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. 2017 Jul 12;139(27):9325-9332.
doi: 10.1021/jacs.7b04457. Epub 2017 Jun 27.

CF2H, a Hydrogen Bond Donor

Chanan D Sessler  1 , Martin Rahm  2 , Sabine Becker  1 , Jacob M Goldberg  1 , Fang Wang  1 , Stephen J Lippard  1
Affiliations

CF2H, a Hydrogen Bond Donor

Chanan D Sessler et al. J Am Chem Soc. .

Abstract

The CF2H group, a potential surrogate for the OH group, can act as an unusual hydrogen bond donor, as confirmed by crystallographic, spectroscopic, and computational methods. Here, we demonstrate the bioisosterism of the OH and CF2H groups and the important roles of CF2-H···O hydrogen bonds in influencing intermolecular interactions and conformational preferences. Experimental evidence, corroborated by theory, reveals the distinctive nature of CF2H hydrogen bonding interactions relative to their normal OH hydrogen bonding counterparts.

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Figures

Figure 1.
Figure 1.
(a, b) Crystal structures of 1-OH and I-CF2H; (c, d) IR spectra of 100 mM of 1-OH, p-bromophenol (2-OH), 1-CF2H, and p-bromo-α,α-difluorotoluene (2-CF2H) in CCl4. Red and grey traces in panel (d) correspond to CF2H- and CF2D-containing compounds, respectively. Peaks of interest are identified with arrows. In panel d, the peak labeled with the asterisk appears in the IR spectra of both 1-CF2H and 1-CF2D, suggesting that it cannot be attributed to a CF2–H stretching mode. The O–H stretching of 1-OH is red shifted by −372 cm−1 relative to that of 2-OH. In contrast, the CF2–H stretching of 1-CF2H is blue shifted by +44 cm−1 relative to that of 2-CF2H.
Figure 2.
Figure 2.
Selected conformations/dimers of o-nitrophenol (a; 1-OH) and o-nitro-α,α-difluorotoluene (b; I-CF2H) in the gas phase and calculated relative energies (ΔE). 1H NMR spectroscopic studies showed 1-OH and 1-CF2H to be predominantly monomeric in 100 mM CDCl3 solutions.
Figure 3.
Figure 3.
NMR conformational analysis of 4-NO2 (a), 4-Br (f), and 4-F (k) in CDCl3 at a concentration of 50 mM. Strong (s) and weak (w) NOE interactions observed in 1H-19F HOESY are depicted with solid and dashed double-headed arrows, respectively. Coupling constant analyses of Fb and Fa are shown for each molecule (b-e, g-j, and l-o). Panels l-o are from the 19F{1H} NMR spectrum of 4-F.
Scheme 1.
Scheme 1.
Synthesis of 2,2-difluoro-1-phenyl ethyl triflate derivatives (4-X) from 2,2-difluoro-1-phenyl ethan-1-ol (3-X).
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