Fluorine in a C−F Bond as the Key to Cage Formation

Holl, Maxwell Gargiulo; Pitts, Cody Ross; Lectka, Thomas

doi:10.1002/anie.201710423

Cited by 23 publications

(18 citation statements)

References 53 publications

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Section: ■ Experimental Sectionmentioning

confidence: 99%

“…1 H and 13 C spectra were acquired on a 400 MHz NMR in CDCl 3 at 25 °C, while 19 F spectra were acquired on a 300 MHz NMR in CDCl 3 . The 1 H, 13 C, and 19 F chemical shifts are given in parts per million (δ) with respect to an internal tetramethylsilane (TMS, δ 0.00 ppm) standard. NMR data are reported in the following format: chemical shifts (multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants [Hz], integration).…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

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Close Amide NH···F Hydrogen Bonding Interactions in 1,8-Disubstituted Naphthalenes

2020

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In this note, we present a series of N-(8-fluoronaphthalen-1-yl)benzamide derivatives designed to maximize amide-NH•••F hydrogen bond interactions therein. A combination of IR and NMR spectroscopy indicates a linear correlation between the high energy shift in NH stretching frequency and the electron withdrawing nature of the substituent, consistent with the trend predicted by DFT calculations. Additionally, a limiting case of hydrogen bonding is observed when the benzamide derivatives are replaced with trifluoroacetamide, causing an additional red shift of 44 cm −1 in the NH stretching frequency. Most importantly, 1 H− 19 F coupling constants in this series are among the largest measured for amide-NH•••F interactions. X-ray crystallography reveals face-to-face alignment of naphthalene rings in these derivatives resulting in part from the NH•••F hydrogen bonds. This motif also dictates the formation of sheets composed of stacked naphthalene rings in the crystal structure as opposed to unfluorinated analogues wherein NH•••OC hydrogen-bonding interactions force benzamide and naphthalene rings to engage in T-shaped π−π interactions instead. Additionally, the NH proton in the trifluoroacetamide derivative engages in extended H-bond interactions in its crystal structure. Note pubs.acs.org/joc

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Section: ■ Experimental Sectionmentioning

confidence: 99%

Close Amide NH···F Hydrogen Bonding Interactions in 1,8-Disubstituted Naphthalenes

2020

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“…Organic fluorine compounds have unique physicochemical properties, generally distinct from their corresponding nonfluorinated analogues, and are the widely used components of medicinal chemistry, agrochemicals, and functional materials. [1][2][3][4][5] Hydrogen bonding is one of the major interactions between pharmaceuticals and their target substrate, indicating that the properties of hydrogen bonding directly correlate with the pharmacological activities. The existence of organofluorine hydrogen bonding has been confirmed by the new criteria of hydrogen-bonding definition.…”

Section: Introductionmentioning

confidence: 99%

“…The influence of carbon hybridization in C─F bond on the ability of F acting as a hydrogen-bonding acceptor has been investigated. Howard [12] studied the interaction of C(sp n )─FÁ Á ÁH─F (n = 1, 2, 3) and found the strength of organofluorine hydrogen bonds decreases in the order: C(sp 3 )─F > C(sp 2 )─F > C(sp)─F. Subsequently, Masoodi et al [7] investigated the effect of carbon hybridization in the interactions of C(sp n )─FÁ Á ÁH─F(n = 1, 2, 3) based on the calculated NMR data.…”

Section: Introductionmentioning

confidence: 99%

“…This conclusion has been further confirmed by Dalvit and coworkers [9] using NMR analysis. They found that the strength of the intermolecular organofluorine hydrogen bonds decreases in the order: -CH 2 F > -CHF 2 > -CF 3 . Recently, we performed a theoretical calculation to investigate the effects of vicinal carbon substituents on intermolecular hydrogen bonds in CH n XCH n FÁ Á ÁH 2 O (n = 0, 1, 2; X = H, F, Cl, Br).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Electronic Structure of Adjacent Carbon on the Strength of C─F⋯H─F Organofluorine Hydrogen Bonds

Jia

Luo

et al. 2019

J Comput Chem

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We investigate the effects of the electronic structure of carbon atom on the organofluorine hydrogen bonds, C─F⋯H─F. Our results show that we can modulate the strength of organofluorine hydrogen bonds by adjusting the volume of fluorine atom in C─F via changing the electronic structure of adjacent carbon atoms. Different with the conventional hydrogen bonds, we found that instead of carbon rehybridization and hyperconjugative effects, the magnitude of fluorine atomic volume plays important roles in determining the strength of the C─F⋯H─F organofluorine hydrogen bonds. The lone pair electrons at both the proximal and the vicinal carbon dramatically reinforce the strength of C─F⋯H─F organofluorine hydrogen bond with its interaction energy in the range of about 15–25 kcal/mol, that is, the carbanion‐mediated organofluorine hydrogen bond could be very strong. Due to the high electronegativity of fluorine atom, it easily attracts the excess electron from the proximal and vicinal carbon, which results in the increase of its volume and negative charge. The enhanced volume of fluorine atom gives rise to the large polarization energy, and its enhanced negative charge favors the large electrostatic interaction, both of which substantially contribute to making the organofluorine hydrogen bonds strong. © 2019 Wiley Periodicals, Inc.

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Enantioselective Electrophilic Aromatic Nitration: A Chiral Auxiliary Approach

et al. 2018

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Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality‐assisted synthesis (CAS). Reported here is an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, and it provides an enantioselective synthesis of a C3v‐symmetric tribenzotriquinacene (TBTQ). These axially‐chiral structures are much sought‐after building blocks for CAS, but they were not accessible prior to this work in enantioenriched form without resolution of enantiomers. This nitration strategy controls the stereochemistry of threefold nitration reactions from above the aromatic rings with chiral diester arms. Dicarbonyl‐to‐arenium chelation rigidifies the reaction systems, so that remote stereocenters position the ester‐directing groups selectively over specific atoms of the TBTQ framework. Closely guided by computational design, a more selective through‐space directing arm was first predicted with density functional theory (DFT), and then confirmed in the laboratory, to outperform the initial structural design. This enantio‐ and regioselective TBTQ synthesis opens a new pathway to access building blocks for CAS.

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Fluorine in a C−F Bond as the Key to Cage Formation

Cited by 23 publications

References 53 publications

Close Amide NH···F Hydrogen Bonding Interactions in 1,8-Disubstituted Naphthalenes

Close Amide NH···F Hydrogen Bonding Interactions in 1,8-Disubstituted Naphthalenes

Effects of Electronic Structure of Adjacent Carbon on the Strength of C─F⋯H─F Organofluorine Hydrogen Bonds

Enantioselective Electrophilic Aromatic Nitration: A Chiral Auxiliary Approach

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