LETTER
Synthesis of Isocyclocapitelline Derivatives from (3R)-Linalool
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Hz, 1 H), 4.98 (dd, J = 11, 2 Hz, 1 H), 5.18 (dd, J = 17, 2 Hz,
1 H), 5.85 (dd, J = 17, 11 Hz, 1 H).
(17) (a) Castrette, M.; Axiotis, G. P. J. Organometal. Chem.
1981, 206, 139. (b) David, L.; Veschambre, H. Tetrahedron
Lett. 1984, 25, 543.
References
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Merzweiler, K.; Adam, G. Phytochemistry 1999, 52, 1725.
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Phytochemistry 1997, 46, 1119.
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209, 3. (b) Winterhalter, P.; Katzenberger, D.; Schreier, P.
Phytochemistry 1986, 25, 1347.
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X. T. Tetrahedron Lett. 2000, 41, 2211. (b) Wang, G. X.;
Zhang, J. X.; Chen, S. F.; Liang, X. T. Chin. Chem. Lett.
2001, 12, 199. (c) Mahboobi, S.; Koller, M.; Schollmeyer,
D. Monatsh. Chem. 2000, 131, 383.
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1964, 675, 73. (b) Prileschajew, N. Ber. Dtsch.Chem. Ges.
1909, 42, 4811.
(18) Control experiments14 indicated that vanadium(V) complex
4b catalyzes oxidation of racemic mixtures of chiral
bishomoallylic alcohols without kinetic resolution.
(19) Tungsten-catalyzed oxidations: (a) Sakaguchi, S.;
Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1996, 61, 5307.
(b) Villa de, O. A. L.; Sels, B. F.; De Vos, D. E.; Jacobs, P.
A. J. Org. Chem. 1999, 64, 7267.
(20) Lempers, H. E. B.; Ripollès i Garcia, A.; Sheldon, R. A. J.
Org. Chem. 1998, 63, 1408.
(21) Titanium and titanium silicate-catalyzed oxidations:
(a) Schofield, L. J.; Kerton, W. J.; McMorn, P.; Bethell, D.;
Ellwood, S.; Hutchings, G. J. J. Chem. Soc., Perkin Trans. 2
2002, 1475. (b) Lattanzi, A.; Della Sala, G.; Russo, M.;
Scettri, A. Synlett 2001, 1479. (c) Corma, A.; Iglesias, M.;
Sánchez, F. J. Chem. Soc., Chemm. Commun. 1995, 1635.
(22) Felix, D.; Malera, A.; Seibl, J.; Kováts, E. Helv. Chim. Acta
1963, 46, 1513.
(6) Villa de, ; De Vos, D. E.; Montes de, C. C.; Jacobs, A.
Tetrahedron Lett. 1998, 39, 8521.
(7) (a) Sams, C. K.; Jørgensen, K. A. Acta Chim. Scand. 1995,
49, 839. (b) Sheldon, R. A. In The Chemistry of Functional
Groups, Peroxides; Patai, S., Ed.; Wiley: Chichester, 1983,
161–199. (c) Sharpless, K. B.; Verhoeven, T. R.
(23) Yang, D.; Zhang, C. J. Org. Chem. 2001, 66, 4814.
(24) cis-1-[5-(1-Hydroxy-1-methylethyl)-2-methyltetrahydro-
furan-2-yl]-1,2,3,4-tetrahydro-9H-β-carboline: colorless
crystals, mp 119 °C; [α]D25 –22.9 (c 0.82, CHCl3). 1H NMR
(250 MHz, CDCl3): δ = 1.08 (s, 3 H), 1.24 (s, 3 H), 1.38 (s,
3 H), 1.80–2.16 (m, 4 H), 2.78 (ddd, J = 12.1, 7.9, 5.5 Hz, 2
H), 3.21 (ddd, J = 12.5, 9.8, 5.5 Hz, 2 H), 4.02 (t, J = 7.0 Hz,
1 H), 4.06 (s, 1 H), 7.00–7.19 (m, 2 H), 7.24–7.36 (m, 1 H),
Aldrichimica Acta 1979, 12, 63.
(8) (a) Ohloff, G.; Giersch, W.; Schulte-Elte, K. H.; Enggist, P.;
Demole, E. Helv. Chim. Acta 1980, 63, 1582. (b) Sharpless,
K. B.; Michaelson, R. C. J. Am. Chem. Soc. 1973, 6136.
(9) Sheldon, R. A. In Aspects of Homogeneous Catalysis, Vol.
4; Ugo, E., Ed.; Reidel Publishing: Dordrecht, 1981, 3–70.
(10) (a) González, I. C.; Forsyth, C. J. J. Am. Chem. Soc. 2000,
122, 9099. (b) Hashimoto, M.; Kan, T.; Nozaki, K.;
Yanagiya, M.; Shirahama, H.; Matsumoto, T. J. Org. Chem.
1990, 55, 5088. (c) Corey, E. J.; Ha, D.-C. Tetrahedron Lett.
1988, 29, 3171.
7.49 (mc, J = 7.0 Hz, 1 H), 8.75 (s, 1 H), 10.23 (s, 1 H). 13
NMR (63 MHz, CDCl3): δ = 20.5, 22.6, 25.0, 25.8, 27.4,
C
36.0, 43.9, 61.2, 71.2, 83.0, 85.6, 110.9, 112.8, 118.0, 119.0,
121.4, 135.4, 156.7, 175.5. MS (EI, 70 eV,): m/z (%) = 314
+
+
(3) [M+], 171 (100) [C11H11N2 ], 143 (6) [C8H15O2 ], 84 (11)
(11) Hartung, J.; Greb, M. J. Organometal. Chem. 2002, 661, 67.
(12) Mimoun, H.; Mignard, M.; Brechot, P.; Saussine, L. J. Am.
Chem. Soc. 1986, 108, 3711.
[C5H8O+], 43 (10) [C3H6 ]. UV/Vis (EtOH): λmax (lg ε): 232
+
nm (3.76), 282 (3.81), 373 (2.46). C19H26N2O2 (314.4):
Calcd C, 72.58; H, 8.33; N, 8.91. Found: C, 67.25; H, 8.26;
N, 7.99. trans-1-[5-(1-Hydroxy-1-methylethyl)-2-
(13) Hartung, J.; Schmidt, P. Synlett 2000, 367.
(14) Hartung, J.; Drees, S.; Greb, M.; Schmidt, P.; Svoboda, I.;
Fuess, H.; Murso, A.; Stalke, D. Eur. J. Org. Chem.,
submitted.
(15) Weinert, B.; Wüst, M.; Mosandl, A.; Hanssum, H.
Phytochem. Anal. 1998, 9, 10.
(16) A solution of (3R)-linalool (2) (154 mg, 1.00 mmol) in
CHCl3 (5 mL) and vanadium(V) complex 4b (36.3 mg, 0.10
mmol) was stirred for 5 min at 25 °C. Subsequently, TBHP
(273 µL, 5.5 M in nonane, 1.50 mmol) was added and the
deep red reaction mixture was stirred for additional 12 h at
25 °C. Afterwards, the solvent was removed at 250 mbar/
40 °C to afford a dark brown residue which was filtered
through a short pad of Al2O3 in order to remove the catalyst.
The product was washed with Et2O (75 mL) from the
column. Combined filtrate and eluate were concentrated in
vacuo to provide an oil which was distilled under reduced
pressure. The distillate was purified by column
methyltetrahydrofuran-2-yl]-1,2,3,4-tetrahydro-9H-β-
carboline: colorless solid, mp 113 °C. [α]D25 –19.5 (c 0.63,
CHCl3). 1H NMR (250 MHz, CDCl3): δ = 1.08 (s, 3 H), 1.22
(s, 3 H), 1.40 (s, 3 H), 1.89–2.22 (m, 4 H), 2.68–2.90 (m, 2
H), 3.22 (ddd, J = 15.0, 9.8, 5.2 Hz, 2 H), 3.99 (dd, J = 8.2,
5.4 Hz, 1 H), 4.08–4.12 (m, 1 H), 7.05–7.20 (m, 2 H), 7.33
(mc, 1 H), 7.50 (mc, 1 H), 8.60 (s, 1 H). 13C NMR (63 MHz,
CDCl3): δ = 21.6, 22.6, 24.6, 26.1, 28.8, 36.8, 43.0, 60.6,
70.4, 77.0, 86.6, 110.1, 110.9, 118.0, 119.0, 121.5, 142.3,
153.4, 174.1. MS (EI, 70 eV): m/z (%) = 314(3) [M+],
+
+
171(100) [C11H11N2 ], 143(6) [C8H15O2 ], 84(11) [C5H8O+],
+
43(10) [C3H6 ]. UV/Vis (EtOH): λmax (lg ε): 242 nm (4.52),
282 (3.85), 371 (2.57). C19H22N2O2 (314.4): Calcd C, 72.58;
H, 8.33; N, 8.91. Found: C, 67.94; H, 8.06; N, 7.78.
(25) cis-1-[5-(1-Hydroxy-1-methylethyl)-2-methyltetrahydro-
furan-2-yl]-9H-β-carboline cis-3: colorless solid, mp
161 °C. [α]D25 –32.9 (c 0.57, CHCl3). 1H NMR (250 MHz,
CDCl3): δ = 1.23 (s, 3 H), 1.45 (s, 3 H), 1.78 (s, 3 H), 1.75–
3.08 (m, 4 H), 4.15 (t, J = 7.3 Hz, 1 H), 7.24 (ddd, J = 7.8,
6.1, 1.8 Hz, 1 H), 7.52 (mc, 2 H), 7.86 (d, J = 5.5 Hz, 1 H),
8.13 (d, J = 7.9 Hz, 1 H), 8.39 (d, J = 5.5 Hz, 1 H), 9.53 (s,
1 H). 13C NMR (63 MHz, CDCl3): δ = 24.2, 26.2, 27.6, 27.9,
37.3, 73.3, 88.4, 90.2, 111.5, 113.4, 119.7, 121.6, 121.7,
128.3, 133.2, 136.1, 138.0, 143.2, 148.0. MS (EI, 70 eV):
m/z (%) = 310(17) [M+], 151(24) [C16H15N2O+], 209 (100)
chromatography [SiO2, petroleum ether–Et2O–acetone,
5:2:1 (v/v/v); Rf cis-1 = 0.48; Rf trans-1 = 0.45] to provide
111 mg (65%) linalool oxide 1: colourless liquid, bp 80 °C/
10 mbar (Kugelrohr, Lit. 78 °C/13 Torr), cis:trans = 61:39.
cis-1: [α]D25 +29.1 (c 1.1, CHCl3), ref.17: [α]D25 +11.7
(c = 0.1, CH3OH). 1H NMR (250 MHz, CDCl3): δ = 1.11 (s,
3 H), 1.20 (s, 3 H), 1.29 (s, 3 H), 1.75–1.89 (m, 4 H), 2.05 (s
br, 1 H, OH), 3.84 (dd, J = 8, 7 Hz, 1 H), 4.97 (dd, J = 11, 2
Hz, 1 H), 5.17 (dd, J = 17, 2 Hz, 1 H), 5.96 (dd, J = 17, 11
25
Hz, 1 H). trans-1: [α]D25 –13.1 ( c 1.0, CHCl3), ref.17: [α]D
+
+
[C14H12N2 ], 182 (11) [C10H16NO2 ], 43 (9) [C2H4O+]. UV/
Vis (EtOH): λmax (lg ε): 242 nm (4.52), 288 (4.26), 348
(3.77). C19H22N2O2 (310.4): Calcd C, 73.52; H, 7.14; N,
–10.1 (c 0.1, CH3OH). 1H NMR (250 MHz, CDCl3):
δ = 1.10 (s, 3 H), 1.21 (s, 3 H), 1.29 (s, 3 H), 1.66–1.74 (mc,
1 H), 1.75–1.93 (m, 3 H), 2.05 (s, br., 1 H, OH), 3.78 (t, J = 7
Synlett 2003, No. 2, 223–226 ISSN 0936-5214 © Thieme Stuttgart · New York