- Oxidation of Unsaturated Aliphatic and Arylalkyl Alcohols by Peroxydisulphate. Intramolecular Cyclization of Alkoxyl Radicals
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Oxidation of unsaturated aliphatic and arylalkyl alcohols by the sodium peroxydisulphate-silver salt system has benn studied.Both classes of alcohols lead to cyclic ethers through different pathways.The ratio of five- to six-membered cyclic ethers was est
- Clerici, Angelo,Porta, Ombretta
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- Direct C-H bond activation of ethers and successive C-C bond formation with benzene by a bifunctional palladium-titania photocatalyst
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Palladium-loaded titanium oxide was found to work as a bifunctional photocatalyst for functionalization of benzene with ether upon photoirradiation, without using any special reagents. The metal-loaded TiO2 photocatalyst activated a C-H bond of ethers and the heterogeneous Pd metal nanoparticle catalyst promoted the successive C-C bond formation between benzene and the radical species. In this reaction, benzene reacted very selectively with the α-carbon of various ethers at least in the initial stage of the reaction. Kinetic and ESR studies revealed a detailed mechanism for the reaction.
- Tyagi, Akanksha,Matsumoto, Tomoya,Kato, Tatsuhisa,Yoshida, Hisao
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- An unprecedented coupling reaction of arylmagnesium compounds with tetrahydrofuran providing 2-aryltetrahydrofuran mediated by an iodoalkane- EtMgBr system
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An extremely facile coupling reaction between arylmagnesium compounds and THF by means of an iodoalkane-EtMgBr system provides 2- aryltetrahydrofurans. One-pot synthesis of 2thienyltetrahydrofuran is achieved from thiophene and THF using this coupling reaction.
- Inoue, Atsushi,Shinokubo, Hiroshi,Oshima, Koichiro
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- Radical C(sp3)-H Heck-type Reaction of N-Alkoxybenzimidoyl Chlorides with Styrenes to Construct Alkenols
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We report the first radical C(sp3)-H Heck-type reaction of aliphatic alcohols for selective δ- and ?-alkenol synthesis by photoredox catalysis. N-Alkoxybenzimidoyl chlorides are developed as novel alkoxyl radical precursors with tunable redox potentials. Various alkenols can be constructed by the inert C(sp3)-H Heck-type reaction of 4-cyano-N-alkoxybenzimidoyl chlorides with styrene derivatives under redox-neutral conditions, which can be performed on the gram scale and can be easily derivatized.
- Fang, Di,Zhang, Yidan,Chen, Yiyun
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p. 2050 - 2054
(2022/03/17)
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- Bis(trifluoromethanesulfonimide) (BSI): Acidity and application to hydrofunctionalization as a Br?nsted acid catalyst
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A binaphthyl derivative, bearing bis(trifluoromethanesulfonimide) (BSI) moiety, was developed as a novel Br?nsted acid. Computational prediction of the pKa value of BSI indicated its classification as a strong Br?nsted acid. BSI catalyzed the h
- Takagi, Ryukichi,Sakai, Yuichiro,Duong, Duyen Thi
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- C1-Symmetric Binap Derivative Featuring Single Diferrocenylphosphino-Donor Moiety
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A C1-symmetric chiral bisphosphine, FcPh-Binap (1), which possesses a single diferrocenylphosphino moiety together with a conventional Ph2P-substituent, was prepared in enantiomerically pure forms. Ligand 1 is sterically less demanding than Fc-Segphos (A)
- Enomoto, Yuuki,Ichiryu, Hiroki,Hu, Hao,Ura, Yasuyuki,Ogasawara, Masamichi
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p. 1020 - 1024
(2021/05/07)
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- An Intramolecular Iodine-Catalyzed C(sp3)?H Oxidation as a Versatile Tool for the Synthesis of Tetrahydrofurans
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The formation of ubiquitous occurring tetrahydrofuran patterns has been extensively investigated in the 1960s as it was one of the first examples of a non-directed remote C?H activation. These approaches suffer from the use of toxic transition metals in overstoichiometric amounts. An attractive metal-free solution for transforming carbon-hydrogen bonds into carbon-oxygen bonds lies in applying economically and ecologically favorable iodine reagents. The presented method involves an intertwined catalytic cycle of a radical chain reaction and an iodine(I/III) redox couple by selectively activating a remote C(sp3)?H bond under visible-light irradiation. The reaction proceeds under mild reaction conditions, is operationally simple and tolerates many functional groups giving fast and easy access to different substituted tetrahydrofurans.
- Br?se, Stefan,Koch, Vanessa
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p. 3478 - 3483
(2021/07/22)
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- H3PO2-Catalyzed Intramolecular Stereospecific Substitution of the Hydroxyl Group in Enantioenriched Secondary Alcohols by N-, O-, and S-Centered Nucleophiles to Generate Heterocycles
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The direct intramolecular stereospecific substitution of the hydroxyl group in enantiomerically enriched secondary benzylic, allylic, propargylic, and alkyl alcohols was successfully accomplished by phosphinic acid catalysis. The hydroxyl group was displaced by O-, S-, and N-centered nucleophiles to provide enantioenriched five-membered tetrahydrofuran, pyrrolidine, and tetrahydrothiophene as well as six-membered tetrahydroquinolines and chromanes in up to a 99% yield and 100% enantiospecificity with water as the only byproduct. Mechanistic studies using both experiments and calculations have been performed for substrates generating 5-membered heterocycles. Rate studies show dependences in a catalyst, an internal nucleophile, and an electrophile, however, independence in an external nucleophile, an electrophile, or water. Kinetic isotope effect studies show an inverse KIE of kH/kD = 0.79. Furthermore, phosphinic acid does not promote SN1 reactivity. Computational studies support a bifunctional role of the phosphinic acid in which activation of both nucleofuge and nucleophile occurs in a bridging SN2-type transition state. In this transition state, the acidic hydrogen of phosphinic acid protonates the leaving hydroxyl group simultaneously as the oxo group partially deprotonates the nucleophile. Thereby, phosphinic acid promotes the substitution of the nonderivatized hydroxyl group in enantioenriched secondary alcohols by uncharged nucleophiles with conservation of the chirality from the alcohol to the heterocycle.
- Biswas, Srijit,Bunrit, Anon,Dahlstrand, Christian,Huang, Genping,Rukkijakan, Thanya,Samec, Joseph S. M.,Srifa, Pemikar,Watile, Rahul A.
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p. 1344 - 1352
(2020/01/31)
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- Alcohol Etherification via Alkoxy Radicals Generated by Visible-Light Photoredox Catalysis
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A mechanistically divergent method is described that, employing a commercially available hypervalent iodine(III) reagent, generates alkoxy radicals from 1°, 2°, and 3° alcohols and allows their use in the functionalization of C(sp3)-H and C(sp2)-H bonds. This visible-light photoredox catalysis produces alkyl ethers via 1,5/6-hydrogen atom transfer or aryl ethers via 1,5-addition. This mild methodology provides a practical strategy for the synthesis of acetals, orthoesters, tetrahydrofurans, and chromanes.
- Rivero, Alexandra R.,Fodran, Peter,Ondrejková, Alica,Wallentin, Carl-Johan
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p. 8436 - 8440
(2020/11/03)
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- Site- And enantiodifferentiating C(sp3)-H oxidation enables asymmetric access to structurally and stereochemically diverse saturated cyclic ethers
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A manganese-catalyzed site- and enantiodifferentiating oxidation of C(sp3)-H bonds in saturated cyclic ethers has been described. The mild and practical method is applicable to a range of tetrahydrofurans, tetrahydropyrans, and medium-sized cyclic ethers with multiple stereocenters and diverse substituent patterns in high efficiency with extremely efficient site- and enantiodiscrimination. Late-stage application in complex biological active molecules was further demonstrated. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity. The ability to employ ether substrates as the limiting reagent, together with a broad substrate scope, and a high level of chiral recognition, represent a valuable demonstration of the utility of asymmetric C(sp3)-H oxidation in complex molecule synthesis.
- Liu, Lei,Sun, Shutao,Yang, Yiying,Zhang, Dongju,Zhao, Ran
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p. 19346 - 19353
(2020/12/01)
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- Novel method for preparing oxygen heterocyclic compound through ionic liquid catalysis
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The invention discloses a novel method for preparing an oxygen heterocyclic compound through ionic liquid catalysis. The ionic liquid catalytic system has the advantages of high efficiency, simplicity, mild reaction conditions, no metal participation, no by-product, simple separation and the like and can efficiently catalyze fatty diether metathesis cyclization to prepare an oxygen heterocyclic compound and has very high industrial application value.
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Paragraph 0061-0072
(2020/08/02)
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- Aryl Boronic Acid Catalysed Dehydrative Substitution of Benzylic Alcohols for C?O Bond Formation
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A combination of pentafluorophenylboronic acid and oxalic acid catalyses the dehydrative substitution of benzylic alcohols with a second alcohol to form new C?O bonds. This method has been applied to the intermolecular substitution of benzylic alcohols to form symmetrical ethers, intramolecular cyclisations of diols to form aryl-substituted tetrahydrofuran and tetrahydropyran derivatives, and intermolecular crossed-etherification reactions between two different alcohols. Mechanistic control experiments have identified a potential catalytic intermediate formed between the aryl boronic acid and oxalic acid.
- Estopi?á-Durán, Susana,Donnelly, Liam J.,Mclean, Euan B.,Hockin, Bryony M.,Slawin, Alexandra M. Z.,Taylor, James E.
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supporting information
p. 3950 - 3956
(2019/02/16)
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- Nonclassical Mechanism in the Cyclodehydration of Diols Catalyzed by a Bifunctional Iridium Complex
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1,4- and 1,5-diols undergo cyclodehydration upon treatment with cationic N-heterocyclic carbene (NHC)–IrIII complexes to give tetrahydrofurans and tetrahydropyrans, respectively. The mechanism was investigated, and a metal-hydride-driven pathway was proposed for all substrates, except for very electron-rich ones. This contrasts with the well-established classical pathways that involve nucleophilic substitution.
- González Miera, Greco,Bermejo López, Aitor,Martínez-Castro, Elisa,Norrby, Per-Ola,Martín-Matute, Belén
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supporting information
p. 2631 - 2636
(2019/02/01)
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- Dual Photoredox/Copper Catalysis for the Remote C(sp3)?H Functionalization of Alcohols and Alkyl Halides by N-Alkoxypyridinium Salts
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Under mild dual photoredox/copper catalysis, the reaction of N-alkoxypyridinium salts with readily available silyl reagents (TMSN3, TMSCN, TMSNCS) afforded δ-azido, δ-cyano, and δ-thiocyanato alcohols in high yields. The reaction went through a domino process involving alkoxy radical generation, 1,5-hydrogen atom transfer (1,5-HAT) and copper-catalyzed functionalization of the resulting C-centered radical. Conditions for catalytic enantioselective δ-C(sp3)?H cyanation were also documented.
- Bao, Xu,Wang, Qian,Zhu, Jieping
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supporting information
p. 2139 - 2143
(2019/01/25)
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- The Combination of Benzaldehyde and Nickel-Catalyzed Photoredox C(sp3)?H Alkylation/Arylation
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Herein we report a highly selective photoredox C(sp3)?H alkylation/arylation of ethers through the combination of a photo-organocatalyst (benzaldehyde) and a transition-metal catalyst (nickel). This method provides a simple and general strategy for the C(sp3)?H alkylation/arylation of ethers. A selective late-stage modification of (?)-ambroxide has also been conducted to demonstrate the applicability of the method.
- Zhang, Lumin,Si, Xiaojia,Yang, Yangyang,Zimmer, Marc,Witzel, Sina,Sekine, Kohei,Rudolph, Matthias,Hashmi, A. Stephen K.
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supporting information
p. 1823 - 1827
(2019/01/14)
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- Visible-Light-Induced C-O Bond Formation for the Construction of Five- and Six-Membered Cyclic Ethers and Lactones
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Visible-light-induced intramolecular C-O bond formation was developed using 2,4,6-triphenylpyrylium tetrafluoroborate (TPT), which allows the regiocontrolled construction of cyclic ethers and lactones. The reaction is likely to proceed through the single-electron oxidation of the phenyl group, followed by the formation of a benzylic radical, thus preventing a competing 1,5-hydrogen abstraction pathway. Detailed mechanistic studies suggest that molecular oxygen is used to trap the radical intermediate to form benzyl alcohol, which undergoes cyclization. This new approach serves as a powerful platform by providing efficient access to valuable five- and six-membered cyclic ethers and lactones with a unified protocol.
- Im, Honggu,Kang, Dahye,Choi, Soyeon,Shin, Sanghoon,Hong, Sungwoo
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supporting information
p. 7437 - 7441
(2018/11/27)
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- Anodic benzylic C(sp3)-H amination: Unified access to pyrrolidines and piperidines
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An electrochemical aliphatic C-H amination strategy was developed to access the important heterocyclic motifs of pyrrolidines and piperidines within a uniform reaction protocol. The mechanism of this unprecedented C-H amination strategy involves anodic C-H activation to generate a benzylic cation, which is efficiently trapped by a nitrogen nucleophile. The applicability of the process is demonstrated for 40 examples comprising both 5- and 6-membered ring formations.
- Herold, Sebastian,Bafaluy, Daniel,Mu?iz, Kilian
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supporting information
p. 3191 - 3196
(2018/07/29)
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- Enantioselective Radical Cyclization for Construction of 5-Membered Ring Structures by Metalloradical C-H Alkylation
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Radical cyclization represents a powerful strategy for construction of ring structures. Traditional radical cyclization, which is based on radical addition as the key step, necessitates the use of unsaturated substrates. Guided by the concept of metalloradical catalysis, a different mode of radical cyclization that can employ saturated C-H substrates is demonstrated through the development of a Co(II)-based system for catalytic activation of aliphatic diazo compounds for enantioselective radical alkylation of various C(sp3)-H bonds. It allows for efficient construction of chiral pyrrolidines and other valuable 5-membered cyclic compounds. This alternative strategy of radical cyclization provides a new retrosynthetic paradigm to prepare five-membered cyclic molecules from readily available open-chain aldehydes through the union of C-H and C=O elements for C-C bond formation.
- Wang, Yong,Wen, Xin,Cui, Xin,Zhang, X. Peter
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p. 4792 - 4796
(2018/04/17)
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- Practical Intermolecular Hydroarylation of Diverse Alkenes via Reductive Heck Coupling
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The hydroarylation of alkenes is an attractive approach to construct carbon-carbon (C-C) bonds from abundant and structurally diverse starting materials. Herein we report a palladium-catalyzed reductive Heck hydroarylation of aliphatic and heteroatom-substituted terminal alkenes and select internal alkenes with an array of (hetero)aryl iodides. The reaction is anti-Markovnikov selective with terminal alkenes and tolerates a wide variety of functional groups on both the alkene and (hetero)aryl coupling partners. Additionally, applications of this method to complex molecule diversifications are demonstrated. Mechanistic experiments are consistent with a mechanism in which the key alkylpalladium(II) intermediate is intercepted with formate and undergoes a decarboxylation/C-H reductive elimination cascade to afford the saturated product and turn over the cycle.
- Gurak, John A.,Engle, Keary M.
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p. 8987 - 8992
(2018/09/11)
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- Direct cross-coupling between alkenes and tetrahydrofuran with a platinum-loaded titanium oxide photocatalyst
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A Pt-loaded TiO2 photocatalyst successfully catalyzed the direct cross-coupling between various alkenes and tetrahydrofuran (THF) without any additional oxidizing agent. The reaction between cyclohexene and THF gave three cross-coupling products, namely, 2-cyclohexyltetrahydrofuran (A), 2-(cyclohex-2-en-1-yl)tetrahydrofuran (B) and 2-(cyclohex-1-en-1-yl)tetrahydrofuran (C), along with gaseous hydrogen. The mechanistic study revealed that these products were formed through different individual mechanisms: successive addition of two radical species, a 2-tetrahydrofuranyl radical and a hydrogen radical, to the double bond of cyclohexene for A, coupling of a 3-cyclohexenyl radical and a 2-tetrahydrofuranyl radical for B, and 2-tetrahydrofuranyl radical addition and hydrogen radical elimination at the double bond of cyclohexene for C. Among these three mechanisms, those for B and C are dehydrogenative. In this photocatalytic reaction system, since the cyclohexene molecule has enough reactivity, due to the localized π electron density, the Pt nanoparticles loaded on the TiO2 function not as a metal catalyst but as an electron receiver to enhance the charge separation, although the dehydrogenative cross-coupling of benzene with THF requires Pd metal catalysis.
- Tyagi, Akanksha,Yamamoto, Akira,Yamamoto, Muneaki,Yoshida, Tomoko,Yoshida, Hisao
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p. 2546 - 2556
(2018/06/01)
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- Indium Catalyzed Hydrofunctionalization of Styrene Derivatives Bearing a Hydroxy Group with Organosilicon Nucleophiles
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Hydrofunctionalization is one of the most important transformation reactions of alkenes. Herein, we describe the development of an indium-triiodide-catalyzed hydrofunctionalization of alkenes bearing a hydroxy group using various types of organosilicon nucleophiles. Indium triiodide was the most effective catalyst, whereas typical Lewis acids such as TiCl4, AlCl3, and BF3·OEt2 were ineffective. Many functional groups were successfully introduced, and these resulted in yields of 31-86%. Various styrene derivatives were also applicable to this reaction. Mechanistic investigation revealed that the present hydrofunctionalization proceeded through Br?nsted acid-catalyzed intramolecular hydroalkoxylation of alkenes followed by InI3-catalyzed substitution reaction of cyclic ether intermediates.
- Kita, Yuji,Yata, Tetsuji,Nishimoto, Yoshihiro,Yasuda, Makoto
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supporting information
p. 740 - 753
(2018/01/28)
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- Cyclic ether synthesis from diols using trimethyl phosphate
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Cyclic ethers have been effectively synthesized via the intramolecular cyclization of diols using trimethyl phosphate and NaH. The present cyclization could proceed at room temperature to produce 5-7 membered cyclic ethers in good to excellent yields. Substrates possessing a chiral secondary hydroxy group were transformed into the corresponding chiral cyclic ethers along with the retention of their stereochemistries.
- Asai, Shota,Kato, Maho,Monguchi, Yasunari,Sajiki, Hironao,Sawama, Yoshinari
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supporting information
p. 4787 - 4790
(2017/07/06)
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- Glycosyl Cross-Coupling of Anomeric Nucleophiles: Scope, Mechanism, and Applications in the Synthesis of Aryl C-Glycosides
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Stereoselective manipulations at the C1 anomeric position of saccharides are one of the central goals of preparative carbohydrate chemistry. Historically, the majority of reactions forming a bond with anomeric carbon has focused on reactions of nucleophiles with saccharide donors equipped with a leaving group. Here, we describe a novel approach to stereoselective synthesis of C-aryl glycosides capitalizing on the highly stereospecific reaction of anomeric nucleophiles. First, methods for the preparation of anomeric stannanes have been developed and optimized to afford both anomers of common saccharides in high anomeric selectivities. We established that oligosaccharide stannanes could be prepared from monosaccharide stannanes via O-glycosylation with Schmidt-type donors, glycal epoxides, or under dehydrative conditions with C1 alcohols. Second, we identified a general set of catalytic conditions with Pd2(dba)3 (2.5 mol%) and a bulky ligand (JackiePhos, 10 mol%) controlling the β-elimination pathway. We demonstrated that the glycosyl cross-coupling resulted in consistently high anomeric selectivities for both anomers with mono- and oligosaccharides, deoxysugars, saccharides with free hydroxyl groups, pyranose, and furanose substrates. The versatility of the glycosyl cross-coupling reaction was probed in the total synthesis of salmochelins (siderophores) and commercial anti-diabetic drugs (gliflozins). Combined experimental and computational studies revealed that the β-elimination pathway is suppressed for biphenyl-type ligands due to the shielding of Pd(II) by sterically demanding JackiePhos, whereas smaller ligands, which allow for the formation of a Pd-F complex, predominantly result in a glycal product. Similar steric effects account for the diminished rates of cross-couplings of 1,2-cis C1-stannanes with aryl halides. DFT calculations also revealed that the transmetalation occurs via a cyclic transition state with retention of configuration at the anomeric position. Taken together, facile access to both anomers of various glycoside nucleophiles, a broad reaction scope, and uniformly high transfer of anomeric configuration make the glycosyl cross-coupling reaction a practical tool for the synthesis of bioactive natural products, drug candidates, allowing for late-stage glycodiversification studies with small molecules and biologics.
- Zhu, Feng,Rodriguez, Jacob,Yang, Tianyi,Kevlishvili, Ilia,Miller, Eric,Yi, Duk,O'Neill, Sloane,Rourke, Michael J.,Liu, Peng,Walczak, Maciej A.
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supporting information
p. 17908 - 17922
(2017/12/26)
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- An efficient method for the reductive conversion of acyclic esters to ethers via a TMS-protected acetal
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We report an efficient two step process for the reduction of non-aromatic esters to the corresponding ethers via the intermediate TMS-protected acetal. The acetal formed after the first step can be carried on directly to the subsequent reduction to the ether without purification. The ester reduction step was monitored using in-situ ReactIR for disappearance of the C[dbnd]O peak, allowing for the exact determination of time and equivalents of the reducing agent. Furthermore, use of TMS-imidazole to form the acetal has allowed us to dramatically reduce the overall reaction time required for the two step procedure.
- Hart, Alison,Kelley, Sarah A.,Harless, Tyler,Hood, John A.,Tagert, Michael,Pigza, Julie A.
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supporting information
p. 3024 - 3027
(2017/07/17)
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- Niobium-Catalyzed Intramolecular Addition of O-H and N-H Bonds to Alkenes: A Tool for Hydrofunctionalization
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A convenient, versatile, and easy to handle intramolecular hydrofunctionalization of alkenes (C-O and C-N bonds formation) is reported using a novel niobium-based catalytic system. This atom economic and eco-friendly methodology provides an additional synthetic tool for the straightforward formation of valuable building blocks enabling molecular complexity. Various pyran, furan, pyrrolidine, piperidine, lactone, and lactam derivatives as well as spirocyclic compounds are produced in high yields and selectivities.
- Ferrand, Laura,Tang, Yue,Aubert, Corinne,Fensterbank, Louis,Mouriès-Mansuy, Virginie,Petit, Marc,Amatore, Muriel
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supporting information
p. 2062 - 2065
(2017/04/28)
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- Preparation of arylmagnesium/lithium from aryl bromides and their coupling and substitution reactions in tetrahydrofuran
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One-pot synthesis of 2-aryltetrahydrofurans was achieved by a coupling reaction between arylmagnesium bromides prepared in situ and tetrahydrofuran under mild conditions. The reaction between ArBr and n-BuLi gave unexpected butylbenzene derivatives in mod
- Gundogdu, Ozlem,Altundas, Ramazan,Kara, Yunus
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- A combined computational and experimental investigation of the oxidative ring-opening of cyclic ethers by oxoammonium cations
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The propensity of oxoammonium cations to facilitate the oxidative ring-opening of cyclic ethers to their corresponding distal hydroxy ketones is investigated. The reaction has been evaluated using experimental and computational methods to gain deeper insight into trends in reactivity.
- Loman, Jacob. J.,Carnaghan, Emma R.,Hamlin, Trevor A.,Ovian, John M.,Kelly, Christopher B.,Mercadante, Michael A.,Leadbeater, Nicholas E.
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p. 3883 - 3888
(2016/05/24)
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- Redox-Active Esters in Fe-Catalyzed C-C Coupling
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Cross-couplings of alkyl halides and organometallic species based on single electron transfer using Ni and Fe catalyst systems have been studied extensively, and separately, for decades. Here we demonstrate the first couplings of redox-active esters (both isolated and derived in situ from carboxylic acids) with organozinc and organomagnesium species using an Fe-based catalyst system originally developed for alkyl halides. This work is placed in context by showing a direct comparison with a Ni catalyst for >40 examples spanning a range of primary, secondary, and tertiary substrates. This new C-C coupling is scalable and sustainable, and it exhibits a number of clear advantages in several cases over its Ni-based counterpart.
- Toriyama, Fumihiko,Cornella, Josep,Wimmer, Laurin,Chen, Tie-Gen,Dixon, Darryl D.,Creech, Gardner,Baran, Phil S.
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p. 11132 - 11135
(2016/10/12)
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- Triphenylphosphine-N-bromosuccinimide mediated chemoselective cyclodehydration of diols
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A triphenylphosphine-N-bromosuccinimide mediated chemoselective cyclodehydration of diols is presented for the synthesis of polysubstituted tetrahydrofurans. 1,4-Diols and their derivatives can be rapidly cyclized to furnish tetrahydrofurans in high yields with one equivalent of Ph3P/NBS. Higher amount of Ph3P/NBS leads to the formation of dibromobutanes.
- Zhao, Shuo,Wu, You,Sun, Qi,Cheng, Tie-Ming,Li, Run-Tao
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p. 1154 - 1162
(2015/04/14)
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- Br?nsted Acid-Catalyzed Intramolecular Nucleophilic Substitution of the Hydroxyl Group in Stereogenic Alcohols with Chirality Transfer
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The hydroxyl group of enantioenriched benzyl, propargyl, allyl, and alkyl alcohols has been intramolecularly displaced by uncharged O-, N-, and S-centered nucleophiles to yield enantioenriched tetrahydrofuran, pyrrolidine, and tetrahydrothiophene derivatives with phosphinic acid catalysis. The five-membered heterocyclic products are generated in good to excellent yields, with high degree of chirality transfer, and water as the only side-product. Racemization experiments show that phosphinic acid does not promote SN1 reactivity. Density functional theory calculations corroborate a reaction pathway where the phosphinic acid operates as a bifunctional catalyst in the intramolecular substitution reaction. In this mechanism, the acidic proton of the phosphinic acid protonates the hydroxyl group, enhancing the leaving group ability. Simultaneously, the oxo group of phosphinic acid operates as a base abstracting the nucleophilic proton and thus enhancing the nucleophilicity. This reaction will open up new atom efficient techniques that enable alcohols to be used as nucleofuges in substitution reactions in the future.
- Bunrit, Anon,Dahlstrand, Christian,Olsson, Sandra K.,Srifa, Pemikar,Huang, Genping,Orthaber, Andreas,Sj?berg, Per J. R.,Biswas, Srijit,Himo, Fahmi,Samec, Joseph S. M.
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supporting information
p. 4646 - 4649
(2015/04/27)
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- Concise, stereodivergent and highly stereoselective synthesis of cis-and trans-2-substituted 3-hydroxypiperidines-development of a phosphite-driven cyclodehydration
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A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.
- Huy, Peter H.,Westphal, Julia C.,Koskinen, Ari M.P.
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supporting information
p. 369 - 383
(2014/03/21)
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- Asymmetric hydrogenation of disubstituted furans
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An enantioselective hydrogenation of disubstituted furans has been developed by using a chiral ruthenium catalyst with N-heterocyclic carbene ligands. This reaction converts furans into valuable enantioenriched disubstituted tetrahydrofurans.
- Wysocki, Jedrzej,Ortega, Nuria,Glorius, Frank
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supporting information
p. 8751 - 8755
(2014/08/18)
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- Practical and highly selective C-H functionalization of structurally diverse ethers
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A trityl ion mediated C-H functionalization of ethers with a wide range of nucleophiles at ambient temperature has been developed. The reaction displays high chemo-selectivity and good functional group tolerance. The protocol also exhibits excellent regio- and diastereoselectivities for the unsymmetric ethers, thus stereoselectively generating highly functionalized disubstituted 2,5-trans tetrahydrofurans (THF), 2,6-trans tetrahydropyrans (THP), 2,6-trans dihydropyrans (DHP), and 1,3-trans isochromans, and highlighting the capacity of the protocol in complex molecule synthesis.
- Wan, Miao,Meng, Zhilin,Lou, Hongxiang,Liu, Lei
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supporting information
p. 13845 - 13849
(2015/01/16)
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- Ruthenium-porphyrin-catalyzed diastereoselective intramolecular alkyl carbene insertion into C-H bonds of alkyl diazomethanes generated in situ from N-tosylhydrazones
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With a ruthenium-porphyrin catalyst, alkyl diazomethanes generated in situ from N-tosylhydrazones efficiently underwent intramolecular C(sp3)-H insertion of an alkyl carbene to give substituted tetrahydrofurans and pyrrolidines in up to 99% yield and with up to 99:1 cis selectivity. The reaction displays good tolerance of many functionalities, and the procedure is simple without the need for slow addition with a syringe pump. From a synthetic point of view, the C-H insertion of N-tosylhydrazones can be viewed as reductive coupling between a C=O bond and a C-H bond to form a new C-C bond, since N-tosylhydrazones can be readily prepared from carbonyl compounds. This reaction was successfully applied in a concise synthesis of (-)-pseudoheliotridane.
- Reddy, Annapureddy Rajasekar,Zhou, Cong-Ying,Guo, Zhen,Wei, Jinhu,Che, Chi-Ming
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p. 14175 - 14180
(2015/01/09)
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- Nickel complex catalyzed efficient activation of sp3and sp 2c-h bonds for alkylation and arylation of oxygen containing heterocyclic molecules
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A nickel(II) complex (1) of N,N'-bis(2,6-diisopropylphenyl)-2,6- pyridinedicarboxamido (L) ligand was examined for catalytic coupling of Grignard reagents with the C-H bond of oxygen containing heterocyclic compounds such as tetrahydrofuran and furan. The nickel( II) complex showed excellent activity in catalyzing C-H activation and further coupling with various Grignard reagents. The effective activation of the C-H bond proceeded under ambient reaction conditions with a short reaction time (1-2 h). The catalyst (1) displays high turnover frequency of 4,130 h-1with catalyst loading as low as 0.01 mol%. This catalytic route could prove to be an efficient mode of activation of sp3and sp2C-H bonds in various heterocycles for the preparation of synthetically and pharmaceutically relevant molecules. Springer Science+Business Media New York 2013.
- Gartia, Yashraj,Ramidi, Punnamchandar,Jones, Darin E.,Pulla, Sharon,Ghosh, Anindya
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p. 507 - 515
(2014/06/24)
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- Activation of sp3 and sp2 C-H bonds of oxygen containing heterocyclic molecules for alkylation and arylation reactions catalyzed by an iron complex
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Activation of both sp3 and sp2 CH bonds is reported using an efficient iron(III) complex (1) of a ligand (N2,N6-bis(2,6- diisopropylphenyl)pyridine-2,6-dicarboxamide: L). The iron(III) complex showed catalytic activity of CC coupling reaction of oxygen containing heterocycles, e.g. tetrahydrofuran (THF), with various alkyl, allyl and aryl Grignard reagents under ambient reaction conditions. Complex 1 demonstrated excellent activity and reactions were completed within 30 min to 1 h. A high turnover frequency (TOF) of 1700 h-1 using a low catalyst loading of 0.02 mol% was obtained for the reaction. Interestingly, the catalyst was selective in activation of the CH bond adjacent to the oxygen in various oxygen containing heterocyclic molecules to yield 2-substitituted products.
- Gartia, Yashraj,Ramidi, Punnamchandar,Cheerla, Sreevishnu,Felton, Charlette M.,Jones, Darin E.,Das, Bhaskar C.,Ghosh, Anindya
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p. 253 - 259
(2014/07/07)
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- Iron-catalyzed allylic arylation of olefins via C(sp3)-H activation under mild conditions
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An aryl Grignard reagent in the presence of mesityl iodide converts an allylic C-H bond of a cycloalkene or an allylbenzene derivative into a C-C bond in the presence of a catalytic amount of Fe(acac)3 and a diphosphine ligand at 0 C. The stereo- and regioselectivity of the reaction, together with deuterium labeling experiments, suggest that C-H bond activation is the slow step in the catalytic cycle preceding the formation of an allyliron intermediate.
- Sekine, Masaki,Ilies, Laurean,Nakamura, Eiichi
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supporting information
p. 714 - 717
(2013/04/10)
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- Bronsted acid catalyzed asymmetric SN2-Type O-alkylations
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Bridging the gap: Bronsted acids catalyze an intramolecular S N2-type alkylation of alcohols with ethers by bridging a pentacoordinate transition state, thus simultaneously activating both the leaving group and nucleophile (see scheme). Density functional calculations provide detailed insight into the course of the reaction and the transition-state structure.
- Coric, Ilija,Kim, Ji Hye,Vlaar, Tjostil,Patil, Mahendra,Thiel, Walter,List, Benjamin
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supporting information
p. 3490 - 3493
(2013/05/09)
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- Efficient, stereodivergent access to 3-piperidinols by traceless P(OEt)3 cyclodehydration
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A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a "traceless" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is developed.
- Huy, Peter H.,Koskinen, Ari M. P.
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supporting information
p. 5178 - 5181
(2013/11/06)
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- Selective synthesis of unsymmetrical ethers from different alcohols catalyzed by sodium bisulfite
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An efficient method for the preparation of unsymmetrical ethers from alcohols catalyzed by sodium bisulfite is reported. The procedure enables the direct dehydration of primary, secondary, and tertiary benzylic alcohols with aliphatic alcohols in the abse
- Yu, Jun-Lai,Wang, Hui,Zou, Kai-Feng,Zhang, Jia-Rui,Gao, Xiang,Zhang, Dan-Wei,Li, Zhan-Ting
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p. 310 - 315
(2013/01/15)
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- Asymmetric 5-endo chloroetherification of homoallylic alcohols toward the synthesis of chiral β-chlorotetrahydrofurans
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An asymmetric 5-endo chloroetherification of homoallylic alcohols is successfully developed that employs an easily available quaternary ammonium salt derived from cinchonine as a conventional organocatalyst. This approach provides ready access to β-chloro
- Zeng, Xianghua,Miao, Chengxia,Wang, Shoufeng,Xia, Chungu,Sun, Wei
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p. 2418 - 2420
(2013/04/10)
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- Gated access to α-lithiated phenyltetrahydrofuran: Functionalisation via direct lithiation of the parent oxygen heterocycle
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Cycloreversion of α-lithiated phenyltetrahydrofuran was successfully tamed at -78 °C in a non-coordinating solvent in the presence of TMEDA. This anion showed excellent nucleophilicity and could be intercepted with a variety of structurally different electrophiles to give 2,2-disubstituted derivatives which can be further elaborated to γ-butyrolactones. The Royal Society of Chemistry 2013.
- Mansueto, Rosmara,Mallardo, Valentina,Perna, Filippo Maria,Salomone, Antonio,Capriati, Vito
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p. 10160 - 10162
(2013/10/22)
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- Direct functionalization of tetrahydrofuran and 1,4-dioxane: Nickel-catalyzed oxidative C(sp3)-H arylation
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CHoose nickel: The nickel-catalyzed oxidative arylation of C(sp 3)-H bonds has been achieved. Several substituted arylboronic acids and various C(sp3)-H bonds were found to be suitable substrates for this novel transformation, which is likely to proceed through a radical pathway. This method allows the introduction of simple ether derivatives to construct α-arylated ethers. FG=functional group. Copyright
- Liu, Dong,Liu, Chao,Li, Heng,Lei, Aiwen
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supporting information
p. 4453 - 4456
(2013/05/21)
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- O-alkyl-N-acyl-N-phenylhydroxylamines as photochemical alkoxy radical precursors
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A simple and efficient technique for the photolysis of alkoxy radical precursors is developed. Irradiation of O-alkyl-N-acyl-N-phenylhydroxylamines, as representative alkoxy radical precursors, with ultraviolet light (254 nm) results in homolytic N-O bond cleavage to generate singlet alkoxy and acylaminyl caged radical pairs. These radicals, depending on the solvent employed, either escape from the cage to form fragmentation products, or undergo in-cage reactions to produce photorearrangement products. The homolytic cleavage of the N-O bond is analyzed using time-dependent density functional theory calculations. The nature of the N-acyl substituent on the O-alkyl-N-acyl-N- phenylhydroxylamines is shown to influence their ability to generate radicals. Furthermore, identification and trapping of the alkoxy radicals is demonstrated. Georg Thieme Verlag Stuttgart · New York.
- Chowdhury, Nilanjana,Anoop, Anakuthil,Singh, N.D. Pradeep
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p. 1745 - 1754
(2012/07/27)
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- One-pot asymmetric synthesis of 2-and 2,3-disubstituted tetrahydrofuran derivatives
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A novel and convenient one-pot asymmetric synthesis of 2- and 2,3-disubstituted tetrahydrofurans has been achieved in 56-81% yields and 86-99% ee from aliphatic and aromatic aldehydes via an allyl/crotyl/ alkoxyallylboration-hydroboration-iodination-cyclization reaction sequence.
- Ramachandran, P. Veeraraghavan,Nair, Hari N. G.,Gagare, Pravin D.
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p. 5394 - 5398
(2012/08/07)
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- New method for C-H arylation/alkylation at α-position of cyclic aliphatic ethers by iron-oxide mediated reaction
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We report a new and efficient iron oxide catalyzed cross-coupling reaction between organometallic species such as alkyl/arylmagnesium halides or organolithium species and α-hydrogen bearing cyclic unbranched and branched aliphatic ethers via activation of C(sp3)-H. In the presence of 1 mol% of iron oxide, five and six membered unbranched cyclic ethers such as tetrahydrofuran and tetrahydropyran gave good to excellent yields of cross-coupled products. Whereas, in case of branched ether such as 2-methyltetrahydrofuran, it was observed that the arylation occurred at both the sides and gave moderate yields of a mixture of regioisomers. Among the organometallic species used, alkyl organometallic reagents gave less yields as compared to aryl organometallics.
- Singh, Parvinder Pal,Gudup, Satish,Aruri, Hariprasad,Singh, Umed,Ambala, Srinivas,Yadav, Mahipal,Sawant, Sanghapal D.,Vishwakarma, Ram A.
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experimental part
p. 1587 - 1597
(2012/03/22)
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- Cyclopropenium-activated cyclodehydration of diols
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The dehydrative cyclization of diols to cyclic ethers via cyclopropenium activation is described. Using 2,3-diphenylcyclopropene and methanesulfonic anhydride, a series of 1,4-and 1,5-diols are rapidly cyclized to furnish tetrahydrofurans and tetrahydropyrans in high yield. Eleven total substrates are shown, including a gram scale cyclization of a diterpene derivative.
- Kelly, Brendan D.,Lambert, Tristan H.
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supporting information; experimental part
p. 740 - 743
(2011/05/04)
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- Iron oxide mediated direct C-H arylation/alkylation at α-position of cyclic aliphatic ethers
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We report a new and efficient iron oxide catalyzed cross-coupling reaction between organometallic species such as alkyl/arylmagnesium halides or organolithium species and α-hydrogen bearing cyclic aliphatic ethers via activation of C(sp3)-H. This is the first example of iron oxide mediated direct C-C bond formation without expensive or toxic ligands.
- Singh, Parvinder Pal,Gudup, Satish,Ambala, Srinivas,Singh, Umed,Dadhwal, Sumit,Singh, Baldev,Sawant, Sanghapal D.,Vishwakarma, Ram A.
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supporting information; experimental part
p. 5852 - 5854
(2011/06/26)
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- An investigation into the one-pot Heck olefination-hydrogenation reaction
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Herein is described an operationally simple process concerning the observation that, following either inter-, or intramolecular Heck olefination, stirring of the so formed substituted alkenyl product under an atmosphere of hydrogen efficiently effects alkene hydrogenation. Overall this two-operation, one-pot "reductive Heck" sequence is notable since direct reductive Heck processes, using additives such as formate salts, are restricted to a limited range of substrates. In total 25 examples are reported (yields ranging from 0 to 95%), which were selected in order to probe the scope and limitations of this method. Finally, the utility of this sequence was demonstrated in a short synthesis of the calcimimetic agent, cinacalcet.
- Geoghegan, Kimberly,Kelleher, Susan,Evans, Paul
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experimental part
p. 2187 - 2194
(2011/05/14)
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- Efficiency of alkoxyl radical product formation from 5-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones
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In a comparative study, reactions between 5-(p-methoxyphenyl)-substituted 3-alkoxy-4-methylthiazole-2(3H)-thiones and appropriate mediators (BrCCl3, Bu3SnH) provided higher yields of alkoxyl radical products (δ-bromohydrins, cyclic ethers, carbonyl compounds) than respective transformations of 5-phenyl- and 5-methyl-substituted derivatives. The unusual selectivity of applied thiohydroxamates to furnish products of O-alkylation, even upon treatment with soft carbon electrophiles, and the marked propensity of 3-alkoxy-5-(p-methoxyphenyl)-4-methylthiazole-2(3H)-thiones to crystallize, facilitated preparation and purification of the new family of alkoxyl radical precursors in a noteworthy manner.
- Hartung, Jens,Schur, Christine,Kempter, Irina,Gottwald, Thomas
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experimental part
p. 1365 - 1374
(2010/04/04)
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- Gold-catalysed cyclic ether formation from diols
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Gold(I) and (III) salts have been found to be highly effective at the catalysis of ether formation from alcohols. Intramolecular ether formation of a 1,5-diol was also achieved, with a stereoselectivity that indicates that an SN1 mechanism predominates. In an attempt to form a seven-membered ring, a stable 14-membered dimer product was also formed. Attempts to control the diastereoselectivity of the reaction using a chiral anionic counterion did not give products with a high de.
- Jiang, Xiaolu,London, Emma K.,Morris, David J.,Clarkson, Guy J.,Wills, Martin
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experimental part
p. 9828 - 9834
(2011/02/23)
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- Stereospecific consecutive epoxide ring expansion with dimethylsulfoxonium methylide
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Figure presented. Consecutive ring-expansion reactions of oxiranes with dimethylsulfxonium methylide were studied experimentally and modeled computationally at the density functional theory (DFT) and second-order Moller-Plesset (MP2) levels of theory utilizing a polarizable continuum model (PCM) to account for solvent effects. While the epoxide to oxetane ring expansion requires 13-17 kcal mol-1 activation and occurs at elevated temperatures, the barriers for the ring expansions to oxolanes are higher (ca. 25 kcal mol-1) and require heating to 125 °C. Further expansions of these oxolanes to the six-membered oxanes are hampered by high barriers (ca. 40 kcal mol-1). We observe the complete conservation of the enantiomeric purities for the nucleophilic ring expansions of enantiomeric 2-mono- and 2,2-disubstituted epoxides and oxetanes with dimethylsulfoxonium methylide. This is a convenient general approach for the high-yielding preparation of optically active four- and five-membered cyclic ethers from oxiranes.
- Butova, Ekaterina D.,Barabash, Anastasiya V.,Petrova, Anna A.,Kleiner, Christian M.,Schreiner, Peter R.,Fokin, Andrey A.
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experimental part
p. 6229 - 6235
(2010/11/18)
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