our laboratory, with bis(acetoxy)iodobenzene; this improved the
yield of oxidation up to 94%. Finally, according to Trost’s
synthesis6b 18 was subjected to Corey’s conditions13 using NaCN,
MnO2, and AcOH in MeOH at ambient temperature to give (+)-
juvabione (4), [a]D28 = +69.1 (c 1.00, benzene) [lit.:6g [a]D25 = +66.9
(c 2.57, benzene)], in 78% yield and complete the synthesis
(Scheme 4).
In conclusion, we have described the efficient synthesis of (+)-
juvabione (4) with excellent stereocontrol from the s-symmetric
keto-aldehyde 1 based on ‘‘asymmetric aldolisation/Norrish I
cleavage’’ methodology, in which the temporarily generated chiral
aldol motif in 2 plays essential roles in stereochemical control. The
present strategy is complementary to the aldolisation/retro-
aldolisation interconversion that we established3 and offers a
versatile use of 2 as a chiral cyclohexanoid block.
Scheme 3 Reagents and conditions: a) MeLi, CuI, THF, 240 uC, 1.5 h;
b) LiBF4, 1,4-dioxane, H2O, 50–70 uC, 7 h; c) TESCl, imidazole, DMF, rt,
12 h; d) hn (300 nm), MeOH, rt, 1.5 h.
Notes and references
1 Review: Catalytic Asymmetric Synthesis, ed. I. Ojima, Wiley-VCH, New
York, 2000.
2 N. Itagaki, M. Kimura, T. Sugahara and Y. Iwabuchi, Org. Lett., 2005,
7, 4185.
3 N. Itagaki, T. Sugahara and Y. Iwabuchi, Org. Lett., 2005, 7, 4181.
4 D. S. Weiss, in Organic Photochemistry, ed. A. Padwa, Marcel Dekker,
New York, 1981, vol. 5, p. 347.
5 For a pertinent review, see: C. H. Heathcock, S. L. Graham,
M. C. Pirring, F. Plavac and C. T. White, in Total Synthesis of
Natural Products, ed. J. ApSimon, Wiley, New York, 1983, vol. 5, p. 1.
6 For an asymmetric total synthesis of (+)-juvabione, see: (a) B. A. Pawson,
H.-C. Cheung, S. Gurbaxani and G. Saucy, J. Am. Chem. Soc., 1970,
92, 336; (b) B. M. Trost and Y. Tamaru, J. Am. Chem. Soc., 1977, 99,
3101; (c) E. Nagano and K. Mori, Biosci., Biotechnol., Biochem., 1992,
56, 1589; (d) H. Watanabe, H. Shimizu and K. Mori, Synthesis, 1994,
1249; (e) M. Kawamura and K. Ogasawara, J. Chem. Soc., Chem.
Commun., 1995, 2403; (f) H. Nagata, T. Taniguchi, M. Kawamura and
K. Ogasawara, Tetrahedron Lett., 1999, 40, 4207; (g) E. J. Bergner and
G. Helmchen, J. Org. Chem., 2000, 65, 5072. For an asymmetric formal
synthesis of (+)-juvabione, see: (h) W. H. Miles and H. R. Brinkman,
Tetrahedron Lett., 1992, 33, 589. For an asymmetric total synthesis of
(2)-juvabione, see: (i) C. Fuganti and S. Serra, J. Chem. Soc., Perkin
Trans. 1, 2000, 97; (j) A. A. Craveiro and I. G. P. Vieira, J. Braz. Chem.
Soc., 1992, 124; (k) G. Farges and H. Veschambre, Bull. Soc. Chim. Fr.,
1973, 11, 3172. For recent examples of racemic synthesis of juvabione,
see: (l) N. Soldermann, J. Velker, O. Vallat, H. S. Evans and R. Neier,
Helv. Chim. Acta, 2000, 83, 2266; (m) M. He, S. Tanimori and
M. Nakayama, Biosci., Biotechnol., Biochem., 1995, 59, 900.
7 The use of the MOM group in (+)-7 was essential for stability under
IBX-mediated oxidation conditions. However, the deprotection of the
MOM group in an advanced intermediate derived from 12 under several
acidic conditions failed. Thus, we converted the MOM ether to TES
ether before the photochemical cleavage.
8 For a detailed mechanistic consideration of the Norrish I reaction of
related bicyclo[3.3.1]nonan-2-one, see: R. O. Duthaler, R. S. Stingelin-
Schmid and C. Ganter, Helv. Chim. Acta, 1976, 59, 307.
9 T. Imamoto, N. Takiyama, K. Nakamura, T. Hatajima and Y. Kamiya,
J. Am. Chem. Soc., 1989, 111, 4392.
10 In the absence of CeCl3, the reaction of 12 and i-BuMgBr gave the
desired secondary alcohol (77%) together with an undesired primary
alcohol (8%) by hydride reduction and the starting aldehyde 12 was
recovered (15%).
11 D. B. Dess and J. C. Martin, J. Org. Chem., 1983, 48, 4155.
12 M. Shibuya, M. Tomizawa, I. Suzuki and Y. Iwabuchi, J. Am. Chem.
Soc., 2006, 128, 8412.
Scheme 4 Reagents and conditions: a) i-BuMgBr, CeCl3, THF, 0 uC, 2 h;
b) BOMCl, i-Pr2NEt, TBAI, THF, rt, 47 h; c) TBAF, THF, rt, overnight;
d) MnO2, CH2Cl2, rt, 12 h; e) (methoxymethyl)triphenylphosphonium
chloride, n-BuLi, THF, 230 uC, 2 h; f) 10% aq. HCl, THF, rt, 2 days; g)
Dess–Martin periodinane, CH2Cl2, rt, 1 h or cat. 1-Me-AZADO (19),
BAIB, CH2Cl2, rt, 7.5 h; h) NaCN, MnO2, AcOH, MeOH, rt, 24 h.
protection, TBAF-mediated removal of the TES group, and
MnO2 oxidation, 14 furnished the enone 15 in 92% yield. The
crucial C-1 homologation of the enone 15 was attained via the
Wittig reaction using (methoxymethyl)triphenylphosphonium
chloride and n-BuLi in THF at 230 uC to give the methyl dienol
ether 16, which was immediately treated with aqueous 10% HCl at
ambient temperature for 2 days to give the corresponding
hydroxy-a,b-unsaturated aldehyde 17 in 64% yield. While the
oxidation of resultant secondary alcohol 17 was carried out with
Dess–Martin periodinane11 to give the penultimate ketone 186a,6b
in 85% yield, it was found that using 5 mol% 1-methyl-2-
azaadamantane N-oxyl [1-Me-AZADO (19)],12 a stable nitroxyl-
radical-type oxidation catalyst that has recently been developed by
13 E. J. Corey, N. W. Gilman and B. E. Ganem, J. Am. Chem. Soc., 1968,
90, 5616.
1176 | Chem. Commun., 2007, 1175–1176
This journal is ß The Royal Society of Chemistry 2007