P. Roszkowski et al. / Tetrahedron: Asymmetry 23 (2012) 1106–1110
1109
1
3
43.5, 148.2. HRMS: m/z calcd for C17
71.1518; found: 371.1526.
Monocrystals of 3a suitable for crystallographic measurements
H
24
N
4
O
2
NaS [M+Na]+:
at room temperature for 15 h. The ethanolic solution was filtered
and the solvent evaporated in vacuo. After the addition of diethyl
ether to the residual oil, a solid was formed. The filtration of crys-
tals gave 1.06 g (95%) of compound 4b as a colourless solid;
were obtained from hexane solution by slow evaporation. The
absolute structure of the crystal was studied, and hence the abso-
lute configuration of the compound was determined based on the
value of the Flack parameter.16 Since its value for the structure
shown in Fig. 1 was approximately 0, the molecular structure has
the depicted configuration. The data were deposited with Cam-
bridge Crystallographic Data Centre under the number CCDC
2
3
½
a
ꢂ
¼ ꢀ10:4 (c 1.0, CHCl
3
), mp = 113–114 °C. The enantiomeric
purity was determined by HPLC [Chiracel OD-H, hexane/i-PrOH
(90:10), 1 mL/min]; the (1R,2R,4R)-isomer eluted at 15.5 min. 1
NMR (CDCl , 500 MHz): d 0.69 (d, 3H, J = 6.5 Hz), 0.73 (d, 3H,
D
H
3
J = 7.0 Hz), 0.83–0.91 (m, 1H), 0.93 (s, 3H), 1.00–1.06 (m, 1H),
1.18–1.41 (m, 4H), 1.50–1.53 (m, 1H), 1.68 (dt, 1H, J = 13.5,
3.0 Hz), 2.42 (s, 3H), 2.80 (dd, 1H, J = 12.0, 4.0 Hz), 4.74 (bs, 1H),
8
58075.
1
3
7
3
.31 (d, 2H, J = 8.0 Hz), 7.81 (d, 2H, J = 8.0 Hz); C NMR (CDCl ,
4
4
.1.3. (1R,2R,5R)-N-(2-Azido-5-isopropenyl-2-methyl-cyclohexyl)-
-methyl-benzenesulfonamide 3b
Isomer 3b was obtained in the same reaction as isomer 3a. This
125 MHz): d 19.5, 19.7, 19.9, 21.5, 25.9, 32.1, 33.3, 40.7, 43.6,
51.9, 63.2, 127.1, 129.7, 137.7, 143.4. HRMS: m/z calcd for
+
C
17
29
H N
2
O
2
S [M+H] : 325.1950; found: 325.1953.
compound was isolated by column chromatography on silica gel
using a more polar mobile phase based on hexane/ethyl acetate
4
.1.6. General procedure for the synthesis of catalysts 5–7
A mixture of [RuCl (C )] (6 mg, 12 mol) or [RuCl (p-cym-
ene)]2 (7.3 mg, 12 mol, ligands 4a or 4b (9.7 mg, 30 mol) and
Et N (24 mol) in 1 mL of CH CN was stirred at room tempera-
(
8–10% of ethyl acetate). The separation gave 2.11 g (12%) of com-
2
6
H
6
2
l
2
23
pound 3a as colourless crystals; ½
a
ꢂ
¼ ꢀ54:0 (c 1.0, CHCl
3
),
D
l
l
mp = 126–127 °C. The enantiomeric purity was determined by
HPLC [Chiracel OD-H, hexane/i-PrOH (90:10), 1 mL/min]; the
3
l
3
ture for 30 min. After this time, the resulting pale brown solu-
tion of catalyst was used immediately for the reduction of the
ketones.
(
1R,2R,4R)-isomer eluted at 11.5 min. 1H NMR (CDCl
3
, 500 MHz):
d 1.21 (s, 3H), 1.24–1.30 (m, 2H), 1.51–1.57 (m, 1H), 1.63 (s, 3H),
1
.65–1.70 (m, 1H), 1.81 (dt, 1H, J = 13.0, 3.0 Hz), 1.89–1.91 (m,
2
H), 2.42 (s, 3H), 3.19 (m, 1H), 4.63 (s, 1H), 4.69 (t, 1H,
4
.1.7. General procedure for ketones reduction using catalysts
5–7
To a ketone (2.4 mmol) placed in a vial 1 mL of CH
of the preformed ruthenium catalyst (24 mol) and formic acid/tri-
J = 1.5 Hz), 4.86 (d, 1H, J = 8.0 Hz), 7.31 (d, 2H, J = 8.0 Hz), 7.81 (d,
1
3
2
2
1
H, J = 8.0 Hz); C NMR (CDCl
3
, 125 MHz): d 16.6, 21.1, 21.8,
3
CN solution
7.3, 35.6, 36.9, 43.8, 59.6, 63.2, 109.8, 127.4, 129.8, 137.8, 143.7,
47.7. HRMS: m/z calcd for C17H N O NaS [M+Na] : 371.1518;
24 4 2
+
l
ethylamine azeotropic mixture (1 mL) were added. The mixture
was then stirred at room temperature and the progress of the reac-
tion was monitored by TLC until the specified conversion was
found: 371.1530.
Monocrystals of 3b suitable for crystallographic measurements
were obtained from diethyl ether/hexane solution by slow evapo-
ration. The absolute structure of the crystal was studied, and hence
achieved. After evaporation of the solvents, 4 mL of CH
.5 mL of 10% aqueous HCl solution were added to the residue.
The layers were separated and the water layer was extracted twice
with 2 mL of CH Cl . The combined organic layers were dried over
Na SO and the solvent was evaporated in vacuo. The residual oil
was purified by column chromatography on silica gel using
chloroform (dried over CaCl ) as eluent to afford the appropriate
alcohol. The enantiomeric excess was determined by GC analysis
using Supelco cyclodextrin b-DEX 120 capillary column
m film thickness). The results of
2 2
Cl and
1
the absolute configuration of the compound was determined based
on the value of the Flack parameter.16 Since its value for the struc-
2
2
ture shown in Figure 2 was approximately 0, the molecular struc-
ture has the depicted configuration. The data were deposited with
Cambridge Crystallographic Data Centre under the number CCDC
2
4
2
8
58076.
a
4
4
.1.4. (1S,2S,4R)-N-(2-Amino-4-isopropyl-1-methyl-cyclohexyl)-
-methyl-benzenesulfonamide 4a
(
20 m ꢄ 0.25 mm ID and 0.25
l
the reduction are summarized in Table 1.
To a stirred solution of azide 3a (2.0 g, 5.74 mmol) in anhydrous
ethanol (100 mL) was added palladium on carbon-10% (400 mg)
and the resulting suspension was shaken in an atmosphere of
hydrogen at room temperature for 15 h. The ethanolic solution
was filtered and the solvent evaporated in vacuo. After the addition
of diethyl ether to the residual oil, a solid was formed. The filtration
of crystals gave 1.77 g (95%) of compound 4a as a colourless solid;
Acknowledgments
We acknowledge the financial support from the Polish Ministry
of Science and Higher Education in the form of Grant No. N204
2
117939. We cordially thank Dr. Dariusz Błachut (Internal Security
23
Agency) for the determination of ee values by GC.
½
a
ꢂ
¼ þ18:6 (c 1.0, CHCl
3
); mp = 112–113 °C. The enantiomeric
D
purity was determined by HPLC [Chiracel OD-H, hexane/i-PrOH
1
(
90:10), 1 mL/min]; the (1S,2S,4R)-isomer eluted at 16.7 min.
NMR (CDCl , 500 MHz): d 0.80 (d, 3H J = 6.5 Hz), 0.82 (d, 3H,
J = 7.0 Hz), 1.06–1.11 (m, 2H), 1.13 (s, 3H), 1.23–1.27 (m, 1H),
.34–1.46 (m, 3H), 1.61–1.68 (m, 2H), 2.42 (s, 3H), 2.98 (dd, 1H,
J = 6.0, 3.5 Hz), 5.03 (bs, 1H), 7.29 (d, 2H, J = 8.0 Hz), 7.78 (d, 2H,
H
References
3
1.
(a) Pawson, B. A.; Cheung, H-C.; Gurbaxani, S.; Saucy, G. J. Am. Chem. Soc. 1970,
2, 336–343; (b) Van Tamelen, E. E.; Anderson, R. J. J. Am. Chem. Soc. 1972, 94,
225–8228; (c) Mori, K.; Kato, M. Tetrahedron 1986, 42, 5895–5900; (d)
9
8
1
Marron, B. E.; Nicolaou, K. C. Synthesis 1989, 7, 537–540; (e) Tius, M. A.; Kerr, M.
A. Synth. Commun. 1988, 18, 1905–1911; (f) Baudouy, R.; Prince, P. Tetrahedron
1
3
J = 8.5 Hz); C NMR (CDCl
3
, 125 MHz): d 20.2, 20.3, 21.5, 24.1,
1989, 45, 2067–2074; (g) Paquette, L. A.; Kang, H-J J. Am. Chem. Soc. 1991, 113,
2
5.4, 32.1, 36.3, 42.3, 53.1, 57.5, 60.1, 126.9, 129.5, 140.8, 142.8.
2610–2621.
+
HRMS: m/z calcd for C17
H
29
N
2
O
2
S [M+H] : 325.1950; found:
2. (a) Goralski, C. T.; Chrisman, W.; Hasha, D. L.; Nicholson, L. W.; Rudolf, P. R.;
Zakett, D.; Singaram Tetrahedron: Asymmetry 1997, 8, 3863–3871; (b) Steiner,
D.; Sethofer, S. G.; Goralski, C. T.; Singaram, B. Tetrahedron: Asymmetry 2002, 13,
3
25.1962.
1
477–1483; (c) Masui, M.; Shioiri, T. Tetrahedron 1995, 51, 8363–8370; (d)
4
4
.1.5. (1R,2R,5R)-N-(2-Amino-5-isopropyl-2-methyl-cyclohexyl)-
-methyl-benzenesulfonamide 4b
To a stirred solution of azide 3a (1.2 g, 3.44 mmol) in anhydrous
Kauffman, G. S.; Harris, G. D.; Dorow, L. R.; Stone, B. R. P.; Parsons, R. L., Jr.; Pesti,
J. A.; Magnus, N. A.; Fortunak, J. M.; Confalone, P. N.; Nugent, W. A. Org. Lett.
2000, 2, 3119–3121; (e) Bennani, Y. L.; Hanessian, S. Chem. Rev. 1997, 97, 3161–
3195; (f) Larionov, S. V.; Tkachev, A. V.; Myachina, L. I.; Savel’eva, Z. A.;
ethanol (60 mL) was added palladium on carbon-10% (240 mg) and
the resulting suspension was shaken in an atmosphere of hydrogen
Glinskaya, L. A.; Klevtsova, R. F.; Agafontsev, A. M.; Bizyaev, S. N. Russ. J. Coord.
Chem. 2009, 35, 286–295.