5818
K. Takao et al. / Tetrahedron Letters 46 (2005) 5815–5818
(br, 2H, OH), 2.66 (m, 1H), 3.78 (dd, 1H, J = 4.6,
References and notes
11.2 Hz), 3.88 (dd, 1H, J = 8.3, 11.2 Hz), 4.09 (dd, 1H,
J = 1.5, 7.5 Hz); 13C NMR d 22.3, 28.8, 32.2, 35.4, 37.9,
63.3, 76.5; HRMS calcd for C7H13O2 (M+ꢁH) m/z
129.0916, found 129.0916; HPLC analysis (column, Daicel
Chiralcel OD-H, EtOH–hexane = 1:20, flow rate =
0.7 mL/min); tR(min) = 15.3 for the mono-tosylate of
(1R,4S)-isomer, 17.1 for the mono-tosylate of (1S,4R)-
isomer. Compound cis-9 was determined to be 98% ee.
14. Partial racemization occurred under the basic Baeyer–
Villiger reaction conditions for 11. The enantiomeric
excess of thus obtained 12 was determined to be 83% by
chiral HPLC analysis.
1. (a) Pulici, M.; Sugawara, F.; Koshino, H.; Uzawa, J.;
Yoshida, S.; Lobkovsky, E.; Clardy, J. J. Org. Chem.
1996, 61, 2122–2124; (b) Pulici, M.; Sugawara, F.;
Koshino, H.; Okada, G.; Esumi, Y.; Uzawa, J.; Yoshida,
S. Phytochemistry 1997, 46, 313–319.
2. (a) Johnston, D.; McCusker, C. M.; Procter, D. J.
Tetrahedron Lett. 1999, 40, 4913–4916; (b) Johnston, D.;
McCusker, C. F.; Muir, K.; Procter, D. J. J. Chem. Soc.,
Perkin Trans. 1 2000, 681–695; (c) Johnston, D.; Francon,
N.; Edmonds, D. J.; Procter, D. J. Org. Lett. 2001, 3,
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2001–2004; (d) Johnston, D.; Couche, E.; Edmonds, D. J.;
15. Mulzer, J.; Graske, K.-D.; Shanyoor, M. Liebigs Ann.
1995, 593–598.
16. Oppolzer, W.; Poli, G.; Starkemann, C.; Bernardinelli, G.
Tetrahedron Lett. 1988, 29, 3559–3562.
Muir, K. W.; Procter, D. J. Org. Biomol. Chem. 2003, 1,
328–337; (e) Edmonds, D. J.; Muir, K. W.; Procter, D. J.
J. Org. Chem. 2003, 68, 3190–3198.
`
3. (a) Paquette, L. A.; Cuniere, N. Org. Lett. 2002, 4, 1927–
17. It is likely that a steric repulsion occurring between the
benzyl group in the EvansÕ auxiliary and the bis(OTMS)
groups makes its s-trans conformation unfavorable.
18. When the unprotected tosylate 17 was treated with KCN
in hot dimethyl sulfoxide, a ring-opening reaction involv-
ing elimination of the tosyl group occurred, forming an
acyclic product.
1929; (b) Paquette, L. A.; Kang, H.-J. Tetrahedron 2004,
60, 1353–1358.
4. For a review on the synthesis of optically active cyclo-
butane derivatives, see: (a) Lee-Ruff, E.; Mladenova, G.
Chem. Rev. 2003, 103, 1449–1483; For a review on the
application of cyclobutane derivatives in organic synthe-
sis, see: (b) Namyslo, J. C.; Kaufmann, D. E. Chem. Rev.
2003, 103, 1485–1537.
5. For recent reports on asymmetric synthesis of cyclobu-
tanes, see: (a) Villeneuve, K.; Tam, W. Angew. Chem., Int.
Ed. 2004, 43, 610–613; (b) Takasu, K.; Nagao, S.; Ueno,
M.; Ihara, M. Tetrahedron 2004, 60, 2071–2078; (c) Ito,
H.; Hasegawa, M.; Takenaka, Y.; Kobayashi, T.; Iguchi,
K. J. Am. Chem. Soc. 2004, 126, 4520–4521.
19. Compound 3 was obtained as a colorless oil: TLC Rf 0.53
24
(EtOAc–hexane, 1:2); ½aꢀD ꢁ119 (c 1.41, CHCl3); IR 2960,
1780 cmꢁ1; 1H NMR d 1.05 (s, 3H), 1.21 (s, 3H), 1.58 (dd,
1H, J = 7.0, 12.1 Hz), 2.06 (dddd, 1H, J = 0.7, 2.6, 9.0,
12.1 Hz), 2.39 (dd, 1H, J = 1.8, 18.3 Hz), 2.65 (ddd, 1H,
J = 0.7, 9.2, 18.3 Hz), 3.07 (m, 1H), 4.50 (dd, 1H, J = 2.6,
5.9 Hz); 13C NMR d 22.4, 26.8, 28.2, 35.1, 38.8, 38.8, 86.3,
178.6; HRMS calcd for C8H12O2 (M+) m/z 140.0837,
found 140.0838.
6. (a) Quendo, A.; Rousseau, G. Tetrahedron Lett. 1988, 29,
6443–6446; (b) Mitani, M.; Sudoh, T.; Koyama, K. Bull.
Chem. Soc. Jpn. 1995, 68, 1683–1687; (c) Miesch, M.;
Wendling, F. Eur. J. Org. Chem. 2000, 3381–3392.
20. Bick, S.; Zimmermann, S.; Meuer, H.; Sheldrick, W. S.;
Welzel, P. Tetrahedron 1993, 49, 2457–2468.
21. Tabusa, F.; Yamada, T.; Suzuki, K.; Mukaiyama, T.
Chem. Lett. 1984, 405–408.
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7. Fonquerna, S.; Moyano, A.; Pericas, M. A.; Riera, A.
Tetrahedron: Asymmetry 1997, 8, 1685–1691.
8. (a) Ainsworth, C.; Kuo, Y.-N. J. Organometal. Chem.
1972, 46, 73–87; (b) Schulz, W. J., Jr.; Speier, J. L.
Synthesis 1989, 163–166.
9. All new compounds were fully characterized by spectro-
scopic means (1H and 13C NMR, IR) and gave satisfactory
HRMS. Yields refer to homogeneous samples purified by
chromatography on silica gel.
10. Oppolzer, W.; Poli, G. Tetrahedron Lett. 1986, 27, 4717–4720.
11. For the synthesis of racemic trans-9 and cis-9, see:
Ramnauth, J.; Lee-Ruff, E. Can. J. Chem. 2001, 79, 114–
120.
12. Among two diastereomers trans-9 and cis-9, the less polar
compound was able to be converted into the bicyclic
lactone 3 (see Scheme 5). Accordingly, the less polar
isomer was determined to be cis-9.
22. The stereochemistry of the newly introduced stereogenic
center in 22 was determined by chemical transformation.
23. Compound 4 was obtained as a colorless oil: TLC Rf 0.65
24
(EtOAc–hexane, 1:2); ½aꢀD +83.4 (c 1.23, CHCl3); IR
2940, 1730 cmꢁ1 1H NMR d 1.03 (s, 9H), 1.74 (d, 3H,
;
J = 1.0 Hz), 2.32 (t, 2H, J = 6.5 Hz), 3.37 (s, 3H), 3.76 (t,
2H, J = 6.5 Hz), 4.39 (dd, 1H, J = 1.5, 8.6 Hz), 5.08 (dq,
1H, J = 8.6, 1.0 Hz), 7.35–7.47 (m, 6H), 7.62–7.66 (m,
4H), 9.46 (d, 1H, J = 1.5 Hz); 13C NMR d 17.6, 19.1,
26.8 · 3, 42.7, 56.7, 62.2, 83.4, 118.7, 127.7 · 4, 129.6 · 2,
133.7 · 2, 135.5 · 4, 143.0, 198.6; HRMS calcd for
C20H23O3Si (M+ꢁt-C4H9) m/z 339.1417, found 339.1415.
24. With LDA as a base, the combined yield of the aldol
adducts diminished to 36% (2–epimer = 2.3:1).
25. Compound 2 was obtained as a colorless oil: TLC Rf 0.45
23
(EtOAc–hexane, 1:3); ½aꢀD ꢁ59.0 (c 1.08, CHCl3); IR
13. Compound trans-9 was obtained as a colorless oil: TLC Rf
1
3490, 2930, 1770 cmꢁ1; H NMR d 0.98 (s, 3H), 1.03 (s,
22
0.38 (acetone–toluene, 1:1); ½aꢀD ꢁ10.3 (c 0.540, CHCl3);
IR 3350, 2960 cmꢁ1; 1H NMR d 1.06 (t, 1H, J = 10.1 Hz),
1.07 (s, 3H), 1.19 (s, 3H), 1.59 (t, 1H, J = 10.1 Hz), 2.29
(m, 1H), 2.44–2.60 (br, 2H, OH), 3.62 (dd, 1H, J = 7.5,
10.8 Hz), 3.63 (d, 1H, J = 8.4 Hz), 3.71 (dd, 1H, J = 5.3,
10.8 Hz); 13C NMR d 20.9, 28.2, 30.0, 38.3, 43.2, 65.4,
77.1; HRMS calcd for C7H13O2 (M+ꢁH) m/z 129.0916,
found 129.0913; HPLC analysis (column, Daicel Chiralcel
OD-H, EtOH–hexane = 1:40, flow rate = 0.7 mL/min);
tR(min) = 36.3 for the mono-tosylate of (1S,4S)-isomer,
38.9 for the mono-tosylate of (1R,4R)-isomer. Compound
trans-9 was determined to be 98% ee. Compound cis-9 was
obtained as a colorless oil: TLC Rf 0.56 (acetone–toluene,
9H), 1.16 (s, 3H), 1.40 (dd, 1H, J = 7.3, 12.1 Hz), 1.88 (d,
3H, J = 1.0 Hz), 1.90 (ddd, 1H, J = 2.9, 8.4, 12.1 Hz), 2.32
(t, 2H, J = 6.3 Hz), 2.41 (br s, 1H), 2.91 (m, 1H), 3.06 (br,
1H, OH), 3.25 (s, 3H), 3.56 (dd, 1H, J = 1.8, 9.2 Hz),
3.75–3.80 (m, 2H), 4.29 (t, 1H, J = 9.2 Hz), 4.46 (dd, 1H,
J = 2.9, 5.5 Hz), 4.94 (m, 1H), 7.35–7.47 (m, 6H), 7.62–
7.67 (m, 4H); 13C NMR d 17.3, 19.1, 22.4, 26.5, 26.8 · 3,
34.9, 38.3, 38.6, 42.9, 48.8, 55.7, 62.2, 76.1, 77.7, 86.4,
122.2, 127.7 · 4, 129.6 · 2, 133.8 · 2, 135.5 · 4, 142.6,
178.2; HRMS calcd for C28H35O5Si (M+ꢁt-C4H9) m/z
479.2254, found 479.2256.
26. The enantiomer of 2 would be synthesized from (1R)-
camphorsultam (in place of the 1S-isomer) and L-glycer-
aldehyde acetonide (in place of 20) in the same reaction
sequence.
24
1:1); ½aꢀD +29.0 (c 1.27, CHCl3); IR 3360, 2950 cmꢁ1; H
NMR d 1.08 (s, 3H), 1.12 (s, 3H), 1.60 (dd, 1H, J = 7.7,
11.2 Hz), 1.65 (ddd, 1H, J = 1.5, 8.6, 11.2 Hz), 2.09–2.23
1