A. Lattanzi, S. Piccirillo, A. Scettri
FULL PAPER
Kuhn, C. Palazzi, W. Adam, B. P. Rao, C. R. Saha-Möller, Tet-
rahedron: Asymmetry 2001, 12, 2441.
H), 2.96–2.89 (m, 1 H). HPLC: tr(R) = 24.2 min, tr(S) = 19.6 min
(Chiralcel OD; flow rate 0.5 mL/min; hexane/iPrOH, 7:3).
[2] a) R. A. Johnson, K. B. Sharpless, Catalytic Asymmetric Syn-
thesis (Ed.: I. Ojima), Wiley-VCH, New York, 2000, pp. 231;
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W. Adam, P. L. Alsters, R. Neumann, C. R. Saha-Möller, D.
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2004, 15, 1779.
trans-(S,S)-2-(4Ј-Methoxyphenyl)-1,3-dithiane 1-Oxide (8i): 1H
NMR (400 MHz, ppm): δ = 7.35–7.32 (m, 2 H), 6.92–6.90 (m, 2
H), 4.51 (s, 1 H), 3.80 (s, 3 H), 3.59–3.51 (m, 1 H), 2.93–2.62 (m,
3 H), 2.56–2.26 (m, 2 H). HPLC: tr(R) = 44.6 min, tr(S) = 24.3 min
(Chiralcel OD; flow rate 0.5 mL/min; hexane/iPrOH, 7:3).
trans-(S,S)-2-(4Ј-Methylphenyl)-1,3-dithiane 1-Oxide (8j): 1H NMR
(400 MHz, ppm): δ = 7.34–7.13 (m, 4 H), 4.52 (s, 1 H), 3.59–3.50
(m, 1 H), 2.92–2.22 (m, 5 H), 2.34 (s, 3 H). HPLC: tr(R) = 21.9 min,
tr(S) = 10.5 min (Chiralcel OD; flow rate 0.8 mL/min; hexane/iP-
rOH, 7:3).
trans-(S,S)-2-(4Ј-Chlorophenyl)-1,3-dithiane 1-Oxide (8k): 1H NMR
(400 MHz, ppm): δ = 7.38–7.35 (m, 4 H), 4.54 (s, 1 H), 3.61–3.51
(m, 1 H), 2.83–2.63 (m, 3 H), 2.56–2.26 (m, 2 H). HPLC: tr(R) =
36.0 min, tr(S) = 11.4 min (Chiralcel OD; flow rate 0.8 mL/min;
hexane/iPrOH, 7:3).
trans-(R,R)-2-Methyl-2-phenyl-1,3-dithiane 1-Oxide (trans-8l): 1H
NMR (400 MHz, ppm): δ = 7.66 (m, 2 H), 7.41 (m, 2 H), 7.33 (m,
2 H), 2.88–2.60 (m, 4 H), 2.53–2.43 (m, 1 H), 2.09–1.96 (m, 1 H),
1.92 (s, 3 H). HPLC: tr(R,R) = 16.9 min, tr(S,S) = 22.5 min (Chi-
ralcel OD; flow rate 0.5 mL/min; hexane/iPrOH, 7:3).
[6] A. Lattanzi, M. Cocilova, P. Iannece, A. Scettri, Tetrahedron:
Asymmetry 2004, 15, 3751.
[7] A. Lattanzi, S. Piccirillo, A. Scettri, Eur. J. Org. Chem. 2005,
8, 1669.
[8] A. Lattanzi, P. Iannece, A. Scettri, Tetrahedron: Asymmetry
2004, 15, 413.
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J. Vaysse, T. A. Brauchek, C. Gluchowski, J. Med. Chem. 2000,
43, 1699.
cis-2-Methyl-2-phenyl-1,3-dithiane 1-Oxide (cis-8l): 1H NMR
(400 MHz, ppm): δ = 8.00 (m, 2 H), 7.43 (m, 2 H), 7.36 (m, 1 H),
2.91 (m, 1 H), 2.79–2.65 (m, 2 H), 2.47–2.28 (m, 3 H), 1.93 (s, 3
H).
[10]
a) S. Ikegami, D. L. Vander Jagt, H. C. Brown, J. Am. Chem.
Soc. 1968, 90, 7124; b) H. L. Goering, H. C. Brown, C. B.
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General Procedure for Kinetic Resolution: To a stirred solution
Ti(OiPr)4 (60.4 µL, 0.205 mmol) in anhydrous toluene (0.7 mL) a
solution of the racemic sulfoxide ( )-8a (109 mg, 0.709 mmol) in
anhydrous toluene (1 mL) was added under argon atmosphere at
–20 °C. The mixture was stirred for 10 min at –20 °C and then was
added a solution of 3 (68 mg, 0.327 mmol) in anhydrous toluene
(1.5 mL). The reaction progress was monitored by TLC analysis.
At the end of the reaction, water (240 µL) was added and the mix-
ture was stirred for 1 h at room temperature. After filtration of the
mixture over a celite bed with ethyl acetate (70 mL), the solvent
was evaporated under vacuum and the crude reaction mixture was
purified by flash chromatography (from petroleum ether/diethyl
ether mixtures 90:10 to pure ethyl acetate) to give (+)-exo-5 (65–75
mol-% recovery with respect to 3) and (R)-8a as white solid; yield
59 mg (54%).
[11] M. Kawamura, K. Ogasawara, Tetrahedron Lett. 1995, 36,
3369.
[12] D. A. Lightner, T. D. Bouman, B. V. Crist, S. L. Rodgers, M. A.
Knobeloch, A. M. Jones, J. Am. Chem. Soc. 1987, 109, 6248.
[13] NOESY experiment on the diastereoisomeric mixture of the
alcohols 5 showed correlation peaks between the methyl group
at position 3 and the hydrogens on the furyl ring for the most
abundant diastereoisomer, thus confirming that these two
groups are in a cis relationship. The absence of any peak of
correlation for the methyl group with hydrogens on the furyl
ring was observed in the case of the minor diastereoisomer,
which confirmed that the two groups are in a trans relationship.
[14] The tertiary 2Ј-furyl-2-norbornyl cation was found to be stabi-
lized by the charge-delocalizing ability of the furyl system. It
has been reported that there is substantial π-bond character
between C-2 of the furyl moiety and the cationic carbon, see:
G. A. Olah, A. L. Berrier, G. K. S. Prakash, J. Org. Chem.
1982, 47, 3903.
Acknowledgments
[15] a) I. Fernández, N. Khiar, Chem. Rev. 2003, 103, 3651; b)
A. M. Rouhi, Chem. Eng. News 2003, 81, 56; c) J. Legros, J. R.
Dehli, C. Bolm, Adv. Synth. Catal. 2005, 347, 19.
Ministero dell’Università
e Ricerca Scientifica e Tecnologica
(MIUR) is gratefully acknowledged for financial support. We
thank Prof. C. Bolm for the HPLC conditions of dithiane and di-
thiolane mono-sulfoxides.
[16] For recent reviews on asymmetric metal-catalyzed sulfoxid-
ation, see: a) H. B. Kagan, T. O. Luukas, in: Transition Metals
for Organic Synthesis, vol. 2, 2nd edition (Eds.: M. Beller, C.
Bolm), Wiley-VCH, Weinheim, 2004, pp. 479; b) C. Bolm, Co-
ord. Chem. Rev. 2003, 237, 245; c) K. P. Volcho, N. F. Salakhut-
dinov, A. G. Tolstikov, Russ. J. Org. Chem. 2003, 39, 1537.
[17] H. B. Kagan, J. C. Fiaud, Top. Stereochem. 1988, 18, 249.
[18] Alcohol exo-5 was recovered during the purification procedure
(flash chromatography) in 65–75% yield and recycled for the
synthesis of 3, thus making the entire process more convenient.
Received: September 6, 2005
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Published Online: November 30, 2005
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Eur. J. Org. Chem. 2006, 713–718