make 17. The crude products (20) from each series (19f or 19s)
were identical, and the nitrogen protecting group could be then
be removed under non-acidic conditions (Bu4NF, THF) to
afford 21 (53% overall from 19f, 49% overall from 19s).
Compound 21, which was stable to silica gel flash chromatog-
raphy, now provided an opportunity to generate an imine that
would be expected to tautomerize spontaneously to 22. Several
methods are available for converting an amine into an imine,11
but the classical procedure11b of N-chlorination (t-BuOCl)12
and base treatment (DBU) proved satisfactory (71%), and took
the route as far as the pyridinone 22. From this point,
cladobotryal (1) was easily reached via the natural product 2 by
desilylation (Bu4NF, THF, 97%) and Dess–Martin oxidation (2
? 1, 97%). The 1H and 13C NMR spectra of our racemic
materials matched those reported for the natural products.
All new compounds except for 14 and 20, which were used
crude, were fully characterized by spectroscopic methods,
including high resolution mass spectrometry.
We thank NSERC and Crompton Co. (Elmira, Ontario) for
financial support. X.H. holds a Graduate Research Assistant-
ship.
Notes and references
1 J. Breinholt, H. C. Jensen, A. Kjær, C. E. Olsen, B. R. Rassing, C. N.
Rosendahl and I. Søtofte, Acta Chem. Scand., 1998, 52, 631–634.
2 S. Sakemi, J. Bordner, D. L. DeCosta, K. A. Dekker, H. Hirai, T.
Inagaki, Y.-J. Kim, N. Kojima, J. C. Sims, Y. Sugie, A. Sugiura, J. A.
Sutcliffe, K. Tachikawa, S. J. Truesdell, J. W. Wong, N. Yoshikawa and
Y. Kojima, J. Antibiot., 2002, 55, 6–18.
3 (a) T. Kappe, P. F. Fritz and E. Ziegler, Chem. Ber., 1973, 106,
1927–1942; (b) see also S. Goodwin, J. N. Shoolery and L. F. Johnson,
J. Am. Chem. Soc., 1959, 81, 3065–3069; (c) S. Goodwin, A. F. Smith,
A. A. Velasquez and E. C. Horning, J. Am. Chem. Soc., 1959, 81,
6209–6213.
4 E.g. 3,5-Dihydro-2H-furo[3,2-c]pyridin-4-one (the parent system): B.
A. J. Clark, M. S. El-Bakoush and J. Parrick, J. Chem. Soc., Perkin
Trans. 1, 1974, 1531–1536.
5 D. L. J. Clive and X. Huang, Tetrahedron, 2002, 58, 10243–10250.
6 S. Campestrini, F. Di Furia and G. Modena, J. Org. Chem., 1990, 55,
3658–3660.
7 (a) E. Testa, L. Fontanella, G. F. Cristiani and L. Mariani, Liebigs Ann.,
1961, 639, 166–180; (b) H. V. Secor and E. B. Sanders, J. Org. Chem.,
1978, 43, 2539–2541; (c) W. J. Gensler and S. K. Dheer, J. Org. Chem.,
1981, 46, 4051–4057.
8 (a) Y. Yuasa, N. Fujimaki, T. Yokomatsu, J. Ando and S. Shibuya, J.
Chem. Soc., Perkin Trans. 1, 1998, 3577–3584; (b) G. Guanti, E.
Narisano, T. Podgorski, S. Thea and A. Williams, Tetrahedron, 1990,
46, 7081–7090.
9 DDQ, PhH, reflux; Pd/C, xylene, reflux or PhOPh at 220 °C; MnO2,
xylene, reflux; DDQ, CF3CO2H, PhMe, 80 °C; (NH4)2Ce(NO3)6,
water–acetone or MeCN; (NH4)2Ce(NO3)6, 2,6-pyridinedicarboxylic
acid N-oxide, water–MeCN; Ph3CPF6, CH2Cl2; DDQ, Me3SiOSO2CF3,
PhH; [PhSe(O)]2O, PhMe, reflux.
10 (a) M. Sakaitani and Y. Ohfune, J. Org. Chem., 1990, 55, 870–876; (b)
P. A. Grieco and A. Perez-Medrano, Tetrahedron Lett., 1988, 29,
4225–4228; (c) F. Busqué, P. de March, M. Figueredo, J. Font, T.
Gallagher and S. Milán, Tetrahedron: Asymmetry, 2002, 13, 437–445;
(d) Cf. A. D. Brosius, L. E. Overman and L. Schwink, J. Am. Chem.
Soc., 1999, 121, 700–709.
11 (a) Cf. S. Dayagi and Y. Degani, in The Chemistry of the Carbon–
Nitrogen Double Bond, ed. S. Patai, Interscience, New York, 1970, pp.
117–120; (b) W. E. Bachmann, M. P. Cava and A. S. Dreiding, J. Am.
Chem. Soc., 1954, 76, 5554–5555; (c) M. P. Cava and B. R. Vogt,
Tetrahedron Lett., 1964, 2813–2816; (d) J. J. Cornejo, K. D. Larson and
G. D. Mendenhall, J. Org. Chem., 1985, 50, 5382–5383 and references
therein (e) Reviews: R. V. Hoffman, R. A. Bartsch and B. R. Cho, Acc.
Chem. Res., 1989, 22, 211–217; (f) S. Pawlenko, in Methoden der
Organischen Chemie (Houben-Weyl), Georg Thieme Verlag, Stuttgart,
1990, vol. E14b, pp. 226–233.
Scheme 3 (i) 3 equiv. LDA, THF, 278 °C, then room temp.; then add 12 in
THF–HMPA at 278 °C, 71%, recovery of 5 = 29%; (ii) DIBAL-H,
CH2Cl2, 278 °C, ca. 100% ; (iii) TsOH·pyridine, THF, 45 °C, 54% of 15f,
27% of 15s; (iv) Dess–Martin periodinane, CH2Cl2, 96% for 15f, 85% for
15s; (v) (a) (Me3Si)2NK, THF, 0 °C, then PhSeCl, 278 °C, (b) H2O2,
pyridine, CH2Cl2, 74% overall for 16f, 24% (not optimized) for 16s; (vi) i-
Pr3SiOSO2CF3, 2,6-lutidine, CH2Cl2, reflux, 100% for both 16f and 16s;
(vii) (a) (Me3Si)2NK, THF, 278 °C, PhSeCl, 278 °C, (b) H2O2, pyridine,
CH2Cl2; (viii) Bu4NF, THF, 0 °C, 53% overall for 16f, 49% for 16s; (ix) (a)
t-BuOCl, CH2Cl2, 278 °C, (b) DBU, PhMe, 71%; (x) Bu4NF, THF, 97%;
(xi) Dess–Martin, CH2Cl2, 97%.
12 (a) M. J. Mintz and C. Walling, Org. Synth., Coll. Vol. V, 1973,
184–187; (b) Hazard warning: Org. Synth., Coll. Vol. V, 1973, pp.
183–184.
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