Scheme 3 Reagents and conditions: i, NaOMe, MeOH; ii, MOM-Cl,
Pri2NEt, (CH2Cl)2 (92%); iii, Zn, AcOH, MeOH (91%); iv, NaHCO3, Ph2O,
reflux, 30 min (77% for 18; 96% for 22); v, sat. HCl–MeOH (100% for 2,
5, 6); vi, 4-NO2C6H4CO2H, DIAD, PPh3, THF (74%); vii, K2CO3, MeOH
(94%); viii, MOMCl, Pri2NEt, CH2Cl2 (97%); ix, Zn, AcOH, MeOH (99%);
x, MOMCl, Pri2NEt, CH2Cl2 (82%); xi, K2CO3, MeOH (94%); xii, PCC,
CH2Cl2 (94%); xiii, NaBH4–CeCl3 (93%).
Scheme 4 Reagents and conditions: i, OsO4 (cat.), NMO, aq. THF (97%);
ii, MOMCl, Pri2NEt, CH2Cl2 (95%); iii, Zn, AcOH, MeOH (91%); iv,
NaHCO3, Ph2O, reflux, 30 min (93%) (90% for 29); v, sat. HCl–MeOH
(100% for 1 and 4); vi, OsO4 (cat.), NMO, aq. THF (97%); vii, BnBr, NaH,
reflux, 30 min, Bu4NI, THF (97%); viii, Zn, AcOH, MeOH (98%); ix,
NaHCO3, Ph2O, (90%); x, OsO4 (cat.), NMO, aq. THF; xi, MOMCl,
Pri2NEt, CH2Cl2 (96%); xii, H2, Pd(OH)2, MeOH (93%); xiii, Im2CNS,
toluene (94%); xiv, (MeO)3P, reflux (97%).
On the other hand, the trans-diol 12 was first transformed
into the di-MOM ether 20, [a]3D0 273.6 (c 1.01, CHCl3), which
was further transformed into the tricyclic alcohol 21, [a]3D1 28.0
(c 1.04, CHCl3), by sequential reductive cleavage, MOM
protection and debenzoylation. Themolysis of 21 afforded the
cyclohexenol 22, [a]D28 +24.5 (c 1.01, CHCl3), which was
epimerized to 24, [a]D29 +142.1 (c 1.03, CHCl3), via the
cyclohexenone 23, [a]3D0 +41.4 (c 1.05, CHCl3), by oxidation
followed by diastereoselective 1,2-reduction in the presence of
cerium(iii) chloride.10 Compound 24 afforded (+)-conduritol B
2, mp 174–175 °C, [a]D28 +153.5 (c 0.31, MeOH) [lit.2c mp
174–175 °C, [a]2D0 2179 (c 1.2, MeOH)], on MOM deprotec-
tion (Scheme 3).
Although enantiocontrol is not required for the construction
of the two remaining conduritols, A 1 and D 4, having meso
structures, the same intermediate 8 was used as the starting
material to demonstrate the potential of our building block.
Thus, 8 was first transformed into the tri-MOM ether 25, [a]D26
233.0 (c 1.01, CHCl3), which was then converted to the
cyclohexenol 27, [a]2D5 28.7 (c 1.11, CHCl3), by sequential
MOM protection, reductive cleavage and thermolysis. Com-
pound 27 afforded conduritol A 1, mp 141–142 °C (lit.,2a mp
140–141 °C), on MOM deprotection.
Compound 8, on the other hand, was first transformed into
the dibenzyl ether 28, mp 91–92 °C, [a]2D9 263.1 (c 1.32,
CHCl3), which, on sequential reductive cleavage and thermol-
ysis, gave the cyclohexenol 29, [a]2D7 +12.8 (c 1.05, CHCl3). On
sequential diastereoselective dihydroxylation, MOM protec-
tion, debenzylation and thiocarbonylation, 29 furnished the
meso cyclohexane 30. Refluxing 30 with trimethyl phos-
phite11,12 allowed smooth dethiocarbodioxylation to give the
cyclohexene 31 which afforded conduritol D 42b on MOM
deprotection (Scheme 4).
In conclusion, the present synthesis provides the first
integrated route to all possible conduritol diastereomers with
complete diastereocontrol starting from a single chiral building
block by using MOM ether as the common protecting group.
Notes and references
† Satisfactory analytical (combustion and/or high resolution mass) and
1
spectroscopic (IR, H and 13C NMR, MS) data were obtained for isolable
new compounds.
1 Pertinent reviews, see: M. Balci, Y. Sütbeyaz and H. Seçen, Tetra-
hedron, 1990, 46, 3715; P. Vogel, D. Fattori, F. Gasparini and C. Le
Drian, Synlett, 1990, 173; H. A. J. Carless, Tetrahedron: Asymmetry,
1992, 3, 795; M. Balci, Pure Appl. Chem., 1997, 69, 97.
2 Some recent examples, see: (a) Y. Sütbeyaz, H. Seçen and M. Balci,
J. Chem. Soc., Chem. Commun., 1988, 1330 (A); (b) H. A. J. Carless and
O.Z. Oak, Tetrahedron Lett., 1989, 30, 1719 (A and D); (c) C. Le Drian,
J. P. Vionnet and P. Vogel, Helv. Chim. Acta, 1990, 73, 161 (B and F);
(d) B. M. Trost and E. J. Hembre, Tetrahedron Lett., 1999, 40, 219 (B);
(e) S. Takano, M. Moriya, Y. Higashi and K. Ogasawara, J. Chem. Soc.,
Chem. Commun., 1993, 177 (C); (f) H. Yoshizaki and J.-E. Bäckvall,
J. Org. Chem., 1998, 63, 9339 (C); (g) T. Yoshimitsu and K. Ogasawara,
Synlett, 1995, 257 (E and F).
3 S. Takano, Y. Higashi, T. Kamikubo, M. Moriya and K. Ogasawara,
Synthesis, 1993, 948; H. Konno and K. Ogasawara, Synthesis, 1999,
1135.
4 K. Ogasawara, Pure Appl. Chem., 1994, 66, 2119: K. Ogasawara,
J. Synth. Org. Chem. Jpn., in the press.
5 O. Mitsunobu, Synthesis, 1981, 1.
6 M. Prystas, H. Gustafsson and F. Sorm, Collect. Czech. Chem.
Commun., 1971, 36, 1487.
7 T. Kamikubo and K. Ogasawara, J. Chem. Soc., Chem. Commun., 1995,
1951.
8 T. Kamikubo and K. Ogasawara, Chem. Lett., 1996, 987.
9 S. F. Martin and J. A. Dodge, Tetrahedron Lett., 1991, 32, 3017.
10 A. L. Gemal and J. L. Luche, J. Am. Chem. Soc., 1981, 103, 5454.
11 E. J. Corey and R. A. E. Winter, J. Am. Chem. Soc., 1963, 85, 2677.
12 T. L. Nagabhushan, Can. J. Chem., 1970, 48, 383.
Communication 9/05462F
1986
Chem. Commun., 1999, 1985–1986