoxide
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(Matrix presented) The oxovanadium(IV) sandwich-type POM catalyzes the chemo-, regio-, and stereoselective epoxidation of allylic alcohols by chiral hydroperoxides with very high catalytic efficiency (up to 42 000 TON), a potentially valuable oxidation for the development of sustainable processes. By using the sterically demanding, TADDOL-derived hydroperoxide TADOOH as the chiral oxygen source, enantiomeric ratios (er) of up to 95:5 have been achieved.
- Adam, Waldemar,Alsters, Paul L.,Neumann, Ronny,Saha-Moeller, Chantu R.,Seebach, Dieter,Zhang, Rui
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p. 725 - 728
(2007/10/03)
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- Endo-oxacyclizations of polyepoxides: Biomimetic synthesis of fused polycyclic ethers
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Boron trifluoride-etherate promotes the endo-selective oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The mechanism of the oxacyclization reaction probably involves intramolecular nucleophilic addition of epoxide oxygen to open another epoxide that is activated as an electrophile by the Lewis acid. These oxacyclizations proceed stereospecifically with inversion of configuration upon opening of each epoxide to provide trans-fused polycyclic products. The oxacyclization cascade is terminated by a tethered nucleophile, which may be the carbonyl oxygen of a ketone, ester, or carbonate, or a trisubstituted alkene. The best oxacyclization yields are generally observed with tert-butyl carbonate as the terminating nucleophile, although in some cases the oxacyclization products include formation of tert-butyl ethers as a minor product. The oxacyclization transformations described herein may mimic ring-forming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products.
- McDonald, Frank E.,Bravo, Fernando,Wang, Xia,Wei, Xudong,Toganoh, Motoki,Rodriguez, J. Ramon,Do, Bao,Neiwert, Wade A.,Hardcastle, Kenneth I.
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p. 2515 - 2523
(2007/10/03)
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