, 8; HRMS (ESI/TOF) m/z
, 39 (1H, dd, J = 1.6, 8.0, arom), 7.45 (1H, td, J = 1.6, 8.0, arom); 13 C NMR (100 MHz, CDCl 3 ) ? 15, 47?2.52 (1H Chiral HPLC: Whelk-O1 (S,S), pp.2-80, 1929.
, ); 13 C NMR (100 MHz, CDCl 3 ) ? 25, 82?7.23?8, vol.84264, issue.8
, arom); 19 F NMR (376.5 MHz) ? ?111.4; 13 C NMR (100 MHz, CDCl 3 ) ? 17, CH 2 ), 2.79?2.837), 118.2 (d, J = 22.5), 123.5, 129.0 (d, J = 9.2), pp.6-99
, 2- chlorocyclopentanone (1 mL, 10 mmol) was added at 0 °C, and the mixture was stirred overnight at rt. The mixture was then diluted with 100 mL of water and extracted with dichloromethane (3 × 40 mL), and the organic layer was dried on MgSO 4 and evaporated under reduced pressure. The crude was purified by flash chromatography (petroleum ether?dichloromethane, 100/0 ? 65/35) to give the desired product: yield 2.5% (75 mg); yellow solid; R f = 0.60 (dichloromethane/petroleum ether); 19 F NMR (376.5 MHz) ? ?61.0; 13 C NMR (150 MHz, CDCl 3 ) ? 25 A solution of n-Butyllithium in hexanes (1.60 M, 0.53 mmol) was added dropwise at ?78 °C (ethanol bath) under nitrogen atmosphere to a solution of 3-(2- bromophenyl) mmol) in anhydrous THF (2.4 mL) Then a solution of chlorodiphenylphosphine for 1o (0.58 mmol), diphenylphosphinic chloride for 1p (0.58 mmol) or 1-cyanobenzimidazole for 1i (2.12 mmol) in anhydrous THF (0.3 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature (cooling bath was not removed) and stirred overnight. The solvent was removed under reduced pressure, and the crude was purified by flash chromatography (petroleum ether?dichloromethane); brown solid, trifluoromethylaniline (1.26 mL, 10 mmol) in DMSO (4 mL) was added sodium hydroxide (0.40 g, 10 mmol) under nitrogen atmosphere. After 15 min of stirring at room temperature The mixture was stirred 60 min at room temperature 137?138 °C; 1 H NMR (400 MHz, CDCl 3 ) ? 2.33?2.50 (4H, m, 2 CH 2 ), 2.76?2.86 (2H1H, br t, J = 7.7, arom), 7.74 (1H, dt, J = 0.5, 7.8, arom) CHCl 3 ). Procedure for Cyano (1i), Diphenylphosphino (1o), and Diphenylphosporyl (1p) Derivatives100) followed by chiral chromatography on Whelk-O1 (S,S) (heptane CDCl 3 ) ? 2.39?2.64 (4H, m, pp.2-76
, Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10
, 13 C NMR spectra for all new compounds
, 1j, 2b, and 2d; 31 P NMR spectra for 1o and 1p. Kinetic experiments and determination of rotational barriers. ?G ? rot values in kJ/mol from models A and B for substituents studied with model 1 (PDF) X-ray data for compound, CIF) ? AUTHOR INFORMATION Corresponding Authors, p.1
, Exploring QSAR: Fundamentals and Applications in Chemistry and Biology, J. Med. Chem, vol.53, issue.123, pp.7843-7851, 1995.
, (27) The results from model B plotted herein are the ?G ? rot at 340K calculated using ?S ? av , the average entropy activation for the whole series (see Table 1 of ref 14). (28) Yilmaz, E. M.; Dogan, I, J. Org. Chem. Tetrahedron: Asymmetry J. E. C, vol.62, issue.19, pp.5208-5210, 1997.
, 2-(N,N-Dimethylamino)aniline was synthesized in two steps from 2-fluoronitrobenzene, which was firstly allowed to react with dimethylamine to generate N,N-dimethyl-2-nitroaniline according to: The subsequent reduction of the nitro group was performed using SnCl 2 as described in the following procedure, Tetrahedron Lett E. M. Tetrahedron: Asymmetry, vol.8030, issue.15, pp.6366-6369, 1984.
, (32) (a) Reichardt, C.; Welton, T. Solvent and Solvent Effects in Organic Chemistry, 512?518. (33) See the Supporting Information (34) Wolf, C. Dynamic Stereochemistry of Chiral Compounds: Principles and Applications, pp.3635-3639, 1973.