The free energies of activation for the enantiomerization of the title compounds (Mes2C = X, Mes = 2,4,6-trimethylphenyl) were determined by dynamic NMR to be 4.6, 6.5, and 9.2 kcal mol-1 for X = O, S, and CH2, respectively. Single-crystal X-ray diffraction showed that the structure of dimesitylketone is that of a propeller (C2 symmetry) with the mesityl rings twisted by 50 degrees with respect to the plane of carbonyl. The same structure was predicted by molecular mechanics calculations, which also produced good agreement between computed and experimental barriers for a dynamic process where a disrotatory one-ring flip pathway reverses the helicity of the conformational enantiomers. Solid-state NMR spectra indicated that the enantiomerization barrier in the crystal must be much higher (at least 19 kcal mol-1) than that in solution. Contrary to the case of dimesitylketone, the calculated barrier of dimesitylethylene agrees better with the experimental value if the enantiomerization process is assumed to be a conrotatory two-ring flip pathway.
Static and dynamic stereochemistry of the hydrocarbon comprising a phenyl ring bearing two alpha-naphthyl substituents in the ortho positions, i.e., 1,2-di-(4-methyl-naphth-1-yl)-benzene 1, has been studied by a combination of variable temperature NMR, cryogenic HPLC, and MM calculations. Whereas in solution both syn (meso) and anti (chiral) forms were observed and the corresponding interconversion barrier was determined (Delta G(++) = 19.5 kcal mol(-1)), only the diastereoisomer anti was found to be present in the crystalline state (X-ray diffraction). When the molecule is rendered asymmetric by introduction of a nitro group in the phenyl ring as in 1,2-di-(4-methyl-naphth-1-yl)-4-nitrobenzene 2, the chiral syn and anti diastereoisomers are simultaneously present both in solution and in the solid state, albeit in different proportions. Cryogenic chromatography on a HPLC chiral stationary phase at 20 degrees C allowed the stereolabile diastereoisomers and the corresponding enantiomers to be separated.
General Methods.1 H-NMR spectra were recorded on Varian 400 (400 MHz) spectrometers. Chemical shifts are reported in ppm from TMS with the solvent resonance as the internal standard (deuterochloroform: 7.24 ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, sext = sextet, sept = septet, p = pseudo, b = broad, m = multiplet), coupling constants (Hz). 13 C-NMR spectra were recorded on a Varian 400 (100 MHz) spectrometers with complete proton decoupling. Chemical shifts are reported in ppm from TMS with the solvent as the internal standard (deuterochloroform: 77.0 ppm). Monodimensional NOE experiment (400 MHz, CDCl 3 , 25 °C) was performed by using a DPFGSE-NOE sequence, with a 50 Hz pulse and a mixing time of 1.5 s. Irradiation at the frequency of proton H 1 (5.65 ppm) showed strong positive NOE response of the H 4 frequency, confirming the sin-relationship. Weaker NOE effects were also observed for the equatorial H 2 and the axial H 3 protons. GC-MS spectra were taken by EI ionization at 70 eV on a Hewlett-Packard 5971 with GC injection. They are reported as: m/z (rel. intense). LC-electrospray ionization mass spectra were obtained with Agilent Technologies MSD1100 single-quadrupole mass spectrometer. Chromatographic purification was done with 240-400 mesh silica gel. Other anhydrous solvents were supplied by Sigma Aldrich in Sureseal® bottles and used without any further purification. Commercially available chemicals were purchased from Sigma Aldrich, Stream and TCI and used without any further purification. Melting points were determined with Bibby Stuart Scientific Melting Point Apparatus SMP 3 and are not corrected. Agilent Technologies LC/MSD Trap 1100 series (nebulizer: 15.0 PSI, dry Gas: 5.0 L/min, dry Temperature: 325 °C, capillary voltage positive scan: 4000 mA, capillary voltage negative scan: 3500 mA). Preparation of β-naphthols 1 [1] and N-allenyl amides [2] were accomplished following the reported procedures.
Aryl benzyl oximes having the configuration Z give rise to stereolabile atropisomers when a halogen atom is present in the ortho position of the aryl moiety, as a consequence of the restricted aryl-CN bond rotation. By means of dynamic (1)H NMR spectroscopy it has been possible to determine the corresponding rotation barrier, hence the lifetime of the atropisomers that, in the case of the iodine derivative, was found sufficiently long as to allow a physical separation to be achieved on an appropriately cooled enantioselective HPLC column. Comparison of the barriers determined by dynamic NMR and dynamic HPLC proved the equivalence of the two techniques. When the iodine atom was substituted by an alpha-naphthyl group, two dynamic processes were observed. That with the lower barrier could be determined by NMR and that with the higher barrier by HPLC, thus outlining the complementarity of these two techniques.
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