N. Marquet et al. / Tetrahedron 64 (2008) 75e83
81
4.2.12. 4-(1-Benzylpiperidin-4-ylimino)-1,1,1-trifluoro-2-
(trifluoromethyl)pentan-2-ol (2i)
NMR (182 MHz, CDCl3): d ꢀ78.9 (s, 12F). Anal. Calcd for
C14H16F12N2O2: C, 35.60; H, 3.41. Found: C, 36.44; H, 3.89.
This compound was prepared by following the same proce-
dure as that described above for 2a, starting from 1a (4.35 g,
19.4 mmol) and 4-amino-1-benzylpiperidine (3.14 mL,
16.2 mmol), reacting at 70 ꢁC for 70 h in the presence of
InBr3 (13.6 mg, 2.0 mol %). Recrystallization of the crude
product from pentane gave 2i as a pale yellow solid (3.92 g,
61%). Mp¼126e128 ꢁC. 1H NMR (200 MHz, CDCl3):
d 1.64 (m, 4H, 2CH2 piperidine), 1.92 (s, 3H, CH3), 2.12 (m,
2H, CH2 piperidine), 2.61 (s, 2H, CH2), 2.73 (m, 2H, CH2
piperidine), 3.40 (m, 1H, CH of piperidine), 3.46 (s, 2H,
CH2ePh), 7.25 (m, 5H, arom.). 19F NMR (188 MHz, CDCl3):
d ꢀ78.57 (s, 6F). 13C NMR (75 MHz, CDCl3): d 20.47 (s, C,
CH3), 32.42 (s, C, CH2ePh), 51.77 (s, C, CH2), 31.35, 33.76,
56.59, 63.57 (s, 5C piperidine), 126.39 (s, 1C, p-CH),
127.43 (s, 1C, m-CH), 128.62 (s, 2C, m-CH), 129.50 (s, 2C,
o-CH), 138.81 (s, 1C, p-CH), 167.82 (s, C, C]N). Reso-
nances for CF3 groups were not observed due to a too short re-
laxation period or a non-adapted pulse angle. Anal. Calcd for
C19H25F6N2O: C, 55.47; H, 6.12. Found: C, 55.83; H, 6.58.
4.2.15. Racemic trans-4,40-(cyclohexane-1,2-diylbis(azan-1-
yl-1-ylidene))bis(1,1,1-trifluoro-2-(trifluoromethyl)pentan-
2-ol) (rac-3b)
Compound rac-3b was prepared as described for 2d starting
from 1c (2.50 g, 11.1 mmol), trans-1,2-diaminocyclohexane
(0.63 g, 5.5 mmol), and montmorillonite (0.80 g) to give rac-
1
3b as a white solid (3.97 g, 68%). Mp¼108.4 ꢁC. H NMR
(500 MHz, CDCl3): d 1.38e1.84 (m, 8H, cyclohexyl), 2.01 (s,
6H, Me), 2.65 (m, 2H, CHeN of cyclohexyl), 10.19 (s, 2H,
OH). 13C NMR (75 MHz, CDCl3): d 170.0 (2C, CN), 21.10
(2C, CH2eCeCF3), 24.20 (2C, CH3), 32.02 (2C, CH2 cyclo-
hexyl), 39.10 (2C, CH2eCN cyclohexyl), 64.30 (2C, CHeN
cyclohexyl), 122.0 (2C, CO), 126.0 (q, 2C). 19F NMR
(182 MHz, CDCl3): d ꢀ78.72 (q, J¼10.35, 6F), ꢀ79.20 (q,
J¼10.34, 6F). HRMS (70 eV, EI): m/z calcd for
C18H22F12N2O2: 526.1490; found: 526.1521 (6 ppm).
[MꢀCF3]þ (C17H22N2O2F9) calcd: 457.1538; found: 457.1568.
4.2.16. 4,40-((1R,2R)-Cyclohexane-1,2-diylbis(azan-1-yl-1-
ylidene))bis(1,1,1-trifluoro-2-(trifluoromethyl)pentan-2-ol)
((R,R)-3c)
4.2.13. 4-(1-Benzylpiperidin-4-ylimino)-4-phenyl-1,1,1-
trifluoro-2-(trifluoromethyl)butan-2-ol (2j)
This compound was prepared by following the same proce-
dure as that described above for 2f, starting from 1b (2.40 g,
8.4 mmol) and 1,3-phenylenedimethanamine (0.42 mL,
3.2 mmol) in benzene (15 mL), in the presence of La(OTf)3
(90 mg, 0.15 mmol, 1.8 mol %), reacting for 3 days in a Soxh-
Compound (R,R)-3c was prepared in a similar manner as
that described above for rac-3b, starting from 1a (4.24 g,
19.0 mmol), (1R,2R)-diaminocyclohexane (0.63 g, 5.5 mmol),
and montmorillonite (1.20 g), to give (R,R)-3c (6.97 g, 70%)
as a white solid. [a]2D0 ꢀ32 (c 0.01, CH2Cl2). 1H NMR
(200 MHz, CDCl3): d 1.42e1.85 (m, 8H, cyclohexyl), 2.02
(s, 6H, 2Me), 2.66 (s, 4H, cyclohexyl), 3.57 (m, 2H, CHe
N), 10.19 (s, 2H, OH). 13C NMR (75 MHz, CDCl3): d 170.0
(2C, CN), 21.1 (2C, CH2eCeCF3), 24.2 (2C, CH3), 32.0
(2C, CH2 cyclohexyl), 39.1 (2C, CH2eCN cyclohexyl), 64.3
(2C, CHeN cyclohexyl), 122.0 (2C, CO), 126.0 (q, 2C). 19F
NMR (182 MHz, CDCl3): d ꢀ78.74 (q, J¼10.35, 6F),
ꢀ79.22 (q, J¼10.35, 6F).
˚
let apparatus charged with 5 A molecular sieves (10.0 g).
Compound 2j was obtained as a pale yellow oil (2.24 g,
1
74%). H NMR (200 MHz, CDCl3): d 1.83 (m, 6H, 3CH2 of
piperidine), 2.80 (m, 2H, CH2 of piperidine), 3.02 (s, 2H,
CH2), 3.40 (m, 1H, CH of piperidine), 3.51 (s, 2H, CH2ePh),
7.33 (m, 10H, arom.), 10.36 (s, 1H, OH). 19F NMR (188 MHz,
CDCl3): d ꢀ78.24 (s, 6F). 13C NMR (75 MHz, CDCl3):
d 32.96 (s, C, CH2ePh), 51.49 (s, C, CH2), 30.14, 33.19,
52.55, 58.09, 63.54 (s, 5C of piperidine), 125.97, 127.11,
127.42, 128.63, 129.51, 129.56, 129.71, 130.08, 136.69,
138.80 (14C of Ph groups), 169.14 (s, C, C]N). Resonances
for CF3 groups were not observed due to a too short relaxation
period or a non-adapted pulse angle. Anal. Calcd for
C24H27F6N2O: C, 60.88; H, 5.75. Found: C, 70.10; H, 5.42.
4.2.17. 1,1,1-Trifluoro-4-[(2-{[4,4,4-trifluoro-3-hydroxy-1-
methyl-3-(trifluoromethyl)butylidene]amino}propyl)imino]-
2-(trifluoromethyl)pentan-2-ol (3d)
This compound was prepared by following the same proce-
dure as that described above for 2d, starting from 1a (1.77 g,
7.9 mmol), 1,3-propanediamine (335 mL, 4.0 mmol), and
montmorillonite (0.50 g), reacting in chloroform (5 mL) for
3 days at 70 ꢁC. Compound 3d was obtained as a colorless
oil that crystallizes (1.00 g, 52%). Mp¼30 ꢁC. 1H NMR
4.2.14. 1,1,1-Trifluoro-4-[(2-{[4,4,4-trifluoro-3-hydroxy-1-
methyl-3-(trifluoromethyl)butylidene]amino}ethyl)imino]-
2-(trifluoromethyl)pentan-2-ol (3a)
This compound was prepared by following the same proce-
dure as that described above for 2d, starting from 1a (2.75 g,
12.3 mmol) and 1,2-ethylenediamine (0.36 g, 6.1 mmol), in
the presence of montmorillonite (0.80 g), reacting for 72 h in
chloroform (10 mL). Compound 3a was obtained as an orange
solid (3.88 g, 69%) by recrystallization of the crude product
3
(200 MHz, CDCl3): d 2.01 (s, 6H, CH3), 2.01 (qt, JHH¼6.6,
2H, CH2eCH2eCH2), 2.73 (s, 4H, CH2eC]N), 3.42 (t, 3JHH
¼
6.6, 4H, CH2eN), 10.0 (br s, 2H, OH). 13C NMR (75 MHz,
CDCl3): d 20.1 (s, 2C, CH3), 30.2 (s, 1C, CH2eCH2eCH2),
33.0 (s, 2C, CH2eC]N), 47.4 (s, 2C, CH2eN), 76.6 (hept,
1
1
from methanol. H NMR (500 MHz, CDCl3): d 2.04 (s, 6H,
2JCF¼29.3, C(CF3)2), 123.2 (q, JCF¼288.7, 4C, CF3), 170.8
Me), 2.73 (s, 4H, CH2), 3.66 (s, 4H, CH2N), 9.88 (s, 2H, OH).
13C NMR (75 MHz, CDCl3): d 20.63 (CH2), 33.41 (Me), 50.42
(CH2eN), 121.1 (CeOH), 125.5 (CeF), 171.42 (C]N). 19F
(s, 2C, C]N). 19F NMR (188 MHz, CDCl3): d ꢀ78.9 (s,
12F). HRMS (70 eV, EI): m/z calcd for C15H18N2O2F12
ꢂ
[Mþ ]: 486.11767; found: 486.1202 (5 ppm).