H. Tanimoto et al. / Tetrahedron Letters 49 (2008) 358–362
361
250.1205, calcd for C14H18O4, M+, 250.1205. Anal. Calcd
for C14H18O4: C, 67.18; H, 7.25. Found: C, 67.28; H, 7.14.
Data of 5: syrup; ½aꢁD ꢀ54 (c 0.61, CHCl3); IR mmax (neat)
21st Century COE program ‘KEIO LCC’) for financial
assistance.
27
2940 and 1730 cmꢀ1; 1H NMR d 6.94 (dd, 1H, J = 8.1 and
8.1 Hz), 6.85 (dd, 1H, J = 8.1 and 2.1 Hz), 6.83 (dd, 1H,
J = 8.1 and 2.1 Hz), 6.13 (d, 1H, J = 10.5 Hz), 5.85 (ddd,
1H, J = 10.5, 3.3 and 3.3 Hz), 4.03 (q, 2H, J = 7.2 Hz),
3.92 (q, 2H, J = 7.2 Hz), 3.89 (s, 3H), 3.84 (s, 3H), 3.64 (d,
1H, J = 15.0 Hz), 2.89 (d, 1H, J = 15.0 Hz), 2.73 (dddd,
1H, J = 12.0, 5.4, 3.3 and 3.3 Hz), 2.09 (dd, 1H, J = 15.3
and 3.3 Hz), 1.91 (dd, 1H, J = 15.3 and 12.0 Hz), 1.77–
2.18 (m, 3H), 1.53 (dddd, 1H, J = 14.1, 5.4, 5.4 and
5.4 Hz), 1.18 (t, 3H, J = 7.2 Hz), 1.02 (t, 3H, J = 7.2 Hz);
13C NMR d 173.6, 171.8, 152.8, 148.1, 135.8, 132.5, 126.1,
122.6, 122.3, 111.38, 60.3, 60.0, 59.7, 55.7, 45.3, 44.6, 37.8,
35.3, 21.9, 21.2, 14.2, 14.0; HRMS (FAB) m/z 413.1932,
calcd for C22H30NaO6, (M+Na)+, 413.1940. Data of 20:
syrup; ½aꢁ2D4 +21 (c 0.54, CHCl3); IR mmax (neat) 2920, 2860,
1720 and 1500 cmꢀ1; 1H NMR d 9.55 (dd, 1H, J = 2.5 and
2.2 Hz), 6.74 (d, 1H, J = 8.0 Hz), 6.66 (d, 1H, J = 8.0 Hz),
6.42 (dd, 1H, J = 9.5 and0.8 Hz), 5.81 (dd, 1H, J = 9.5
and 5.9 Hz), 4.61 (d, 1H, J = 7.1 Hz), 3.90 (s, 3H), 3.43
(ddd, 1H, J = 11.9, 7.1 and 4.6 Hz), 2.64 (dd, 1H, J = 15.6
and 2.2 Hz), 2.52 (dd, 1H, J = 15.6 and 2.5 Hz), 2.51
(dddd, 1H, J = 11.5, 5.9, 4.4 and 0.8 Hz), 1.80 (dddd, 1H,
J = 13.7, 4.7, 4.4 and 2.5 Hz), 1.58 (m, 1H), 1.38 (dddd,
1H, J = 13.7, 13.4, 11.9 and 2.5 Hz), 0.85–1.01 (m, 1H),
0.96 (s, 9H), 0.12 (s, 3H), 0.03 (s, 3H); 13C NMR d 201.2,
145.5, 144.7, 130.0, 127.9, 123.7, 123.3, 117.9, 114.3, 97.6,
73.6, 56.8, 50.3, 44.8, 39.4, 29.6, 26.9, 25.8, 18.1, ꢀ4.6,
ꢀ5.0; LRMS (EI) m/z 400 (M+, 30), 356 (27), 343 (56), 299
(100). HRMS (EI) m/z 400.2074, calcd For C23H32O4Si,
M+, 400.2070. Data of 2: white crystals; mp 201–202 °C;
References and notes
1. For a review of morphine and related alkaloids, see: (a)
Kapoor, L. D. Opium Poppy: Botany, Chemistry and
Pharmacology; Food Products Press: New York, 1995; (b)
Butora, G.; Hudlicky, T.. In Organic Synthesis: Theory
and Applications; Hudlicky, T., Ed.; JAI Press: Stamford,
CT, 1998; Vol. 4, pp 1–51.
2. (a) Omori, A. T.; Finn, K. J.; Leisch, H.; Carroll, R. J.;
Hudlicky, T. Synlett 2007, 2859–2862; (b) Uchida, K.;
Yokoshima, S.; Kan, T.; Fukuyama, T. Org. Lett. 2006, 8,
5311–5313; (c) Parker, K. A.; Fokas, D. J. Org. Chem.
2006, 71, 449–455; (d) Trost, B. M.; Tang, W.; Toste, F.
D. J. Am. Chem. Soc. 2005, 127, 14785–14803; (e) Nagata,
H.; Miyazawa, N.; Ogasawara, K. Chem. Commun. 2001,
1094–1095; (f) Trauner, D.; Bats, J. W.; Werner, A.;
Mulzer, J. J. Org. Chem. 1998, 63, 5908–5918; (g) Mulzer,
J.; Bats, J. W.; List, B.; Opatz, T.; Trauner, D. Synlett
1997, 441–444; For reviews and other syntheses, see: (h)
Mascavage, L. M.; Wilson, M. L.; Dalton, D. R. Curr.
Org. Synth. 2006, 3, 99–120; (i) Zezula, J.; Hudlicky, T.
Synlett 2005, 388–405; (j) Novak, B. H.; Hudlicky, T.;
Reed, J. W.; Mulzer, J.; Trauner, D. Curr. Org. Chem.
2000, 4, 343–362.
3. Tanimoto, H.; Kato, T.; Chida, N. Tetrahedron Lett.
2007, 48, 6267–6270.
4. (a) Yamada, O.; Ogasawara, K. Org. Lett. 2000, 2, 2785–
2788; (b) Hanada, K.; Miyazawa, N.; Ogasawara, K. Org.
Lett. 2002, 4, 4515–4517.
5. Castro, A. M. M. Chem. Rev. 2004, 104, 2939–3002.
6. For reports of the successful cascade Claisen rearrange-
ment, see: (a) Curran, D. P.; Suh, Y.-G. Carbohydr. Res.
1987, 171, 161–191; (b) Tisdale, E. J.; Vong, B. G.; Li, H.;
Kim, S. H.; Chowdhury, C.; Theodorakis, E. A. Tetra-
hedron 2003, 59, 6873–6887.
7. (a) Ferrier, R. J.; Middleton, S. Chem. Rev. 1993, 93,
2779–2831; (b) Ferrier, R. J.; Middleton, S. Top. Curr.
Chem. 2001, 215, 277–291; (c) Chida, N.; Ohtsuka, M.;
Ogura, K.; Ogawa, S. Bull. Chem. Soc. Jpn. 1991, 64,
2118–2121.
28
28
½aꢁD ꢀ132 (c 0.32, CHCl3) {lit.18 mp 199–200 °C; ½aꢁD
ꢀ136 (c 2.55, CHCl3)}; IR mmax (neat) 3400, 2920, 2860,
1640, 1620 and 1500 cmꢀ1 1H NMR d 6.73 (d, 1H,
;
J = 8.3 Hz), 6.65 (d, 1H, J = 8.3 Hz), 4.38 (d, 1H,
J = 6.6 Hz), 3.87 (s, 3H), 3.44 (ddd, 1H, J = 12.4, 6.6
and 4.9 Hz), 3.28 (br s, 1H), 3.02 (d, 1H, J = 18.5 Hz),
2.70 (dd, 1H, J = 12.2 and 4.1 Hz), 2.52 (s, 1H), 2.49 (dd,
1H, J = 18.5 and 5.1 Hz), 2.40 (br d, 1H, J = 12.9 Hz),
2.28 (ddd, 1H, J = 12.4, 12.4 and 3.9 Hz), 2.01 (ddd, 1H,
J = 12.4, 12.4 and 4.1 Hz), 1.82 (dddd, 1H, J = 12.9, 4.9,
2.7 and 2.7 Hz), 1.74 (dd, 1H, J = 12.4 and 3.9 Hz), 1.61
(dddd, 1H, J = 12.9, 2.7, 2.7 and 2.7 Hz), 1.39 (dddd, 1H,
J = 12.9, 12.9, 12.4 and 2.7 Hz), 0.97 (dddd, 1H, J = 12.9,
12.9, 12.9 and 2.7 Hz); 13C NMR d 144.2, 143.9, 129.9,
125.2, 119.1, 113.8, 96.9, 73.1, 59.9, 56.5, 47.2, 42.8, 42.4,
41.8, 34.7, 29.8, 23.5, 20.5; LRMS (EI) m/z 301 (M+, 100),
286 (1). HRMS (EI) m/z 301.1677. Calcd For C18H23NO3,
M+, 301.1678.
8. Boulineau, F. P.; Wei, A. Carbohydr. Res. 2001, 334, 271–
279.
9. (a) Bolitt, V.; Mioskowski, C.; Lee, S.-G.; Falck, J. R. J.
Org. Chem. 1990, 55, 5812–5813; (b) France, C. J.;
McFarlane, I. M.; Newton, C. G.; Pitchen, P.; Webster,
M. Tetrahedron Lett. 1993, 34, 1635–1638.
14. Attempted Eschenmoser–Claisen rearrangement (N,N-
dimethylacetamide dimethylacetal, toluene, reflux) and
Ireland–Claisen rearrangement {(1) Ac2O, pyridine (2)
LHMDS then TMSCl/Et3N} of 6 produced no cascade
rearranged products.
10. All new compounds described in this Letter were charac-
terized by 300 MHz 1H NMR (in CDCl3), 75 MHz 13C
NMR (in CDCl3), IR, and mass spectrometric and/or
elemental analyses.
11. Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33,
6299–6302.
15. When the Claisen rearrangement was carried out in the
presence of 2-nitorophenol (53 mol %), the rearranged
product was obtained in a less satisfactory yield (53%).
16. The moderate yields of the cascade rearrangement and the
second rearrangement of the stepwise version were mainly
due to the decomposition of the substrates. The decom-
position would be induced by the formation of stabilized
conjugated carbocations generated from cyclohexenol
derivatives 6, 17 and/or 50 by elimination of water or
ethyl acetate under the acidic reaction conditions. For the
acid sensitivity of the structurally related cyclohexenol,
see: Chida, N.; Sugihara, K.; Amano, S.; Ogawa, S. J.
Chem. Soc., Perkin Trans. 1 1997, 275–280.
12. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
24:5
13. Data of 6: white crystals; ½aꢁD ꢀ41 (c 0.87, CHCl3); mp
110.5–111.5 °C; IR mmax (KBr) 3350, 2930 and 1580 cmꢀ1
;
1H NMR d 7.04 (dd, 1H, J = 12.0 and 12.0 Hz), 6.88 (d,
1H, J = 12.0 Hz), 6.80 (d, 1H, J = 12.0 Hz), 5.82 (ddd,
1H, J = 3.6, 3.6 and 1.8 Hz), 4.45 (m, 1H), 3.88 (s, 3H),
3.81 (s, 3H), 3.84 (m, 1H), 2.89 (d, 1H, J = 5.1 Hz), 2.59
(br, 1H), 2.30–2.36 (m, 2H), 2.08 (dddd, 1H, J = 12.9, 4.5,
4.5 and 4.2 Hz), 1.81 (m, 1H); 13C NMR d 152.5, 145.6,
137.7, 134.3, 128.5, 124.7, 122.4, 111.5, 74.5, 72.2, 60.9,
55.8, 27.4, 24.5; LRMS (EI) m/z 250 (M+, 29), 232 (83),
214 (100), 199 (64), 184 (43), 159 (39); HRMS (EI) m/z