_
´
/ Tetrahedron: Asymmetry 19 (2008) 2252–2257
E. Wojaczynska, J. Skarzewski
2256
1135, 1284, 1453, 1491, 2860, 2930, 3024, 3060 cmꢁ1. HRMS (ESI):
493.2712 ([M+H]+); for (C30H41N2S2)+ M = 493.27112.
4.7.2.2. (1S,3R,4R)-2-[(S)-1-Phenylethyl]-3-(2-dithiolate)-2-aza-
bicyclo[2.2.1]heptane 12b.
Yield 32%, ½a 2D0
¼ þ3:4 (c 0.74,
ꢀ
CH2Cl2), 1H NMR (CDCl3, 300 MHz): d 1.09–1.13 (m, 1H), 1.18–
1.35 (m, 4H), 1.50–1.55 (m, 2H), 1.75–1.85 (m, 1H), 2.20–2.26
(m, 2H), 2.36–2.38 (m, 1H), 2.82–2.90 (m, 2H), 2.95–3.02 (m,
2H), 3.37–3.38 (d, 1H, J = 3.32 Hz), 3.42 (q, 1H, J = 6.56 Hz), 3.58
(br s, 1H), 7.17–7.32 (m, 5 H, ArH) ppm. 13C NMR (CDCl3): d 21.7,
21.9, 29.3, 35.7, 37.2, 38.5, 56.3, 58.1, 60.4, 72.1, 126.9, 127.3,
127.5, 145.3 ppm. IR (film) 701, 768, 1106, 1163, 1304, 1453,
1492, 1674, 1720, 2869, 2922, 2971, 3026, 3061 cmꢁ1. HRMS
(ESI): 306.1309 ([M+H]+); for (C17H24NS2)+ M = 306.13501.
4.7. Oxidation of alcohol 4b and further modifications
Oxidation of 4b under Swern conditions led to (1S,3R,4R)-2-[(S)-
1-phenylethyl]-2-azabicyclo[2.2.1]heptane-3-carbaldehyde 8b as
described in the literature.7b,10a
4.7.1. Preparation of Schiff base
Aldehyde 8b (0.10 g, 0.43 mmol) and (S)-1-phenylethylamine
(0.054 mL, 0.43 mmol) were dissolved in 5 mL of ethanol, and the
mixture was left over MgSO4 for 24 h. The solvent was evaporated
and the residue was chromatographed on neutral alumina column
(hexane–ethyl acetate (5:1 v/v). Compound 10b was obtained in a
similar manner using (R)-1-phenylethylamine instead of its
enantiomer.
4.8. Catalytic reactions
The Pd-catalyzed allylic substitution reaction of dimethyl mal-
onate with rac-1,3-diphenyl-2-propenyl acetate was performed
using 3 mol % of N,O-bis(trimethylsilyl)acetamide-potassium ace-
tate as a base, 2.5 mol % of [Pd(g
3-C3H5)Cl]2, and 10 mol % of the
4.7.1.1. (1S,3R,4R)-2-[(S)-1-Phenylethyl]-3-[(S)-1-phenylethylim-
chiral ligand tested in acetonitrile solution. The stereochemical
effect of the catalytic reaction was determined by 1H NMR mea-
surement using Eu(hfc)3 as a chiral shift reagent. The assignment
of absolute configuration was based on the specific rotation
according to the literature data.14
ine]methyl-2-azabicyclo[2.2.1]heptane
9b.
Yield
56%,
½
a 2D0
ꢀ
¼ ꢁ2:5 (c 1.58, CH2Cl2), 1H NMR (CDCl3, 300 MHz):
d
1.20–1.41 (m, 8H), 1.48 (d, 1H, J = 6.55 Hz), 1.54–1.59 (m, 2H),
1.71–1.75 (m, 1H), 1.91–1.96 (m, 1H), 2.24–2.27 (m, 1H), 2.62 (d,
1H, J = 5.38 Hz), 3.46 (q, 1H, J = 6.48 Hz), 3.65 (br s, 1H), 3.80 (q,
1H, J = 6.68 Hz), 6.81–7.40 (m, 10H, ArH) ppm. 13C NMR (CDCl3):
d 21.5, 21.8, 22.7, 28.2, 35.0, 43.1, 57.7, 59.9, 67.4, 70.5, 125.4,
125.7, 126.1, 126.8, 127.0, 127.0, 143.2, 144.1, 166.8 ppm. IR
(film) 699, 759, 1370, 1451, 1662, 1687, 2869, 2966, 3027,
Acknowledgment
We are grateful to the Ministry of Science and Higher Education
for financial support (Grant PBZ-KBN-126/T09/2004).
3062 cmꢁ1
.
HRMS (ESI): 333.2293 ([M+H]+); for (C23H29N2)+
M = 333.2306.
References
4.7.1.2. (1S,3R,4R)-2-[(S)-1-Phenylethyl]-3-[(R)-1-phenylethyli-
1. (a) New Frontiers in Asymmetric Catalysis; Mikami, K., Lautens, M., Eds.; Wiley-
Interscience: Hoboken, 2007; (b) Catalytic Asymmetric Synthesis; Ojima, I., Ed.;
Wiley-VCH: New York, 2000; (c) Comprehensive Asymmetric Catalysis; Jacobsen,
E. N., Pfalz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999, Vols. 1–3.
2. Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691–1693.
3. (a) Bailey, P. D.; Wilson, R. D.; Brown, G. R. Tetrahedron Lett. 1989, 30, 6781–
6784; (b) Nakano, H.; Kumagai, N.; Kabuto, C.; Matsuzaki, H.; Hongo, H.
Tetrahedron: Asymmetry 1995, 6, 1233–1236; (c) Brandt, P.; Andersson, P. G.
Synlett 2000, 1092–1106.
4. (a) Alonso, D. A.; Bertilsson, S. K.; Johnsson, S. Y.; Nordin, S. J. M.; Södergren, M.
J.; Andersson, P. G. J. Org. Chem. 1999, 64, 2276–2280; (b) Alonso, D. A.; Nordin,
S. J. M.; Andersson, P. G. Org. Lett. 1999, 1, 1595–1597; (c) Hedberg, C.; Pinho,
P.; Roth, P.; Andersson, P. G. J. Org. Chem. 2000, 65, 2810–2812; (d) Modin, S. A.;
Andersson, P. G. J. Org. Chem. 2000, 65, 6736–6738; (e) Nordin, S. J. M.; Roth, P.;
Tarnai, T.; Alonso, D. A.; Brandt, P.; Andersson, P. G. Chem. Eur. J. 2001, 7, 1431–
1436; (f) Bertilsson, S. K.; Ekegren, J. K.; Modin, S. A.; Andersson, P. G.
Tetrahedron 2001, 57, 6399–6406; (g) Ekegren, J. K.; Modin, S. A.; Alonso, D. A.;
Andersson, P. G. Tetrahedron: Asymmetry 2002, 13, 447–449; (h) Ekegren, J. K.;
Roth, P.; Källström, K.; Tarnai, T.; Andersson, P. G. Org. Biomol. Chem. 2003, 1,
358–366; (i) Trifonova, A.; Andersson, P. G. Tetrahedron: Asymmetry 2004, 15,
445–452.
5. (a) Alonso, D. A.; Guijarro, D.; Pinho, P.; Temme, O.; Andersson, P. G. J. Org.
Chem. 1998, 63, 2749–2751; (b) Alonso, D. A.; Nordin, S. J. M.; Roth, P.; Tarnai,
T.; Andersson, P. G.; Thommen, M.; Pittelkow, U. J. Org. Chem. 2000, 65, 3116–
3122; (c) Brandt, P.; Roth, P.; Andersson, P. G. J. Org. Chem. 2004, 69, 4885–
4890; (d) Trifonova, A.; Diesen, J. S.; Chapman, C. J.; Andersson, P. G. Org. Lett.
2004, 6, 3825–3827; (e) Trifonova, A.; Källström, K.; Andersson, P. G.
Tetrahedron 2004, 60, 3393–3403; (f) Trifonova, A.; Diesen, J. S.; Andersson, P.
G. Chem. Eur. J. 2006, 12, 2318–2328.
mine]methyl-2-azabicyclo[2.2.1]heptane 10b.
Yield 39%,
½
a 2D0
ꢀ
¼ þ52:9 (c 0.44, CH2Cl2), 1H NMR (CDCl3, 300 MHz): d 1.16–
1.36 (m, 9H), 1.51–1.54 (m, 2H), 1.63–1.66 (m, 1H), 1.92–1.97
(m, 1H), 2.14–2.18 (m, 1H), 2.63 (d, 1H, J = 5.64 Hz), 3.49 (q, 1H,
J = 6.50 Hz), 3.64 (br s, 1H), 3.74 (q, 1H, J = 6.62 Hz), 7.02–7.30
(m, 10H, ArH) ppm. 13C NMR (CDCl3): d 21.5, 21.8, 22.9, 28.4,
35.1, 43.3, 57.6, 59.9, 67.5, 70.7, 125.3, 125.5, 126.1, 127.2, 127.3,
127.6, 144.2, 144.6, 167.2 ppm. IR (film) 701, 763, 1383, 1451,
1661, 1687, 2869, 2968, 3029, 3061 cmꢁ1. HRMS (ESI): 333.2286
([M+H]+); for (C23H29N2)+ M = 333.2306.
4.7.2. Preparation of dithioacetals
To a stirred solution of aldehyde 8b (80 mg, 0.35 mmol) and
ethanedithiol or 1,3-propanedithiol (0.035 mL, 0.35 mmol) in
5 mL of chloroform 0.1 mL of BF3ꢂEt2O was added by syringe. A
solution was kept over anhydrous sodium sulfate for 24 h. After fil-
tration, the reaction mixture was subsequently washed with water,
aqueous NaOH (5%), water and saturated aqueous NaCl and dried
with Na2SO4. After removal of solvent, the residue was chromato-
graphed on silica column. Elution with chloroform yielded dithio-
acetal 11b or 12b.
6. Pinho, P.; Guijarro, D.; Andersson, P. G. Tetrahedron 1998, 54, 7897–
7906.
7. (a) Guijarro, D.; Pinho, P.; Andersson, P. G. J. Org. Chem. 1998, 63, 2530–2535;
(b) Brandt, P.; Hedberg, C.; Lawonn, K.; Pinho, P.; Andersson, P. G. Chem. Eur. J.
1999, 5, 1692–1699; (c) Pinho, P.; Andersson, P. G. Tetrahedron 2001, 57, 1615–
1618.
8. Södergren, M. J.; Andersson, P. G. Tetrahedron Lett. 1996, 37, 7577–7580.
9. Bertilsson, S. K.; Andersson, P. G. J. Organomet. Chem. 2000, 603, 13–17.
10. (a) Södergren, M. J.; Andersson, P. G. J. Am. Chem. Soc. 1998, 120, 10760–10761;
(b) Södergren, M. J.; Bertilsson, S. K.; Andersson, P. G. J. Am. Chem. Soc. 2000,
122, 6610–6618; (c) Magnus, A.; Bertilsson, S. K.; Andersson, P. G. Chem. Soc.
Rev. 2002, 31, 223–229; (d) Bertilsson, S. K.; Södergren, M. J.; Andersson, P. G. J.
Org. Chem. 2002, 67, 1567–1573; (e) Gayet, A.; Bertilsson, S. K.; Andersson, P. G.
Org. Lett. 2002, 4, 3777–3779; (f) Bertilsson, S. K.; Andersson, P. G. Tetrahedron
2002, 58, 4665–4668; (g) Gayet, A.; Andersson, P. G. Tetrahedron Lett. 2005, 46,
4805–4807.
4.7.2.1. (1S,3R,4R)-2-[(S)-1-Phenylethyl]-3-(2-dithiane)-2-aza-
bicyclo[2.2.1]heptane 11b.
Yield 81%, ½a 2D0
¼ þ18:4 (c 0.68,
ꢀ
CH2Cl2), 1H NMR (CDCl3, 300 MHz):
d 1.05–1.07 (m, 1H),
1.15–1.28 (m, 5H), 1.48–1.53 (m, 2H), 1.75–1.81 (m, 2H), 1.88–
1.91 (m, 1H), 2.07–2.14 (m, 3H), 2.29–2.30 (m, 1H), 2.40–2.47
(m, 2H), 2.56–2.60 (m, 1H), 3.39 (q, 1H, J = 6.54 Hz), 3.59 (br
s, 1H), 7.17–7.21 (m, 3H, ArH), 7.33–7.36 (m, 2H, ArH) ppm.
13C NMR (CDCl3): d 21.9, 22.6, 26.8, 30.4, 31.5, 31.8, 36.5, 39.9,
54.7, 58.2, 61.4, 72.9, 127.2, 128.0, 128.4, 146.4 ppm. IR
(film) 700, 769, 1163, 1299, 1452, 2826, 2870, 2895, 2969,
3025 cmꢁ1. HRMS (ESI): 320.1553 ([M+H]+); for (C18H26NS2)+
M = 320.15067.