- Chemical strategies to modify amyloidogenic peptides using iridium(iii) complexes: Coordination and photo-induced oxidation
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Amyloidogenic peptides are considered central pathological contributors towards neurodegeneration as observed in neurodegenerative disorders [e.g., amyloid-β (Aβ) peptides in Alzheimer's disease (AD)]; however, their roles in the pathologies of such diseases have not been fully elucidated since they are challenging targets to be studied due to their heterogeneous nature and intrinsically disordered structure. Chemical approaches to modify amyloidogenic peptides would be valuable in advancing our molecular-level understanding of their involvement in neurodegeneration. Herein, we report effective chemical strategies for modification of Aβ peptides (i.e., coordination and coordination-/photo-mediated oxidation) implemented by a single Ir(iii) complex in a photo-dependent manner. Such peptide variations can be achieved by our rationally designed Ir(iii) complexes (Ir-Me, Ir-H, Ir-F, and Ir-F2) leading to significantly modulating the aggregation pathways of two main Aβ isoforms, Aβ40 and Aβ42, as well as the production of toxic Aβ species. Overall, we demonstrate chemical tactics for modification of amyloidogenic peptides in an effective and manageable manner utilizing the coordination capacities and photophysical properties of transition metal complexes.
- Kang, Juhye,Nam, Jung Seung,Lee, Hyuck Jin,Nam, Geewoo,Rhee, Hyun-Woo,Kwon, Tae-Hyuk,Lim, Mi Hee
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Read Online
- Automated iterative Csp 3–C bond formation
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Fully automated synthetic chemistry would substantially change the field by providing broad?on-demand?access to small molecules. However, the reactions that can be run autonomously are still limited. Automating the stereospecific assembly of Csp3–C bonds would expand access to many important types of?functional organic molecules1. Previously, methyliminodiacetic acid (MIDA) boronates were used to orchestrate the formation of Csp2–Csp2 bonds and were effective building blocks for automating the synthesis of many small molecules2, but they are incompatible with stereospecific Csp3–Csp2 and Csp3–Csp3 bond-forming reactions3–10. Here we report that hyperconjugative and steric tuning provide a new class of tetramethyl N-methyliminodiacetic acid (TIDA) boronates that are stable to these conditions. Charge density analysis11–13 revealed that redistribution of electron density increases covalency of the N–B bond and thereby attenuates its hydrolysis. Complementary steric shielding of carbonyl π-faces decreases reactivity towards nucleophilic reagents. The unique features of the iminodiacetic acid cage2, which are essential for generalized automated synthesis, are retained by TIDA boronates. This enabled Csp3 boronate building blocks to be assembled using automated synthesis, including the preparation of natural products through automated stereospecific Csp3–Csp2 and Csp3–Csp3 bond formation. These findings will enable increasingly complex Csp3-rich small molecules to be accessed via automated assembly.
- Ballmer, Steve G.,Blair, Daniel J.,Burke, Martin D.,Chitti, Sriyankari,Gill, Adrian L.,Gray, Danielle L.,Haley, Hannah M. S.,Hansen, Richard L.,Kostyra, David M.,Morehouse, Greg. F.,Mubayi, Vikram,Palazzolo Ray, Andrea M. E.,Pipal, Robert W.,Schmidt, Michael J.,Trobe, Melanie,Wang, Wesley,Woods, Toby J.
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- Asymmetric 1,4-Addition of Arylboronic Acids to β,γ-Unsaturated α-Ketoesters using Heterogeneous Chiral Metal Nanoparticle Systems
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Asymmetric 1,4-addition reactions with β,γ-unsaturated α-ketoesters are valuable because the resulting chiral ketoester compounds can be converted into various useful species that are often used as chiral building blocks in drug and natural product synthesis. However, β,γ-unsaturated α-ketoesters have two reactive points in terms of nucleophilic additions, which will lead to the 1,4-adduct, the 1,2-adduct and to the combined 1,4- and 1,2-adduct. Therefore, controlling this chemoselectivity is an important factor for the development of these transformations. Here, we developed an asymmetric 1,4-addition of aryl boronic acids to β,γ-unsaturated α-ketoesters by using heterogeneous chiral rhodium nanoparticle systems with a chiral diene ligand bearing a secondary amide moiety. The newly developed polydimethylsilane-immobilized rhodium nanoparticle catalysts showed high activity, high chemoselectivity, and excellent enantioselectivity, and this is the first heterogeneous catalytic system for this asymmetric reaction. Metal nanoparticle catalysts were recovered and reused without loss of activity or leaching of metal. (Figure presented.).
- Miyamura, Hiroyuki,Yasukawa, Tomohiro,Zhu, Zhiyuan,Kobayashi, Shū
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supporting information
p. 353 - 359
(2019/12/15)
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- Aryl boronic acid preparation method
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The invention belongs to the technical field of fine chemical engineering, and relates to an aryl boronic acid preparation method. In the prior art, aryl boronic acid as a novel safe and environmentally-friendly arylation reagent is widely used in scientific research and production of various fine chemicals containing aryl structures in the fields of medicines, pesticides, advanced materials and the like; and the aryl boronic acid compound preparation method reported in the disclosed literature has problems of harsh reaction conditions and high cost. A purpose of the invention is to provide amethod, wherein an aryl boron compound is formed by carrying out a reaction on a Grignard reagent and trialkyl borate under mild conditions, the composition of the aryl boron compound is converted from the main component diaryl borate into the main component aryl borate, and the aryl borate is hydrolyzed to obtain aryl boric acid, so that the preparation cost of the acyl aryl boric acid compound can be remarkably reduced, and the method has good practical application prospect.
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Paragraph 0033-0036; 0040-0041
(2020/01/25)
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- Transition-Metal-Free Borylation of Aryl Bromide Using a Simple Diboron Source
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In this study, we developed a simple transition-metal-free borylation reaction of aryl bromides. Bis-boronic acid (BBA), was used, and the borylation reaction was performed using a simple procedure at a mild temperature. Under mild conditions, aryl bromides were converted to arylboronic acids directly without any deprotection steps and purified by conversion to trifluoroborate salts. The functional group tolerance was considerably high. The mechanism study suggested that this borylation reaction proceeds via a radical pathway.
- Han, Min Su,Lim, Taeho,Ryoo, Jeong Yup
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p. 10966 - 10972
(2020/09/23)
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- IRIDIUM COMPLEX, COMPOSITION HAVING THE SAME, AND USE THEREOF
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The present invention relates to an iridium complex which is a compound represented by chemical formula 1, a composition comprising an iridium complex, and uses thereof. In the chemical formula 1, R^1 to R^8, and A are as defined in claim 1. The present invention can provide the iridium complex that can be effectively applied to the regulation of amyloid beta peptide aggregation.(AA) [Strategy 1] Inhibition(BB) [Strategy 2] OxidationCOPYRIGHT KIPO 2020
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Paragraph 0090-0092
(2020/04/16)
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- Magnesium promoted autocatalytic dehydrogenation of amine borane complexes: A reliable, non-cryogenic, scalable access to boronic acids
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Owing to the unusual reactivity of dialkylamine-borane complexes, a methodology was developed to simply access boronic acids. The intrinsic instability of magnesium aminoborohydride was tweaked into a tandem dehydrogenation borylation sequence. Proceeding via an autocatalytic cycle, amineborane dehydrogenation was induced by a variety of Grignard reagents. Overall, addition of the organomagnesium species onto specially designed dialkylamine-borane complexes led to a variety of boronic acids in high yields. In addition, the reaction can be performed under Barbier conditions, on a large scale.
- Marciasini, Ludovic D.,Richard, Jimmy,Cacciuttolo, Bastien,Sartori, Guillaume,Birepinte, Melodie,Chabaud, Laurent,Pinet, Sandra,Pucheault, Mathieu
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p. 164 - 171
(2018/12/05)
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- An efficient method for the hydrolysis of potassium organotrifluoroborates promoted by montmorillonite K10
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An efficient and non-expensive method for conversion of diverse potassium organotrifluoroborates to their corresponding boronic acids promoted by montmorillonite K10 using water as the reaction solvent is described. Further interconversion of potassium organotrifluoroborates to their corresponding boronic esters, via boronic acid intermediates was also successfully accomplished. The products were obtained in good yields, being the rate of hydrolysis influenced by the type of substituent present in the boronic acid.
- Silva, Renato L.,Santos, Cosme S.,Santos, Jonh A. M.,Oliveira, Roberta A.,Menezes, Paulo H.,Freitas, Juliano C. R.
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p. 1777 - 1785
(2018/09/04)
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- Copper-Catalyzed Monoorganylation of Trialkyl Borates with Functionalized Organozinc Pivalates
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Organozinc pivalates, a recently developed air- and moisture-stable organozinc species, were found for the first time as excellent organometallic species in the monoorganylation of trialkyl borates whereby boronic acids were prepared in high yields. The significant advantage of organozinc pivalates over another previously employed organometallic reagents, e. g., organolithium reagents, Grignard reagents and organozinc halides, is that the generation of multiorganylation byproducts such as borinic acids and trialkylboranes were completely suppressed. Additionally, the in situ generated boronates could be directly arranged into Suzuki-Miyaura type cross-coupling reactions to produce biaryls in high yields.
- Fu, Ying,Gou, Bei-Lei,Shi, Chun-Zhao,Du, Zhengyin,Shen, Tong
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p. 4253 - 4257
(2018/09/18)
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- Photoinduced Miyaura Borylation by a Rare-Earth-Metal Photoreductant: The Hexachlorocerate(III) Anion
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The first photoinduced carbon(sp2)–heteroatom bond forming reaction by a rare-earth-metal photoreductant, a Miyaura borylation, has been achieved. This simple, scalable, and novel borylation method that makes use of the hexachlorocerate(III) anion ([CeIIICl6]3?, derived from CeCl3) has a broad substrate scope and functional-group tolerance and can be conducted at room temperature. Combined with Suzuki–Miyaura cross-coupling, the method is applicable to the synthesis of various biaryl products, including through the use of aryl chloride substrates.
- Qiao, Yusen,Yang, Qiaomu,Schelter, Eric J.
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supporting information
p. 10999 - 11003
(2018/07/31)
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- PROTECTED ORGANOBORONIC ACIDS WITH TUNABLE REACTIVITY, AND METHODS OF USE THEREOF
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Disclosed are a range of protected organoboronic acid reagents useful in the modular assembly of complex organic compounds. The reactivities of the protected organoboronic acid reagents may be varied predictably by changes to the number and identities of their substituents. Also disclosed are methods of using the protected organoboronic acid reagents in the synthesis of organic compounds.
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- Structural, Kinetic, and Computational Characterization of the Elusive Arylpalladium(II)boronate Complexes in the Suzuki-Miyaura Reaction
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The existence of the oft-invoked intermediates containing the crucial Pd-O-B subunit, the “missing link”, has been established in the Suzuki-Miyaura cross-coupling reaction. The use of low-temperature, rapid injection NMR spectroscopy (RI-NMR), kinetic studies, and computational analysis has enabled the generation, observation, and characterization of these highly elusive species. The ability to confirm the intermediacy of Pd-O-B-containing species provided the opportunity to clarify mechanistic aspects of the transfer of the organic moiety from boron to palladium in the key transmetalation step. Specifically, these studies establish the identity of two different intermediates containing Pd-O-B linkages, a tri-coordinate (6-B-3) boronic acid complex and a tetra-coordinate (8-B-4) boronate complex, both of which undergo transmetalation leading to the cross-coupling product. Two distinct mechanistic pathways have been elucidated for stoichiometric reactions of these complexes: (1) transmetalation via an unactivated 6-B-3 intermediate that dominates in the presence of an excess of ligand, and (2) transmetalation via an activated 8-B-4 intermediate that takes place with a deficiency of ligand.
- Thomas, Andy A.,Wang, Hao,Zahrt, Andrew F.,Denmark, Scott E.
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supporting information
p. 3805 - 3821
(2017/03/20)
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- Development of a Concise Multikilogram Synthesis of LPA-1 Antagonist BMS-986020 via a Tandem Borylation-Suzuki Procedure
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The process development for the synthesis of BMS-986020 (1) via a palladium catalyzed tandem borylation/Suzuki reaction is described. Evaluation of conditions culminated in an efficient borylation procedure using tetrahydroxydiboron followed by a tandem Suzuki reaction employing the same commercially available palladium catalyst for both steps. This methodology addressed shortcomings of early synthetic routes and was ultimately used for the multikilogram scale synthesis of the active pharmaceutical ingredient 1. Further evaluation of the borylation reaction showed useful reactivity with a range of substituted aryl bromides and iodides as coupling partners. These findings represent a practical, efficient, mild, and scalable method for borylation.
- Smith, Michael J.,Lawler, Michael J.,Kopp, Nathaniel,McLeod, Douglas D.,Davulcu, Akin H.,Lin, Dong,Katipally, Kishta,Sfouggatakis, Chris
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p. 1859 - 1863
(2017/11/24)
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- Synthesis of 3-amino-4-fluorophenylboronic acid method
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The invention belongs to the field of synthesis of organic chemicals, and relates to a method for synthesizing 3-amino-4-fluorophenylboronic acid, which comprises the following steps: 1. preparing fluorobromobenzene into a Grignard reagent, and reacting with trimethyl borate to obtain an intermediate fluorophenylboronic acid A; 2. reacting the intermediate A with fuming nitric acid to generate an intermediate 3-nitro-4-fluorophenylboronic acid B; and 3. hydrogenating the intermediate B by using a palladium-on-carbon catalyst to generate the product 3-amino-4-fluorophenylboronic acid C. The synthesis method has the advantages of accessible raw materials and lower cost, is simple to operate, and provides a proper way for preparing 3-amino-4-fluorophenylboronic acid.
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Paragraph 0024; 0028
(2017/02/09)
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- Asymmetric Arylation of Imines Catalyzed by Heterogeneous Chiral Rhodium Nanoparticles
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Asymmetric arylation of aldimines catalyzed by heterogeneous chiral rhodium nanoparticles has been developed. The reaction proceeded in aqueous media without significant decomposition of the imines by hydrolysis to afford chiral (diarylmethyl)amines in high yields with outstanding enantioselectivities. This catalyst system exhibited the highest turnover number (700) in heterogeneous catalysts reported to date for these reactions. The reusability of the catalyst was also demonstrated.
- Yasukawa, Tomohiro,Kuremoto, Tatsuya,Miyamura, Hiroyuki,Kobayashi, Sh?
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supporting information
p. 2716 - 2718
(2016/06/15)
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- Method for synthesizing 2-(4-fluorophenyl) thiophene
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The invention discloses a method for synthesizing 2-(4-fluorophenyl) thiophene. The method comprises the following steps: 1) preparing 4-fluorophenylboronic acid: separately preserving heat for a 4-fluorophenylmagnesium bromide solution which is taken as a material 1 and a boric acid ester solution which is taken as a material 2 to the reaction temperature, carrying out mixing reaction, and carrying quenching and post-treatment to obtain 4-fluorophenylboronic acid; and 2) preparing 2-(4-fluorophenyl) thiophene): adding the 4-fluorophenylboronic acid, 2-bromo thiophene and a Pd catalyst into an organic solvent to dissolve to obtain a material 3, separately preserving the heat for the material 3 and an inorganic alkali aqueous solution which is taken as a material 4 to the reaction temperature, carrying out mixing reaction, and carrying out post-treatment to obtain 2-(4-fluorophenyl) thiophene. The method is simple in operation process, is short in production period, is gentle in condition, is fewer in side reactions and is high in yield; and the obtained product is high in purity.
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Paragraph 0041; 0042; 0043; 0044; 0045
(2016/12/16)
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- Spectroscopic and computational investigations of the thermodynamics of boronate ester and diazaborole self-assembly
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The solution phase self-assembly of boronate esters, diazaboroles, oxathiaboroles, and dithiaboroles from the condensation of arylboronic acids with aromatic diol, diamine, hydroxythiol, and dithiol compounds in chloroform has been investigated by 1H NMR spectroscopy and computational methods. Six arylboronic acids were included in the investigations with each boronic acid varying in the substituent at its 4-position. Both computational and experimental results show that the para-substituent of the arylboronic acid does not significantly influence the favorability of forming a condensation product with a given organic donor. The type of donor, however, greatly influences the favorability of self-assembly. 1H NMR spectroscopy indicates that condensation reactions between arylboronic acids and catechol to give boronate esters are the most favored thermodynamically, followed by diazaborole formation. Computational investigations support this conclusion. Neither oxathiaboroles nor dithiaboroles form spontaneously at equilibrium in chloroform at room temperature. Computational results suggest that the effect of borylation on the frontier orbitals of each donor helps to explain differences in the favorability of their condensation reactions with arylboronic acids. The results can inform the use of boronic acids as they are increasingly utilized in the dynamic self-assembly of organic materials and as components in dynamic combinatorial libraries.
- Goldberg, Alexander R.,Northrop, Brian H.
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p. 969 - 980
(2016/02/18)
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- Scalable, Metal- and Additive-Free, Photoinduced Borylation of Haloarenes and Quaternary Arylammonium Salts
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We report herein a simple, metal- and additive-free, photoinduced borylation of haloarenes, including electron-rich fluoroarenes, as well as arylammonium salts directly to boronic acids. This borylation method has a broad scope and functional group tolerance. We show that it can be further extended to boronic esters and carried out on gram scale as well as under flow conditions.
- Mfuh, Adelphe M.,Doyle, John D.,Chhetri, Bhuwan,Arman, Hadi D.,Larionov, Oleg V.
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supporting information
p. 2985 - 2988
(2016/03/19)
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- Efficient metal-free photochemical borylation of aryl halides under batch and continuous-flow conditions
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A rapid, chemoselective and metal-free C-B bond-forming reaction of aryl iodides and bromides in aqueous solution at low temperatures was discovered. This reaction is amenable to batch and continuous-flow conditions and shows exceptional functional group tolerance and broad substrate scope regarding both the aryl halide and the borylating reagent. Initial mechanistic experiments indicated a photolytically generated aryl radical as the key intermediate.
- Chen, Kai,Zhang, Shuai,He, Pei,Li, Pengfei
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p. 3676 - 3680
(2016/06/09)
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- Novel aromatic compounds for organic light-emitting diode and organic light-emitting diode including the same
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The present invention relates to an organic light emitting compound represented by chemical formula A, and to an organic light emitting device comprising the same. In the chemical formula A, a cyclic group A_1 to A_3, R_1 to R_11, L, n, a structural formula Q, and a structural formula Aandprime; are the same as described in the specification.COPYRIGHT KIPO 2016
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Paragraph 0457-0463
(2016/10/09)
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- Transition-metal-free synthesis of phenanthridinones from biaryl-2-oxamic acid under radical conditions
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Na2S2O8-promoted decarboxylative cyclization of biaryl-2-oxamic acid for phenanthridinones has been developed. This work illustrates the first example of intramolecular decarboxylative amidation of unactivated arene under transition-metal-free conditions. Additionally, this approach provides an efficient and economical method to access biologically interesting phenanthridinones, an important structure motif in many natural products. (Chemical Equation Presented).
- Yuan, Ming,Chen, Li,Wang, Junwei,Chen, Shenjie,Wang, Kongchao,Xue, Yongbo,Yao, Guangmin,Luo, Zengwei,Zhang, Yonghui
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supporting information
p. 346 - 349
(2015/02/19)
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- Methanol-promoted borylation of arylamines: A simple and green synthetic method to arylboronic acids and arylboronates
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A Sandmeyer borylation of arylamines via a SN2Ar pathway promoted by methanol with sodium nitrite and hydrochloric acid as diazotization agent has been developed, which provide a simple and green synthetic method to arylboronic acids and arylboronates. Georg Thieme Verlag Stuttgart New York.
- Zhao, Cong-Jun,Xue, Dong,Jia, Zhi-Hui,Wang, Chao,Xiao, Jianliang
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p. 1577 - 1584
(2014/07/08)
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- An easy route to (hetero)arylboronic acids
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An unprecedented spontaneous reactivity between diazonium salts and diboronic acid has been unveiled, leading to a versatile arylboronic acid synthesis directly from (hetero)arylamines. This fast reaction (35 min overall) tolerates a wide range of functional groups and is carried out under very mild conditions. The radical nature of the reaction mechanism has been investigated.
- Erb, William,Hellal, Akila,Albini, Mathieu,Rouden, Jacques,Blanchet, Jerome
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p. 6608 - 6612
(2014/06/09)
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- Sequential one-pot access to molecular diversity through aniline aqueous borylation
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On the basis of our recently reported aniline aqueous borylation, molecular diversity was achieved in a one-pot process by combining other reactions such as esterification, Suzuki-Miyaura coupling, hydrogenolysis, or Petasis borono-Mannich.
- Erb, William,Albini, Mathieu,Rouden, Jacques,Blanchet, Jrme
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p. 10568 - 10580
(2015/01/08)
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- Synthesis of macrocyclic ketones exploiting palladium-catalyzed activation of carboxylic acids as an enabling step
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The novel synthesis of macrocyclic arylketones via palladium-catalyzed cross-coupling of arylboronic acids and carboxylic acids, activated by the treatment with di(N-succinimidyl) carbonate, is disclosed. This allows the high yielding synthesis of various
- Kapdi, Anant R.,Fairlamb, Ian J. S.
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supporting information
p. 961 - 964
(2013/06/27)
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- Mn-catalyzed aromatic C-H alkenylation with terminal alkynes
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The first manganese-catalyzed aromatic C-H alkenylation with terminal alkynes is described. The procedure features an operationally simple catalyst system containing commercially available MnBr(CO)5 and dicyclohexylamine (Cy2NH). The reaction occurs readily in a highly chemo-, regio-, and stereoselective manner delivering anti-Markovnikov E-configured olefins in high yields. Experimental study and DFT calculations reveal that (1) the reaction is initiated by a C-H activation step via the cooperation of manganese and base; (2) manganacycle and alkynylmanganese species are the key reaction intermediates; and (3) the ligand-to-ligand H-transfer and alkynyl-assisted C-H activation are the key steps rendering the reaction catalytic in manganese.
- Zhou, Bingwei,Chen, Hui,Wang, Congyang
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p. 1264 - 1267
(2013/03/14)
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- Nickel-catalyzed borylation of halides and pseudohalides with tetrahydroxydiboron [B2(OH)4]
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Arylboronic acids are gaining increased importance as reagents and target structures in a variety of useful applications. Recently, the palladium-catalyzed synthesis of arylboronic acids employing the atom-economical tetrahydroxydiboron (BBA) reagent has been reported. The high cost associated with palladium, combined with several limitations of both palladium- and copper-catalyzed processes, prompted us to develop an alternative method. Thus, the nickel-catalyzed borylation of aryl and heteroaryl halides and pseudohalides using tetrahydroxydiboron (BBA) has been formulated. The reaction proved to be widely functional group tolerant and applicable to a number of heterocyclic systems. To the best of our knowledge, the examples presented here represent the only effective Ni-catalyzed Miyaura borylations conducted at room temperature.
- Molander, Gary A.,Cavalcanti, Livia N.,Garcia-Garcia, Carolina
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p. 6427 - 6439
(2013/07/26)
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- Enhanced aqueous Suzuki-Miyaura coupling allows site-specific polypeptide 18F-labeling
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The excesses of reagents used in protein chemistry are often incompatible with the reduced or even inverse stoichiometries used for efficient radiolabeling. Analysis and screening of aqueous Pd(0) ligand systems has revealed the importance of a guanidine core and the discovery of 1,1-dimethylguanidine as an enhanced ligand for aqueous Suzuki-Miyaura cross-coupling. This novel Pd catalyst system has now allowed the labeling of small molecules, peptides, and proteins with the fluorine-18 prosthetic [ 18F]4-fluorophenylboronic acid. These findings now enable site-specific protein 18F-labeling under biologically compatible conditions using a metal-triggered reaction.
- Gao, Zhanghua,Gouverneur, Veronique,Davis, Benjamin G.
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supporting information
p. 13612 - 13615
(2013/10/01)
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- Scope of the palladium-catalyzed aryl borylation utilizing bis-boronic acid
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The Suzuki-Miyaura reaction has become one of the more useful tools for synthetic organic chemists. Until recently, there did not exist a direct way to make the most important component in the coupling reaction, namely the boronic acid. Current methods to make boronic acids often employ harsh or wasteful reagents to prepare boronic acid derivatives and require additional steps to afford the desired boronic acid. The scope of the previously reported palladium-catalyzed, direct boronic acid synthesis is unveiled, which includes a wide array of synthetically useful aryl electrophiles. It makes use of the newly available second generation Buchwald XPhos preformed palladium catalyst and bis-boronic acid. For ease of isolation and to preserve the often sensitive C-B bond, all boronic acids were readily converted to their more stable trifluoroborate counterparts.
- Molander, Gary A.,Trice, Sarah L. J.,Kennedy, Steven M.,Dreher, Spencer D.,Tudge, Matthew T.
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supporting information; experimental part
p. 11667 - 11673
(2012/09/05)
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- Palladium-catalyzed borylation of aryl and heteroaryl halides utilizing tetrakis(dimethylamino)diboron: One step greener
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The palladium-catalyzed borylation of aryl and heteroaryl halides with a novel borylating agent, tetrakis(dimethylamino)diboron [(Me2N) 2B-B(NMe2)2], is reported. The method is complementary to the previously reported method utilizing bis-boronic acid (BBA) in that certain substrates perform better under one set of optimized reaction conditions than the other. Because tetrakis(dimethylamino)diboron is the synthetic precursor to both BBA and bis(pinacolato)diboron (B 2Pin2), the new method represents a more atom-economical and efficient approach to current borylation methods.
- Molander, Gary A.,Trice, Sarah L. J.,Kennedy, Steven M.
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supporting information
p. 4814 - 4817,4
(2012/12/12)
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- Organotrifluoroborate hydrolysis: Boronic acid release mechanism and an acid-base paradox in cross-coupling
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The hydrolysis of potassium organotrifluoroborate (RBF3K) reagents to the corresponding boronic acids (RB(OH)2) has been studied in the context of their application in Suzuki-Miyaura coupling. The "slow release" strategy in such SM couplings is only viable if there is an appropriate gearing of the hydrolysis rate of the RBF3K reagent with the rate of catalytic turnover. In such cases, the boronic acid RB(OH)2 does not substantially accumulate, thereby minimizing side reactions such as oxidative homocoupling and protodeboronation. The study reveals that the hydrolysis rates (THF, H2O, Cs2CO 3, 55 °C) depend on a number of variables, resulting in complex solvolytic profiles with some RBF3K reagents. For example, those based on p-F-phenyl, naphthyl, furyl, and benzyl moieties are found to require acid catalysis for efficient hydrolysis. This acid-base paradox assures their slow hydrolysis under basic Suzuki-Miyaura coupling conditions. However, partial phase-splitting of the THF/H2O induced by the Cs2CO 3, resulting in a lower pH in the bulk medium, causes the reaction vessel shape, material, size, and stirring rate to have a profound impact on the hydrolysis profile. In contrast, reagents bearing, for example, isopropyl, β-styryl, and anisyl moieties undergo efficient "direct" hydrolysis, resulting in fast release of the boronic acid while reagents bearing, for example, alkynyl or nitrophenyl moieties, hydrolyze extremely slowly. Analysis of B-F bond lengths (DFT) in the intermediate difluoroborane, or the Swain-Lupton resonance parameter (R) of the R group in RBF3K, allows an a priori evaluation of whether an RBF3K reagent will likely engender "fast", "slow", or "very slow" hydrolysis. An exception to this correlation was found with vinyl-BF 3K, this reagent being sufficiently hydrophilic to partition substantially into the predominantly aqueous minor biphase, where it is rapidly hydrolyzed.
- Lennox, Alastair J. J.,Lloyd-Jones, Guy C.
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supporting information; experimental part
p. 7431 - 7441
(2012/06/16)
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- Solid-state 11B and 13C NMR, IR, and X-ray crystallographic characterization of selected arylboronic acids and their catechol cyclic esters
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Nine arylboronic acids, seven arylboronic catechol cyclic esters, and two trimeric arylboronic anhydrides (boroxines) are investigated using 11B solid-state NMR spectroscopy at three different magnetic field strengths (9.4, 11.7, and 21.1T). Through the analysis of spectra of static and magic-angle spinning samples, the 11B electric field gradient and chemical shift tensors are determined. The effects of relaxation anisotropy and nutation field strength on the 11B NMR line shapes are investigated. Infrared spectroscopy was also used to help identify peaks in the NMR spectra as being due to the anhydride form in some of the arylboronic acid samples. Seven new X-ray crystallographic structures are reported. Calculations of the 11B NMR parameters are performed using cluster model and periodic gauge-including projector-augmented wave (GIPAW) density functional theory (DFT) approaches, and the results are compared with the experimental values. Carbon-13 solid-state NMR experiments and spectral simulations are applied to determine the chemical shifts of the ipso carbons of the samples. One bond indirect 13C-11B spin-spin (J) coupling constants are also measured experimentally and compared with calculated values. The 11B/10B isotope effect on the 13C chemical shift of the ipso carbons of arylboronic acids and their catechol esters, as well as residual dipolar coupling, is discussed. Overall, this combined X-ray, NMR, IR, and computational study provides valuable new insights into the relationship between NMR parameters and the structure of boronic acids and esters. Copyright
- Oh, Se-Woung,Weiss, Joseph W. E.,Kerneghan, Phillip A.,Korobkov, Ilia,Maly, Kenneth E.,Bryce, David L.
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scheme or table
p. 388 - 401
(2012/08/13)
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- A new enabling technology for convenient laboratory scale continuous flow processing at low temperatures
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A new machine for conducting continuous flow processes at low temperatures on a laboratory scale is reported. The use of this cryogenic flow reactor has been demonstrated by the preparation of a variety of (hetero)aromatic boronic acids and esters via lit
- Browne, Duncan L.,Baumann, Marcus,Harji, Bashir H.,Baxendale, Ian R.,Ley, Steven V.
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supporting information; experimental part
p. 3312 - 3315
(2011/09/12)
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- Lithium aminoborohydrides 17. Palladium catalyzed borylation of aryl iodides, bromides, and triflates with diisopropylaminoborane prepared from lithium diisopropylaminoborohydride
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The Alcaraz-Vaultier borylation of aryl halides and triflates is reported utilizing diisopropylaminoborane (BH2N(iPr)2) prepared from the corresponding lithium aminoborohydride (LAB reagent). BH 2N(iPr)2, prepared by reacting lithium diisopropylaminoborohydride with trimethylsilyl chloride, provided the most consistent isolated yields from this reaction. Catalytic amounts of palladium dichloride produced the highest yields from aryl iodides, while catalytic tris(dibenzylideneacetone)dipalladium(chloroform) provided the best yields for aryl bromides and triflates. This route to boronic acids is mild enough to tolerate various functionalities and for the first time employs aryl triflates as substrates for the Alcaraz-Vaultier borylation. In addition, it was found that both boronic acid and ester compounds could be isolated from the reaction mixture utilizing simple work-up procedures. Treatment of the reaction intermediate with an acid/base work-up provided the corresponding boronic acid, while treating the same intermediate with a diol, such as neopentyl glycol, afforded the corresponding boronic ester.
- Haddenham, Dustin,Bailey, Christopher L.,Vu, Chau,Nepomuceno, Gabby,Eagon, Scott,Pasumansky, Lubov,Singaram, Bakthan
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experimental part
p. 576 - 583
(2011/03/18)
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- Distinguishing between pathways for transmetalation in Suzuki-Miyaura reactions
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We report a systematic study of the stoichiometric reactions of isolated arylpalladium hydroxo and halide complexes with arylboronic acids and aryltrihydroxyborates to evaluate the relative rates of the two reaction pathways commonly proposed to account for transmetalation in the Suzuki-Miyaura reaction. On the basis of the relative populations of the palladium and organoboron species generated under conditions common for the catalytic process and the observed rate constants for the stoichiometric reactions between the two classes of reaction components, we conclude that the reaction of a palladium hydroxo complex with boronic acid, not the reaction of a palladium halide complex with trihydroxyborate, accounts for transmetalation in catalytic Suzuki-Miyaura reactions conducted with weak base and aqueous solvent mixtures.
- Carrow, Brad P.,Hartwig, John F.
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supporting information; experimental part
p. 2116 - 2119
(2011/04/23)
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- Preparation and application of SBA-15-supported palladium catalyst for Suzuki reaction in supercritical carbon dioxide
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The external and internal surfaces of SBA-15 were modified by (MeO) 3SiPh and a phosphine ligand, (MeO)3SiCH 2CH2CH2SCH2C6H 4PPh2, before and after the template Pluronic P123 copolymer was removed, respectively. Palladium was then tethered within the cavity of the mesoporous material Ph-SBA-15-PPh3via a ligand-exchange reaction to provide a new supported palladium catalyst Ph-SBA-15-PPh 3-Pd. This catalyst was demonstrated to be a robust and active catalyst in Suzuki reaction of a wide range of aryl bromides with arylboronic acids in supercritical carbon dioxide. After the reaction mixtures were treated at 90 °C for 24 h, the crude coupling products were obtained as crystalline solids when the reaction temperature was lowered to room temperature and the carbon dioxide was then slowly released. The pure products can be obtained by simple recrystallization in good to excellent yields. The Ph-SBA-15-PPh 3-Pd catalyst has low leaching loss and can be reused at least 7 times without loss of activity.
- Feng, Xiujuan,Yan, Mei,Zhang, Tao,Liu, Ying,Bao, Ming
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experimental part
p. 1758 - 1766
(2011/01/12)
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- Thermal and microwave hydrolysis of organotrifluoroborates mediated by alumina
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Hydrolysis of organotrifluoroborates to the corresponding organoboronic acids is readily achieved under either thermal or microwave conditions in the presence of alumina. The organoboronic acid products are obtained in good to excellent yields with essent
- Kabalka, George W.,Coltuclu, Vitali
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experimental part
p. 6271 - 6272
(2010/01/11)
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- Efficient hydrolysis of organotrifluoroborates via silica gel and water
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(Chemical Equation Presented) A general, mild, and efficient method for the hydrolysis of organotrifluoroborates to unveil boronic acids using silica gel and H2O was developed. This method proved to be tolerant of a broad range of aryl-, heteroaryl-, alkenyl-, and alkyltrifluoroborates as well as structurally diverse aminomethylated organotrifluoroborates.As anticipated, electron-rich substrates provided the corresponding boronic acids more readily than electron-poor substrates, owing to the resonance-stabilized difluoroborane intermediate. The method developed was expanded further for the conversion of organotrifluoroborates to the corresponding boronate esters. 2009 American Chemical Society.
- Molander, Gary A.,Cavalcanti, Livia N.,Canturk, Belgin,Pan, Po-Shen,Kennedy, Lauren E.
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supporting information; experimental part
p. 7364 - 7369
(2010/01/16)
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- Palladium-catalyzed cross-coupling of N-benzenesulfonyl-3,4-dibromopyrrole and its application to the total syntheses of lamellarins O, P, Q, and R
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Palladium-catalyzed Suzuki-Miyaura coupling of N-benzenesulfonyl-3,4-dibromopyrrole with a variety of arylboronic acids gave the corresponding 3,4-diarylpyrroles in high yields. The 3,4-differentially arylated pyrroles could also be prepared by stepwise cross-coupling approach. The total syntheses of lamellarins O, P, Q, and R have been achieved by using the cross-coupling and the directed lithiation as key reactions.
- Fukuda, Tsutomu,Sudo, Ei-ichi,Shimokawa, Kozue,Iwao, Masatomo
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p. 328 - 338
(2008/04/01)
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- Adamantyl-substituted retinoid-derived molecules that interact with the orphan nuclear receptor small heterodimer partner: Effects of replacing the 1-adamantyl or hydroxyl group on inhibition of cancer cell growth, induction of cancer cell apoptosis, and inhibition of Src homology 2 domain-containing protein tyrosine phosphatase-2 activity
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(E)-4-[3-(1-Adamantyl)-4′-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC) induces the cell-cycle arrest and apoptosis of leukemia and cancer cells. Studies demonstrated that 3-Cl-AHPC bound to the atypical orphan nuclear receptor small heterodimer partner (SHP). Although missing a DNA-binding domain, SHP heterodimerizes with the ligand-binding domains of other nuclear receptors to repress their abilities to induce or inhibit gene expression. 3-Cl-AHPC analogues having the 1-adamantyl and phenolic hydroxyl pharmacophoric elements replaced with isosteric groups were designed, synthesized, and evaluated for their inhibition of proliferation and induction of human cancer cell apoptosis. Structure-anticancer activity relationship studies indicated the importance of both groups to apoptotic activity. Docking of 3-Cl-AHPC and its analogues to an SHP computational model that was based on the crystal structure of ultraspiracle complexed with 1-stearoyl-2-palmitoylglycero-3-phosphoethanolamine suggested why these 3-Cl-AHPC groups could influence SHP activity. Inhibitory activity against Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp-2) was also assessed. The most active Shp-2 inhibitor was found to be the 3′-(3,3-dimethylbutynyl) analogue of 3-Cl-AHPC.
- Dawson, Marcia I.,Xia, Zebin,Jiang, Tao,Ye, Mao,Fontana, Joseph A.,Farhana, Lulu,Patel, Bhaumik,Li, Ping Xue,Bhuiyan, Mohammad,Pellicciari, Roberto,Macchiarulo, Antonio,Nuti, Roberto,Zhang, Xiao-Kun,Han, Young-Hoon,Tautz, Lutz,Hobbs, Peter D.,Jong, Ling,Waleh, Nahid,Chao, Wan-Ru,Feng, Gen-Sheng,Pang, Yuhong,Su, Ying
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supporting information; experimental part
p. 5650 - 5662
(2009/08/09)
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- Multiple C-H activations to construct biologically active molecules in a process completely free of organohalogen and organometallic components
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(Chemical Equation Presented) Step by step: Highly selective cross dehydrogenase arylation of acetanilides was developed to construct biaryls under mild condition. With this method, different aryl C-H bonds were activated in sequential reactions to construct functionalized carbazoles (see scheme), which are present as key structural units in various biological molecules and organic optical materials.
- Li, Bi-Jie,Tian, Shi-Liang,Fang, Zhao,Shi, Zhang-Jie
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p. 1115 - 1118
(2008/09/21)
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- Asymmetric construction of chiral C-N axes through rhodium-catalyzed 1,4-addition
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Catalytic asymmetric construction of chiral C-N axes has been developed through a rhodium-catalyzed asymmetric 1,4-addition reaction. Both central chirality and axial chirality have been controlled at the same time using Rh/(R,R)-Ph-bod* catalyst with high enantio- and diastereoselectivity. This method has also been applied to the preparation of a planar-chiral ferrocene derivative. The resulting chiral C-N axis can be used as a good template to control the stereochemistry in the subsequent transformations such as alkylation and Diels-Alder reactions.
- Duan, Wei-Liang,Imazaki, Yusuke,Shintani, Ryo,Hayashi, Tamio
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p. 8529 - 8536
(2008/02/09)
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- Deprotection of pinacolyl boronate esters via hydrolysis of intermediate potassium trifluoroborates
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An efficient two-step procedure for the deprotection of pinacolyl organoboronate esters is described. Reaction with excess potassium hydrogen fluoride produces the corresponding stable, crystalline potassium organotrifluoroborate salts. Treatment of the trifluoroborates with either inorganic base or trimethylsilyl chloride and water affords the corresponding organoboronic acid in high yield.
- Yuen, Alexander K.L.,Hutton, Craig A.
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p. 7899 - 7903
(2007/10/03)
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- Synthesis of 4,6-disubstituted pyrimidines via Suzuki and Kumada coupling reaction of 4,6-dichloropyrimidine
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A series of 4,6-disubstituted pyrimidines were synthesized via Suzuki and Kumada coupling reaction of 4,6-dichloropyrimidine.
- Qing, Feng-ling,Wang, Ruowen,Li, Benhan,Zheng, Xing,Meng, Wei-Dong
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- Thrombopoietin mimetics
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Invented are non-peptide TPO mimetics. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected substituted naphthimidazole derivative.
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- Polyfluoroorganoboron-oxygen compounds. 1: Polyfluorinated aryl(dihydroxy)boranes and tri(aryl)boroxins
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A general preparative procedure for polyfluorinated aryl(dihydroxy)boranes C6H5-nFnB(OH)2 (n = 3 - 5) is described. Polyfluorinated aryl(dihydroxy)boranes are easily dehydrated to the corresponding tri(aryl)boroxins (C6H5-nFnBO)3 by thermal or chemical treatment. The property of the acids C6H5-nFnB(OH)2 to condensate depends on the number and on the position of the fluorine atoms in the aryl group. Examples of both classes of boron compounds were isolated as pure individuals and characterized by multinuclear NMR spectroscopy.
- Frohn,Adonin,Bardin,Starichenko
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p. 2827 - 2833
(2008/10/08)
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- Preparation, properties, and synthetic potentials of novel boronates in a fluorous version (fluorous boronates)
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(equation presented) 4a-j R = aryl, alkenyl, alkyl A series of boronic acids were attached to a fluorous tag by esterification. Functional transformations of these boronates together with the fluorous Suzuki coupling reaction illustrated their usefulness in fluorous-phase techniques.
- Chen, Dajun,Qing, Feng-Ling,Huang, Yangen
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p. 1003 - 1005
(2007/10/03)
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- An improved protocol for the preparation of 3-pyridyl- and some arylboronic acids
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3-Pyridylboronic acid was prepared in high yield and bulk quantity from 3-bromopyridine via a protocol of lithium-halogen exchange and "in situ quench". This technique was further studied and evaluated on other aryl halides in the preparation of arylboronic acids.
- Li, Wenjie,Nelson, Dorian P.,Jensen, Mark S.,Hoerrner, R. Scott,Cai, Dongwei,Larsen, Robert D.,Reider, Paul J.
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p. 5394 - 5397
(2007/10/03)
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- (Fluoroorgano)fluoroboranes and -fluoroborates I: Synthesis and spectroscopic characterization of potassium fluoroaryltrifluoroborates and fluoroaryldifluoroboranes
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A convenient preparation of K[ArBF3] (Ar=2-C6H4F, 3-C6H4F, 4-C6H4F, 2,6-C6H3F2, 3,5-C6H3F2, 2,4,6-C6H2F3, 3,4,5-C6H2F3, 2,3,4,5-C6HF4 and C6F5) is offered and the IR and multinuclear NMR spectra of these salts are reported. Treatment of the trifluoroborate salts with BF3 in chlorocarbon solvents provides an easy synthetic route to the corresponding aryldifluoroboranes ArBF2. The multinuclear NMR spectra of ArBF2 are presented. The electron substituent effect of the [-BF3]--group shows this substituent as one of the strongest σ-electron donors, while its π-electron influence is negligible (σI=-0.32, σR=-0.07).
- Frohn,Franke,Fritzen,Bardin
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p. 127 - 135
(2007/10/03)
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- The use of a modified Suzuki reaction for the synthesis of monoarylferrocenes
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A modification of the Suzuki cross-coupling reaction proved to be a clean and useful method for the preparation of monosubstituted arylferrocenes. Iodoferrocene was reacted with a series of substituted arylboronic acids in the presence of sodium carbonate and palladium acetate in aqueous ethanol at room temperature to produce a range of substituted monoarylferrocenes. A systematic investigation undertaken to determine optimal reaction conditions indicated that scrupulous deoxygenation of the solvent is critical. The use of stronger bases such as barium hydroxide and potassium carbonate is favourable and gives rise to better yields of monoarylferrocenes. The reactions also proceed efficiently in aqueous DMF, broadening the scope of the reaction allowing efficient reactions with boronic acids that show low solubility in organic solvents.
- Imrie, Christopher,Loubser, Christa,Engelbrecht, Pieter,McCleland, Cedric W.
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p. 2513 - 2523
(2007/10/03)
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