19F‐NMR Diastereotopic Signals in Two N-CHF2 Derivatives of (4S,7R)-7,8,8-Trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole

Abstract

In this paper, we report the anisochrony of the fluorine atoms of a CHF2 group when linked to a pyrazole ring. The pyrazole is part of (4S,7R)-7,8,8-trimethyl-4,5,6,7-tetrahydro-4,7-methano-2H-indazole also known as (4S,7R)-campho[2,3-c]pyrazole, which has two stereogenic centers. Gauge-Independent Atomic Orbital (GIAO)/Becke, 3-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,f) calculated 19F chemical shifts of the minimum energy conformations satisfactorily agree with the experimental data. The energy differences between minima need to consider solvent effects (continuum model) to be satisfactorily reproduced.

Tuning the Biological Activity of PI3Kδ Inhibitor by the Introduction of a Fluorine Atom Using the Computational Workflow

“…Coupling constants (J) are expressed in Hertz. A JEOL Royal HFX probe head was used for recording the 13 C NMR spectrum as it allows measurements to be taken with the simultaneous decoupling of both 1 H and 19 F nuclei [24]. Atmospheric pressure ionization and electrospray ionization mass spectra were obtained using an Agilent 6130 LC/MSD spectrometer or Agilent 1290 UHPLC system coupled with an Agilent QTOF 6545 mass spectrometer.…”

Assignment of 1H and 13C NMR data for three pairs of diastereomers of 4′‐X benzo[1,3]cyclopropa[1,2‐b]chromene‐4,5‐diones (X = H, OCH3, and Cl)

“…We have been using gauge‐independent atomic orbital (GIAO)/B3LYP/6‐311++G(d,p) calculated chemical shifts since 1998 . Several kinds of problems were studied using both chemical shifts, δ , and differences between chemical shifts, Δ δ : chiral cyclohexanone derivatives, isomerism, substituent effects, conformational analysis, interpolation between fast interconverting conformers and rotamers, diastereotopic 15 N and 19 F signals, among other topics.…”