20 article(s) from O'Hagan, David
Graphical Abstract
Figure 1: Examples of liquid crystal candidates with negative values for dielectric anisotropy (Δε) [6-10].
Figure 2: Synthetic candidate LC targets 8–11.
Scheme 1: Synthesis of 8. Reagents and conditions: a) TMSCF3, NaI, THF, reflux, 55% [13,14].
Scheme 2: Synthesis of 9. Reagents and conditions: a) NBS, HF·Py, DCM; b) t-BuOK, DCM, 42% in two steps [15]; c) ...
Scheme 3: Synthesis of compound 10. Reagents and conditions: a) NaBH4, MeOH, rt, 45%; b) C4H9OCH=CH2, Pd(TFA)2...
Scheme 4: Synthesis of compounds 11. Reagents and conditions: a) PPh3CH3Br, t-BuOK, diethyl ether, 0 °C to rt...
Figure 3: Theory study exploring the relative energies for different conformers of 11a.
Graphical Abstract
Figure 1: Structures of trifluoromethyl sulfonyl ether bioactives.
Figure 2: Comparison of log P values of comparative aryl thioether motifs [18].
Figure 3: α,α-Difluoroethyl thioether substrates for metabolism studies.
Scheme 1: Fluorometabolites 6–8 isolated after incubation of 4 with C. elegans. Ratios are the average of thr...
Scheme 2: Putative pathways for (α,α-difluoroethyl)(4-methoxyphenyl)sulfane (4) metabolism.
Scheme 3: C. elegans incubation of 5. Ratios are the average of three incubations.
Scheme 4: Incubation (four times) of oxygen ether 14 with C. elegans, gave 4-acetoxyphenol (15) as the major ...
Graphical Abstract
Figure 1: C–F activation of benzylic fluorides to generate benzylamine or diarylmethane products.
Figure 2: 7-[2H1]-(R)-Benzyl fluoride ((R)-1).
Scheme 1: Synthesis of enantioenriched 7-[2H1]-(R)-benzyl fluoride ((R)-1) from benzaldehyde (2).
Figure 3: Partial 2H{1H} NMR (107.5 MHz) with PBLG in CHCl3 (13% w/w). (A) racemic sample of 6 (from Table 1, entry ...
Scheme 2: Synthesis of enantioenriched (S)-diarylmethane 10 from diaryl ketone 11 and confirmation of configu...
Figure 4: Possible reactive intermediates for C–F activation of benzyl fluoride 1 with strong hydrogen bond d...
Graphical Abstract
Figure 1: The derivatives of all-cis-2,3,5,6-tetrafluorocyclohexane.
Scheme 1: Reagents and conditions: a) Li (2.5 equiv), NH3, t-BuOH (1 equiv), MeI (2 equiv), 3 h, −78 °C, 18 h...
Scheme 2: Reagents and conditions: a) Et3N·3HF (8 equiv), 18 h, 140 °C; b) Tf2O (4 equiv), pyridine, 1 h, 0 °...
Scheme 3: Reagents and conditions: a) Et3N·3HF (8 equiv), 18 h, 140 °C; b) Tf2O (4 equiv), pyridine, 1 h, 0 °...
Scheme 4: Reagents and conditions: a) terephthaloyl chloride (1 equiv), Et3N (4 equiv), DMAP (20 mol %), DCM,...
Figure 2: X-ray structures and crystal packing of compounds 13, 14 and 15.
Graphical Abstract
Figure 1: Selected fluorinated polar alicyclic scaffolds.
Scheme 1: Retrosynthetic plan to the preparation of 1,1,3,3-tetrafluorocyclohexane structures.
Scheme 2: Preparation of starting materials 5c and 6a–c.
Scheme 3: Deoxofluorination of diketones 5. Reagents and conditions: a) DAST, DCM, rt, overnight, 4a (traces)...
Scheme 4: Fluorodesulfurisation of bis-dithianes 6. Reagents and conditions: a) NIS, HF·Py, DCM, −78 °C to rt...
Figure 2: X-ray structure of compound 4c. The image shows two molecules stacked with the non-fluorine face po...
Figure 3: 1H NMR spectra of 4c. A) shows the spectrum in [2H8]-toluene, and B) shows the spectrum in chlorofo...
Figure 4: Electrostatic potential map for 4c calculated at the B3LYP/6-311G(d,p) level for an optimised struc...
Graphical Abstract
Figure 1: All cis-hexafluoro- 1 and tetrafluorocyclohexanes 2 and 3 result in facially polarised ring motifs ...
Scheme 1: Preparation of benzoic acids 11–13; i. HIO4·2H2O (50%), AcOH, H2SO4, I2, H2O, 70 °C 24 h, 92%.; ii....
Scheme 2: Synthesis of benzaldehyde derivatives 14 and 15: i. Pd(PPh3)4, Bu3SnH, THF, CO (1 atm), 50 °C, 2–3 ...
Figure 2: X-ray structure of aldehyde 15. CCDC number 1432193.
Scheme 3: Olefination reactions of 15 and the X-ray structure of 17 (CCDC number 1432194): i. Zn, TiCl4, THF,...
Scheme 4: Reactions from aldehyde 15: i. NaBH4, THF, 20 °C, 1 h, 98%.; ii. HI (57%), CHCl3, 30 h, 95%; iii. Bu...
Scheme 5: Reactions of benzyl azide 21; i. 24, Cu(OAc)2, Na ascorbate, t-BuOH, H2O, 20 °C, 16 h, 72%; ii. HCl...
Scheme 6: Reactions of aldehyde 14: i. NaBH4, THF, rt, 1 h, 98%.; ii. HI (57%), CHCl3, 30 h, 94%; iii. Bu4NN3...
Graphical Abstract
Figure 1: Some spacial and electronic mimetics with fluorine as a design feature [3-6].
Figure 2: α-Fluorovinyl thioesters offer prospects as thioester enol/ate mimetics [7].
Scheme 1: HF·Py mediated hydrofluorinations of 1a.
Scheme 2: BF3·Et2O/3HF·Et3N mediated hydrofluorination of 1a.
Scheme 3: Proposed Lewis acid-mediated hydroflurination of sulfides 1.
Graphical Abstract
Figure 1: General strategies for incorporating functional groups (FGs) on the surface of self-assembled monol...
Figure 2: XPS scans after reactions with a) :CBr2; b) :CCl2 and c) :CF2. In each case the upper traces are sc...
Scheme 1: Model reactions of dec-1-ene (1) with dihalocarbenes in the liquid phase. a) and b) NaOH, BTEAC, CHX...
Figure 3: AFM images of 5 μm × 5 μm area of C11-vinyl SAMs modified with a) :CBr2 carbene, RMS 93 pm; b) :CCl2...
Figure 4: The experimental set-up for the dibromo-, dichloro- and difluorocarbene reactions performed on C11-...
Graphical Abstract
Figure 1: The CF2 group in 1c accelerates RCM reactions relative to CHF (1d) and CH2 (1e) and with a similar ...
Figure 2: X-ray structures of a) 1,1,4,4- (3) b) 1,1,7,7- (4) and c) 1,1,6,6- (5) tetrafluorocyclododecanes. ...
Figure 3: Synthesis targets: Palmitic acid analogues 6a–c.
Scheme 1: Synthesis route to 8,8-difluorohexadecanoic acid (6a).
Scheme 2: The synthesis of palmitic acid analogues 6b and 6c.
Figure 4: DSC traces for the three palmitic acid analogues 6a–c.
Figure 5: The X-ray crystal structures of 8,8-difluorohexadecanoic acid (6a).
Figure 6: The X-ray structure of 8,8,11,11-tetrafluorohexadecanoic acid (6c).
Scheme 3: Synthesis route to the tetrafluorinated alkane 27.
Figure 7: The X-ray structure of 8,8,11,11-tetrafluorononadecane (27).
Figure 8: Conformational interconversion of 1,4-di-CF2 motif.
Graphical Abstract
Figure 1: The Dunitz and Shearer structure of cyclododecane (1) [1,2]. There are four endo hydrogens above and fou...
Figure 2: Crystal structures of (a) 1,1,4,4- (b) 1,1,7,7- and (c) 1,1,6,6-tetrafluorocyclododecanes (2–4) , i...
Figure 3: Erythro- and threo-1,2-difluorocyclododecanes (5a and 5b).
Scheme 1: Synthetic routes to erythro- (5a) and threo-1,2-difluorocyclododecane (5b).
Figure 4: X-ray crystal structure of threo-1,2-difluorocyclododecane (5b) showing corner angles and represent...
Figure 5: Variable-temperature 19F{1H} NMR of erythro- (5a) and threo-1,2-difluorocyclododecane (5b).
Figure 6: Calculated relative energies of the conformations of the erythro (5a) and threo (5b) stereoisomers ...
Graphical Abstract
Figure 1: Enantiomers of α-(trifluoromethyl)-β-lactam (1).
Scheme 1: Synthetic route involving a diastereoisomeric separation to α-(trifluoromethyl)-β-lactam ((S)-1) fr...
Figure 2: X-ray structures of (a) β-lactam (S)-1 and (b) (αR,3R)-5c. (a) Determination of the absolute stereo...
Scheme 2: Synthesis of stereoisomers 5c. The stereochemistry of the major isomer (αR,3R)-5c was solved by X-r...
Graphical Abstract
Scheme 1: The C–F bond forming Prins reaction leading to 4-fluoropyrans [10].
Figure 1: X-ray crystal structure of syn-5a.
Scheme 2: Ring opening hydrogenation of an oxa-Prins product.
Figure 2: X-ray crystal structure of the major bicyclic tetrahydropyran diastereoisomer 9b.
Scheme 3: Reaction using (E)-11a and (Z)-11b hex-3-en-1-ols with 4-nitrobenzaldehyde to generate 4-fluorotetr...
Figure 3: X-ray crystal structure of the minor anti-piperidine product 14d.
Graphical Abstract
Scheme 1: Previous six step route to the vicinal all-syn-trifluoro motif.
Scheme 2: Novel three step successive fluorination strategy from α,β-epoxy alcohols to different diastereoiso...
Scheme 3: Synthesis approach to the requisite α,β-epoxy alcohols 6b and 7b.
Figure 1: X-ray structure (CCDC 750307) and stereochemistry of α,β-epoxy alcohol 7b.
Figure 2: X-ray structure (CCDC 750306) and stereochemistry of α,β-epoxy alcohol 7a.
Scheme 4: Three step sequential fluorination from α,β-epoxy alcohols to eg. the vicinyltrifluoro tosylate 11.
Scheme 5: Unexpected cyclisation of 9b to furan 14 with HF·pyridine. An X-ray structure of 14 (CCDC 750309) r...
Scheme 6: Epoxide ring opening of 9b with 3HF·Et3N required forcing conditions. The structure and stereochemi...
Scheme 7: Three step sequential fluorination from α,β-epoxy alcohol 7b to vicinal trifluoro tosylate 17b.
Scheme 8: Epoxide ring opening with 3HF∙Et3N and synthesis of the all-syn vicinal trifluoro tosylate 17a.
Graphical Abstract
Scheme 1: Biosynthetic pathway from fluoride ion to fluoroacetate 1 and 4-fluorothreonine 2 in S. cattleya [2].
Figure 1: Synthesized phosphonates 8 and 9 and cyclic phostones 10 and 11.
Scheme 2: Synthetic route A. Reagents and conditions: a) acetone, concd H2SO4 (cat.), 6 h, 86%; b) Deoxo-fluo...
Scheme 3: Synthetic route B. Reagents and conditions: a) acetone, concd H2SO4 (cat.), 4 h, 90%; b) TrCl, pyri...
Figure 2: X-Ray crystal structure of cyclohexylammonium salt 8a.
Graphical Abstract
Scheme 1: Synthesis of vicinal dimethyl difluorosuccinates. The conversion of the tartrates 1 with SF4 and HF ...
Scheme 2: Schlosser's route to vicinal erythro- or threo- difluoro alkanes 5 [13].
Scheme 3: Halofluorination of electron-rich alkenes with in situ fluoride displacement generates vicinal difl...
Scheme 4: Bromofluorination of stilbene [19].
Scheme 5: Treatment of anti-14 with base generated the E-fluorostilbene 15 by an anti elimination mechanism.
Scheme 6: Hypothesis for the predominent retention of configuration during fluoride substitution via phenoniu...
Scheme 7: Proposed C-C bond rotation during the preparation of 14 from cis-stilbene.
Figure 1: Crystal structure of erythro-13.
Figure 2: X-ray structure of threo-13.
Figure 3: Expanded regions of the second order AA'XX' spin systems in the 1H-NMR (left) and 19F-NMR spectra (...
Figure 4: NMR coupling constants and calculated relative energies (kcalmol-1) of the staggered conformers of ...
Scheme 8: Synthesis of erythro-19 via ozonolysis of erythro-13.
Figure 5: X-ray structure of erythro-19.
Figure 6: X-ray structure of threo-19.
Scheme 9: Strategy for the preparation of diastereoisomers of erythro- and threo- 20.
Figure 7: NMR (CDCl3, RT) coupling constants of erythro- and threo- 2,3-difluoro-3-phenylpropionates 21.
Figure 8: Newman projections showing the staggered conformations of erythro- and threo- 21.
Figure 9: X-ray structure of methyl threo- 21.
Figure 10: The preferred conformation of α-fluoroamides has the C-F and amide carbonyl anti-planar [29,30].
Scheme 10: The synthesis of stereoisomers of erythro- and threo- 22. These isomers could be separated by chrom...
Figure 11: X-ray structure of erythro-22.
Figure 12: Crystal packing of erythro-22 clearly indicating intermolecular hydrogen bonding.
Figure 13: X-ray structure of threo-22.
Figure 14: The conformations of erythro- and threo- 23 are very different as a consequence of each conformatio...
Figure 15: 3JHF and 3JHH coupling constants for the erythro (yellow) and threo (blue) diastereoisomers of the ...
Figure 16: Newman projections of the three staggered conformations of the erythro and threo stereoisomers of t...
Figure 17: The average coupling constant with no conformational bias. The limiting coupling constants Jg = 8 H...
Figure 18: The observed 3JHF coupling constants are an average over the rotational isomers.
Graphical Abstract
Scheme 1: Reagents: i N3CH2C(O)F, AlMe3
Scheme 2: Reagents: i KF, DMF, 73%; ii NaOH, EtOH then aqHCl, 44%; iii (CO)2Cl2, 90%.
Scheme 3: Reagents: i iPr2EtN, Yb(OTf)3, 9, DCM, 92%; ii I2, THF/ H2O, Na2S2O3, 82%.
Scheme 4: Reagents i. I2, THF/H2O.
Scheme 5: Reagents: (a) I2, THF/H2O, Na2S2O3.
Scheme 6: Reagents: i iPr2EtN, Yb(OTf)3, 9 or PhCHFCOCl, DCM, 92%.
Scheme 7: Reagents: i. LiAlH4, THF, 99%; ii. HCl-Et2O.
Figure 1: ORTEP drawing of (2S, 2'S)-28 showing two crystallographically independent molecules within the uni...
Scheme 8: Reagents: (a) I2, THF/H2O, Na2S2O3.