Compound 3
1-(cis-3,5-Difluoropiperidin-1-yl)-2,2,2-trifluoroethan-1-one
From: The formation of all-cis-(multi)fluorinated piperidines by a dearomatization–hydrogenation process
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Compound data: 1H NMR
Compound data: 1H{19F} NMR
Compound data: 13C NMR
Compound data: 13C{19F} NMR
Compound data: 19F NMR
Compound data: 19F{1H} NMR
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
Compound 3 was prepared according to the general procedure outlined for compound 1 on 1 mmol scale, 0.5 mol% catalyst, 2 mmol HBpin, 1 M THF at 40 °C, purification with 0-100% CH2Cl2 in pentane. The product was isolated as a white solid (171 mg, 0.79 mmol, 79% (volatile compound, 95% NMR yield), d.r. >99:1). 1H NMR (600 MHz, CDCl3, 299 K) δ 4.85 (dm, J = 34.3 Hz, 1H), 4.77 (dm, J = 34.5 Hz, 1H), 4.53 (ddm, J = 14.3, 10.8 Hz, 1H), 4.12 (ddm, J = 14.9, 9.2 Hz, 1H), 3.51 (ddd, J = 30.6, 14.9, 2.0 Hz, 1H), 3.29 (dd, J = 32.1, 14.3 Hz, 1H), 2.44 (ddddt, J = 15.5, 12.0, 12.0, 2.0, 2.0 Hz, 1H), 2.07 (tdt, J = 36.1, 15.5, 3.5 Hz, 1H); 1H{19F} NMR (600 MHz, CDCl3, 299 K) δ 4.84 (p, J = 3.5 Hz, 1H), 4.81 – 4.76 (m, 1H), 4.53 (ddd, J = 14.3, 3.9, 2.0 Hz, 1H), 4.12 (d, J = 14.9 Hz, 1H), 3.51 (dd, J = 14.9, 2.0 Hz, 1H), 3.28 (d, J = 14.3 Hz, 1H), 2.44 (dtt, J = 15.5, 4.0, 2.0 Hz, 1H), 2.07 (dt, J = 15.5, 3.5 Hz, 1H); 13C NMR (151 MHz, CDCl3, 299 K) δ 157.12 (q, J = 36.4 Hz), 116.34 (q, J = 288.0 Hz), 83.53 (dd, J = 180.5, 1.3 Hz), 83.84 (dd, J = 180.9, 2.9 Hz), 48.67 (d, J = 23.6, 3.4 Hz), 46.47 (d, J = 23.7 Hz), 33.73 (t, J = 21.1 Hz); 13C{sel-19F at -68 and -183 ppm} NMR (151 MHz, CDCl3, 299 K) δ 157.0, 116.1, 83.7, 83.4, 48.5, 46.3, 33.6; 19F NMR (564 MHz, CDCl3, 299 K) δ -68.27 (d, J = 4.0 Hz), -183.21 – -183.87 (m); 19F{1H} NMR (564 MHz, CDCl3, 299 K) δ -68.27 (d, J = 4.1 Hz), -183.51 (d, J = 12.4 Hz), -183.68 (dq, J = 12.4, 4.1 Hz). ESI-MS: calculated [C7H8NOF5 +Na]+: 240.0424, found: 240.0427. IR ν = 2916.5 (w), 2360.9 (w), 1689.7 (s), 1465.9 (m), 1419.6 (w), 1381.1 (w), 1303.9 (w), 1188.2 (s), 1134.2 (s), 1095.6 (s), 1064.7 (s), 972.2 (w), 918.1 (m), 879.6 (m), 848.7 (m), 771.5 (m), 748.4 (w), 671.2 (w), 624.9 (w). M.p: 64-65 °C. In order to prove whether the fluorine atoms are occupying axial or equatorial positions, we conducted a series of NMR studies that includes NOE and HF/FH-HetNOE experiments. All those experiments showed unequivocally that the dominant orientation of the fluorine atoms is axial
