A. J. F. Edmunds et al. / Bioorg. Med. Chem. Lett. 10 (2000) 1365±1368
1367
Scheme 2. Reagents and conditions: (a) R2OSO2Me, NaH, DMF, 0 ꢀC to rt; (b) R2OSO2Me, K2CO3, DMF, 50 ꢀC; (c) LiOH.H2O, MeOH:H2O
(4:1); (d) AD-mix-b, t-BuOH:H2O (1:1), 0 ꢀC to rt; (e) Ag2O, MeI, DMF, 50 ꢀC.
References and Notes
M. G.; Bissett, B. D.; Bui, C. T.; Pham, Ha T. T.; Simpson, G.
W. Aust. J. Chem. 1998, 51, 9.
13. As determined by gas chromatography analysis after ther-
modynamic equilibrium.
1. Isaac, B. G.; Ayer, S. W.; Elliott, R.; Stonard, R. J. J. Org.
Chem. 1992, 57, 7220.
2. Edmunds, A. J. F.; Trueb, W.; Oppolzer, W.; Cowley, P.
Tetrahedron 1997, 53, 2785.
3. Blakemore, P. R.; Kocienski, P. J.; Morley, A.; Muir, K. J.
Chem. Soc., Perkin Trans. 1 1999, 8, 955.
4. Syntheses of a diastereoisomer of herboxidiene, as well as
several partial syntheses, have been reported. See: (a). Smith,
N. D.; Kocienski, P. J.; Street, S. D. Synthesis 1996, 652. (b).
Banwell, M. G.; Bui, C. T.; Simpson, G. W. J. Chem. Soc.,
Perkin Trans. 1 1998, 4, 791. (c). Banwell, M. G.; Bui, C. T.;
Hockless, D. C. R.; Simpson, G. W. J. Chem. Soc., Perkin
Trans. 1 1997, 9, 1261. (d). Banwell, M. G.; Bui, C. T.;
Simpson G. W.; Watson, K. G. Chem. Commun. 1996, 723.
5. Koguchi, Y.; Nishio, M.; Kotera, J.; Omori, K.; Ohnuki, T.;
Komatsubara, S. J. Antibiot. 1997, 50, 970.
14. [(2R,6S)-6-(3-Hydroxy-phenyl)-tetrahydropyran-2-yl] ace-
tic acid methyl ester (11): 1H NMR (300 MHz, CDCl3):
1.32.54, m, 2H; 1.63.75, m, 2H; 1.82, m, 1H; 1.91.97, m, 1H;
2.50, dd ( J=15.3, 5.4 Hz), 1H; 2.68, dd (J=15.3, 7.5 Hz ), 1
H; 3.68, s, 3H; 3.93.02, m, 1H; 4.45, dd (J=11.4, 2.1 Hz), 1H;
6.20, br s, 1H; 6.69, dd (J=8.1, 2.4 Hz), 1H; 6.81, d (J=2.4
Hz), 1H; 6.84, d (J=8.1 Hz), 1H; 7.13 ppm, t (J=8.1 Hz), 1H.
13C NMR (75.4 MHz, CDCl3): 23.4 (t); 30.7 (t); 32.6 (t); 41.3
(t); 51.7 (q); 74.5 (d); 79.4 (d); 112.9 (d); 114.1 (d); 117.5 (d);
129.1 (d); 144.2; 155.8; 172.5 ppm. Electron Spray MS
(+Mode): 251 (MH+, 100%); 207(18%): 131 (35%); 93
(15%).
15. (a) Brown, H. C.; Chandrasekharan, J.; Ramachandran, P.
V. J. Am. Chem. Soc. 1988, 110, 1539. (b) Midland, M. M.;
McLoughlin, J. J. J. Org. Chem. 1984, 49, 1316.
6. Horiguchi, T.; Shirasaki, M.; Tanida, S. Takeda Kenkyush-
oho 1996, 55, 149.
16. Determined by HPLC analysis on a Chiracel OD-H col-
umn, eluting with 95:5 hexane:isopropyl alcohol.
7. Sauter, H.; Steglich, W.; Anke, T. Angew. Chem., Int. Ed.
Eng. 1999, 38, 1329.
17. The mesylates required for the preparation of compounds
12, 14 and 16 were prepared by treatment of the commercially
available alcohols with MeSO2Cl, Et3N, in CH2Cl2 according
to standard procedures. The mesylate required for preparation
of compound 15 was prepared as follows:
8. Edmunds, A. J. F.; Trueb, W. Tetrahedron Lett. 1997, 38, 1009.
9. The tert-butyldimethylsilane (TBDMS) group was chosen
as the protecting group to allow selective, mild deprotection at
the ®nal step in the syntheses. All attempts to directly add the
TBDMS-protected Grignard to cyclopentanone failed, reduced
Grignard being the only product obtained.
10. Royer, R.; Buisson, J. P.; Demerseman, P; Cheutin, A.,
Bull. Soc. Chim. Fr. 1970, 10, 3647. Use of BBr3 in CH2Cl2
even at low temperatures led to complex reaction mixtures.
11. Van Rheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron
Lett. 1976, 1973.
12. A mixture of the E and Z isomers can actually be used for
the ring closure step but it was more convenient to separate
isomers to simplify the GC analysis for this process. The eect
of double bond geometry on kinetic intramolecular Michael
addition reactions of this type has been reported. See; Banwell,
Reagents: (a) MeSO2Cl, Et3N, DMAP(cat.), CH2Cl2, 0 ꢀC to
rt (b) meta-Chlorperbenzoic acid, NaHCO3, CH2Cl2, rt.
18. Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B.
Chem. Rev. 1994, 94, 2483.
19. H NMR (300 MHz, CDCl3) for 18: 0.98, d (J=5.1 Hz),
3H; 1.18, s, 3H; 1.20, s, 3H; 1.10.05, m, 13H; 2.48, dd,
(J=15.8, 5.9 Hz), 1H; 2.68, dd (J=15.8, 6.9 Hz ), 1H; 2.90, dd,
1