Partially Bridge-Fluorinated Dimethyl Bicyclo[1.1.1]pentane-1,3-dicarboxylates:  Preparation and NMR Spectra

Shtarev, Alexander B.; Pinkhassik, Evgueni; Levin, Michael D; Stibor, Ivan; Michl, Josef

doi:10.1021/ja0000495

Cited by 42 publications

(49 citation statements)

References 22 publications

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“…This trend contrasts with that of substituent effects on 2,3 J(F,F) couplings which can be dominated by non-contact contributions. 17,18 With only one exception, i.e.…”

Section: Resultsmentioning

confidence: 99%

Substituent effects on scalar J(¹³C, ¹³C) couplings in pyrimidines. An experimental and DFT study

Kowalewski¹,

Esteban²,

Barone³

et al. 2004

Magnetic Reson in Chemistry

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One- two- and three 13C, 13C (n = 1, 2, 3) scalar couplings, (n)J(C,C) in a set of pyrimidine derivatives were studied both experimentally at natural abundance and theoretically by their DFT calculation of all four contributions. Trends of non-contact terms are discussed and substituent effects are rationalized, comparing some of them with the corresponding values in benzene and pyridine. Although substituent effects on non-contact terms are relatively important, the whole trend is dominated by the Fermi contact term. According to the current literature, substituent effects on 1J(C,C) couplings in benzene derivatives are dominated by the inductive effect, which, apparently, is also the case in nitrogen heteroaromatic compounds. However, some differences observed in this work for substituent effects on 1J(C,C) couplings in pyrimidine derivatives suggest that in the latter type of compounds substituent effects can be affected by the orientation of the ring nitrogen lone pairs.

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“…This trend contrasts with that of substituent effects on 2,3 J(F,F) couplings which can be dominated by non-contact contributions. 17,18 With only one exception, i.e.…”

Section: Resultsmentioning

confidence: 99%

Substituent effects on scalar J(¹³C, ¹³C) couplings in pyrimidines. An experimental and DFT study

Kowalewski¹,

Esteban²,

Barone³

et al. 2004

Magnetic Reson in Chemistry

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“…2 Sodium cyanide (0.220 g, 4.4 mmol) was added to a round bottom flask with a magnetic stir bar and dried overnight at 120 C at 60 mTorr. After cooling to room temperature, anhydrous DMSO (5 mL) and 1,3-diiodobicyclo[1.1.1]pentane 3,4 (700 mg, 2.2 mmol) were added. The flask was connected to a cooling trap kept at -20 o C followed by a Schlenk flask cooled by liquid nitrogen to condense the [1.1.1]propellane produced.…”

Section: Closo-1-(3-iodobicyclo[111]pent-1-yl)-112-dicarbadodecabomentioning

confidence: 99%

High-Band-Gap Polycrystalline Monolayers of a 12-Vertex p-Carborane on Au(111)

Wrochem¹,

Scholz²,

Gao³

et al. 2010

J. Phys. Chem. Lett.

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Experimental manipulations were carried out using standard vacuum and inert atmosphere techniques. All chemicals were obtained from Sigma-Aldrich and used as received. closo-1,12-Dicarbadodecaborane was purchased from Katchem Ltd., E. Krásnohorské 6, 110 00 Prague 1, Czech Republic. Diethyl ether and THF were dried over Na metal and NaK, respectively, and distilled fresh prior to use. Deuterated solvents were obtained from Cambridge Isotopes Laboratories and used as received. NMR spectra were recorded either on a Varian INOVA 500 spectrometer at 500 MHz or a Bruker Avance-III 300 spectrometer at 300 MHz. Chemical shifts are given in ppm with positive shifts downfield: all 1 H and 13 C chemical shifts were referenced relative to internal residual protons from a lock solvent. For 11 B decoupled 1 H NMR spectra, the decoupling was not complete and BH proton peaks did not integrate to expected values. The values listed are the actual values observed and the expected values are in brackets. IR spectra were recorded eith a Nicolet Nexus 670 FT-IR spectrophotometer either in KBr pellets or neat compound deposited onto a Ge window. Mass spectra were recorded using a Thermo Finnigan Polaris Q GC/MS instrument using a Phenomenex ZB-5ms general purpose column (30 m, 0.25 mm ID, 0.25 um film thickness, max. 320 ºC isotherm/340 ºC program) in electron impact (70 eV) ionization mode. Elemental analysis was performed by Columbia Analytical Services, 3860 S. Palo Verde Road, Suite 302, Tucson, AZ 85714. closo-1-Iodo-1,12-dicarbadodecaborane 1. The synthesis of 1 was adapted from a literature procedure. 1 To a flame-dried round bottom flask were added p-carborane (0.2 g, 1.39 mmol) and anhydrous diethyl ether (5 mL). The solution was stirred at room temperature under nitrogen while n-BuLi (1.6 M, 1.6 mmol, 1.0 mL) was added dropwise from a syringe. The reactants were stirred for

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“…Bridge-Fluorinated Derivatives Bridge-fluorinated BCP derivatives have garnered significant interest in the past two years.U nsurprisingly,d irect fluorination of 1,3-disubstituted BCPs with limited gaseous F 2 is extremely unselective,p roducing 14 out of the 15 possible bridge-fluorinated derivatives. [48] Exhaustive fluorination gives access to penta-and hexafluorinated derivatives in synthetically useful yields. [25b] Recent attempts [31a] at con-trolled fluorination on the BCP core through the electrochemical method of Baran, [49] and the amine-directed, Pdcatalysed approaches of Xu [50] and Hrdina, [51] have all proven unsuccessful.…”

Section: Bridge-chlorinated Derivativesmentioning

confidence: 99%

Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives

et al. 2021

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Escaping from flatland", by increasing the saturation level and three-dimensionality of drug-like compounds, can enhance their potency, selectivity and pharmacokinetic profile. One approach that has attracted considerable recent attention is the bioisosteric replacement of aromatic rings, internal alkynes and tert-butyl groups with bicyclo[1.1.1]pentane (BCP) units. While functionalisation of the tertiary bridgehead positions of BCP derivatives is well-documented, functionalisation of the three concyclic secondary bridge positions remains an emerging field. The unique properties of the BCP core present considerable synthetic challenges to the development of such transformations. However, the bridge positions provide novel vectors for drug discovery and applications in materials science, providing entry to novel chemical and intellectual property space. This review aims to consolidate the major advances in the field, serving as a useful reference to guide further work that is expected in the coming years. Joseph Anderson completed his MChem in 2020 (University of Oxford, Prof. Timothy Donohoe) working on cobalt-catalysed transformations of boronic acids. He subsequently joined the GSK/University of Strathclyde Collaborative Industrial PhD Programme, where he is currently working under the supervision of Dr Darren Poole, Dr Nicholas Measom and Prof. John Murphy on bicyclo[1.1.1]pentane methodology. Nicholas Measom completed his PhD in 2017 (GSK/University of Strathclyde Collaborative Industrial PhD programme, Dr David Hirst and Dr Craig Jamieson) working on the synthesis and application of bicyclo[1.1.1]pentanes within Lp-PLA2 inhibitors. He joined GSK as a synthetic medicinal chemist in 2017 and became an Investigator in 2020. Darren Poole completed his DPhil in 2014 (University of Oxford, Prof. Timothy Donohoe) where he worked on nucleophilic dearomatisation reactions, and hydrogen borrowing reactions of methanol. He joined GSK's Flexible Discovery Unit as a synthetic chemist in 2014, and is now a Scientific Leader and GSK Fellow in the Medicinal Chemistry department. His research interests are particularly focussed on the application of new synthetic methodologies and technologies in drug discovery. John Murphy was born in Dublin and educated at the University of Dublin (TCD) and the University of Cambridge. After Fellowships at Alberta and Oxford, he was appointed as Lecturer, then Reader, at the University of Nottingham. Since 1995, he has held the Merck-Pauson Professorship at the University of Strathclyde. His interests are in mechanism and synthesis.

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Partially Bridge-Fluorinated Dimethyl Bicyclo[1.1.1]pentane-1,3-dicarboxylates: Preparation and NMR Spectra

Cited by 42 publications

References 22 publications

Substituent effects on scalar J(¹³C, ¹³C) couplings in pyrimidines. An experimental and DFT study

Substituent effects on scalar J(¹³C, ¹³C) couplings in pyrimidines. An experimental and DFT study

High-Band-Gap Polycrystalline Monolayers of a 12-Vertex p-Carborane on Au(111)

Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives

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Partially Bridge-Fluorinated Dimethyl Bicyclo[1.1.1]pentane-1,3-dicarboxylates: Preparation and NMR Spectra

Cited by 42 publications

References 22 publications

Substituent effects on scalar J(13C, 13C) couplings in pyrimidines. An experimental and DFT study

Substituent effects on scalar J(13C, 13C) couplings in pyrimidines. An experimental and DFT study

High-Band-Gap Polycrystalline Monolayers of a 12-Vertex p-Carborane on Au(111)

Bridge Functionalisation of Bicyclo[1.1.1]pentane Derivatives

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Substituent effects on scalar J(¹³C, ¹³C) couplings in pyrimidines. An experimental and DFT study

Substituent effects on scalar J(¹³C, ¹³C) couplings in pyrimidines. An experimental and DFT study