4950
P. Magnus et al. / Tetrahedron Letters 42 (2001) 4947–4950
stein, M.; Maise, W. M. J. Antibiot. 2000, 53, 256.
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3. (a) Bauta, W. E.; Booth, J.; Bos, M. E.; DeLuca, M.;
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Magnus, P.; Mendoza, J.; Pye, P.; Tarrant, J. G.; Thom,
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der, P. A.; Rice, K. D.; Schnute, M. E. J. Am. Chem. Soc.
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Org. Chem. 1991, 56, 6267; (d) Wender, P. A.; Lee, H. Y.;
Wilhelm, R. S.; Williams, P. D. J. Am. Chem. Soc. 1989,
111, 8954; (e) Hendrickson, J. B.; Farina, J. S. J. Org.
Chem. 1980, 45, 3359; (f) Sammes, P. G.; Street, L. J. J.
Chem. Soc., Chem. Commun. 1983, 666; (g) Sammes, P.
G.; Street, L. J. J. Chem. Soc., Chem. Commun. 1982,
1056.
4. Carlson, R.; Nilsson, A.; Stro¨mqvist, M. Acta Chem.
Scand. Ser. B 1983, 37, 7.
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104, 4021; (b) Johnson, C. R.; Zeller, J. R. Tetrahedron
1984, 40, 1225.
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1352; (b) Comprehensive Organic Synthesis; Trost, B. M.;
Fleming, I., Ed.; Pergamon Press: Oxford, 1991; Vol. 6,
p. 1066.
7. While the absolute configuration of guanacastepene was
not reported in the original paper (Ref. 1) it appears that
it is most likely as shown for 1, and therefore corresponds
to (+)-8 (Dr. Jon Clardy is thanked for this information).
8. Magnus, P.; Booth, J.; Diorazio, L.; Donohoe, T.; Lynch,
V.; Magnus, N.; Mendoza, J.; Pye, P.; Tarrant, J. Tetra-
hedron 1996, 52, 14103.
Figure 2. View of 20 with labeled heteroatoms. Thermal
ellipsoids are scaled to 30% probability level. Hydrogen atoms
shown are drawn to an arbitrary scale.
Table 1. Reactions of 19 with various Me transfer
reagents (product ratios of 20:21:22)
Conditions
20
21
22
1. MeLi/LiBr (1.2 equiv.)/THF
−78°C
2. MeLi/MAD/hexane 25°C
3. MeMgCl (5 equiv.)/CuI
(5 equiv.)/THF 0°C
1
2
0
0
1
0
14
1
1
0
4. MeMgCl (10 equiv.)/CuI
(5 equiv.)/THF 0°C
0
1
5. Me2CuLi (3.0)/hexane −10°C
6. Me2CuLi (5.0)/THF 0°C
7. Me2Zn/Ni(acac)2(cat.)/LiBr/THF
25°C
1
0
1
7
3
1
1
0
1
8. Me2Zn/Ni(acac)2(1 equiv.)/LiBr/
THF 25°C
1
0
2
2
1
0
2
9. (a) Flemming, S.; Kabbara, J.; Nickisch, K.; Neh, H.;
Westermann, J. Synthesis 1995, 317; (b) Ashby, E. C.;
Heinsohn, G. J. Org. Chem. 1974, 39, 3297; (c) Bagnell,
L.; Jeffery, E. A.; Meisters, A.; Mole, T. Aust. J. Chem.
1975, 28, 801; (d) Jeffery, E. A.; Meisters, A.; Mole, T. J.
Organomet. Chem. 1974, 74, 365.
9. Me2Zn (10 equiv.)/Ni(acac)2
(10%)/THF 25°Ca
10. Me2Zn/LiBr/THF/25°C
11. Me3Al/THF 25°C
1
1
0
20
1
0
0
12. Me3Al (2 equiv.)/Ni(acac)2
8 (80%)
8 (82%)
20 (88%)
(10%)/THF 25°Cb
10. Spectral data 1H NMR data for key compounds: Com-
13. Me3Al (1.5 equiv.)/Ni(acac)2
(10%)/THF 25°C
14. Me3Al (1.5 equiv.)/Ni(acac)2
(10%)/THF 0°C
1
1
0
0
1
pound 12b: H NMR (300 MHz, CDCl3) l 7.89–7.85 (m,
2H), 7.65–7.53 (m, 3H), 5.91 (br s, 1H), 3.38–3.26 (m,
2H), 2.71 (s, 3H), 1.84–1.33 (m, 5H), 1.10 (q, J=9.0 Hz,
1H), 0.93 (s, 3H), 0.92 (s, 3H), 0.89 (d, J=6.6 Hz, 3H),
0.80 (d, J=6.6 Hz, 3H). Compound 8: 1H NMR (300
MHz, CDCl3) l 4.87 (d, J=0.9 Hz, 1H), 4.76 (d, J=1.5
Hz, 1H), 2.37–2.25 (m, 2H), 2.19–2.07 (m, 1H), 1.99–1.87
(m, 1H), 1.82–1.73 (m, 1H), 1.68–1.44 (m, 1H), 1.59 (s,
3H), 0.93 (d, J=6.6 Hz, 3H), 0.84 (d, J=6.6 Hz, 3H).
Compound 9: 1H NMR (300 MHz, CDCl3) l 9.76 (s,
1H), 4.81 (d, J=1.5 Hz, 1H), 4.65 (d, J=1.5 Hz, 1H),
2.38–2.22 (m, 2H), 2.00–1.86 (m, 1H), 1.68–1.20 (m, 3H),
1.61 (s, 3H), 0.94 (d, J=6.6 Hz, 3H), 0.82 (d, J=6.6 Hz,
a Me2Zn added over 2 h.
b Me3Al added over 30 min.
Acknowledgements
The Robert A. Welch Foundation, Merck Research
Laboratories and Novartis are thanked for their sup-
port of this research. The Swiss National Science Foun-
dation is also thanked for a post doctoral Fellowship
awarded to C.O.
1
3H). Compound 2: H NMR (300 MHz, CDCl3) l 7.22
(dd, J=9.6, 4.5 Hz, 1H), 5.97 (d, J=9.6 Hz, 1H), 4.85
(dd, J=7.2, 4.5 Hz, 1H), 2.78–2.62 (m, 1H), 2.36 (dd,
J=12.0, 7.2 Hz, 1H), 2.20–2.03 (m, 1H), 1.76–1.45 (m,
5H), 0.93 (d, J=6.3 Hz, 3H), 0.91 (d, J=6.3 Hz, 3H),
0.84 (s, 3H). Compound 20: 1H NMR (300 MHz, CDCl3)
l 4.36 (dd, J=6.0, 1.8 Hz, 1H), 2.77–2.41 (m, 4H),
2.08–1.97 (m, 2H), 1.84–1.73 (m, 1H), 1.65–1.35 (m, 3H),
1.59 (s, 3H), 0.98 (d, J=6.3 Hz, 3H), 0.91 (d, J=6.6 Hz,
3H), 0.89 (s, 3H).
References
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