Scheme 1. Retrosynthesis for the ABCD Fragment of
Spongistatin 1
Scheme 2. Synthesis of Alkyne 8
a Conditions: (a) TrCl, pyr, CH2Cl2, 16 h, rt; (b) (i) LiAlH4,
THF, 0 °C, 2 h, (ii) (COCl)2, DMSO, CH2Cl2, -78 °C then DIPEA
-78 f 0 °C; (c) HS(CH2)3SH, BF3‚Et2O, THF, -78 °C, 4 h; (d)
TBS-Cl, THF, imid, 2 h, rt; (e) n-BuLi, THF, rt, 10 min then (S)-
epichlorohydrin, THF, -20 °C f rt, 16 h; (f) (i) n-BuLi, THF,
-78 °C, 1 h, (ii) BF3‚THF, -78 °C, 1 h, (iii) epoxide, THF, -78
°C, 1.5 h; (g) I2, MeCN, NaHCO3, 0 °C; (h) TES-Cl, THF, imid,
2 h, rt; (i) Petasis reagent, microwave;12 (j) TBAF, THF, rt, 4 h;
(k) TES-Cl, THF, imid, 2 h, rt.
TIPS-protected acetylene was essential for the success of
this reaction; however, it was not possible to remove this
group in the presence of the other silicon functionality.
Therefore, global deprotection and reprotection as the bis-
TES ether afforded the desired alkyne 8.
The synthesis of aldehyde 9 began with dithiane 15.8 This
dithiane is also common to the synthesis of the CD fragment
(Scheme 3). Lithiation of dithiane 158 and interception of
the anion with epoxide 16 forms 17 in 91% yield. Cleavage
of the dithiane group with iodine- and borane-mediated syn-
Acena, J. L.; Bach, J.; Gibson, K. R.; Keown, L. E.; Oballa, R. M.;
Trieselmann, T.; Wallace, D. J.; Hodgson, A. P.; Norcross, R. D. Angew.
Chem., Int. Ed. 2001, 40, 4055. (e) Crimmins, M. T.; Katz, J. D.; Washburn,
D. G.; Allwein, S. P.; McAtee, L. F. J. Am. Chem. Soc. 2002, 124, 5661.
(f) Heathcock, C. H.; McLaughlin, M.; Medina, J.; Hubbs, J. L.; Wallace,
G. A.; Scott, R.; Claffey, M. M.; Hayes, C. J.; Ott, G. R. J. Am. Chem.
Soc. 2003, 125, 12844. For other ABCD syntheses, see: Terauchi, T.;
Terauchi, T.; Sato, I.; Shoji, W.; Tsukada, T.; Tsumoda, T.; Kanoh, N.;
Nakata, M. Tetrahedron Lett. 2003, 44, 7741. Zuev, D.; Paquette, L. A.
Org. Lett. 2000, 2, 679 for ABCD fragment syntheses.
(3) Pettit, G. R. J. Nat. Prod. 1996, 59, 812.
(4) Fernandez-Megia, E.; Gourlaouen, N.; Ley, S. V.; Rowlands, G. J.
Synlett 1998, 991.
(5) Gaunt, M. J.; Sneddon, H. F.; Orsini, P.; Hewitt, P.; Hook, D. F.;
Ley, S. V. Org. Biolmol. Chem. 2003, 1, 15; Sneddon, H. F.; Gaunt, M. J.;
Ley, S. V. Org. Lett. 2003, 5, 1147
(6) Mancuso, A. J.; Huang, S. L.; Swern, D. J. Org. Chem. 1978, 43,
2480.
(7) Ide, M.; Nakata, M Bull. Chem. Soc. Jpn., 1999, 72, 2491.
(8) Evans, A. B.; Knight, D. W. Tetrahedron Lett. 2001, 42, 6947.
(9) Based on Russell, G. A.; Ochrymowycz, L. A. J. Org. Chem. 1969,
34, 3618.
(10) Petasis, N. A.; Bzowej, E. I. J. Am. Chem. Soc. 1990, 112, 6392.
(11) Microwave-Accelerated Petasis Olefination. The Petasis reagent
(3.6 mL of a 0.2 M solution in toluene) was added to ketone 13 (250 mg,
0.45 mmol) and the ionic liquid 1-ethyl-3-methylimidazoline hexafluoro-
phosphate (40 mg), and the reaction was stirred at 160 °C for 10 min in a
Personal Chemistry Emrys Liberator Microwave. A fully automated coherent
synthesis system microwave machine was used. This was supplied by
Personal Chemistry, Hamnesplanaden 5, 75319, Uppsala, Sweden, www.
personalchemistry.com. Further studies on a microwave-accelerated Petasis
olefination will be published in due course.
Interestingly, the reaction proved to be much more efficient
when carried out under microwave heating, forming the
alkene 14 after 10 min in an improved 82% yield.11 The
(2) Evans, D. A.; Trotter, B. W.; Coleman, P. J.; Cote, B.; Dias, L. C.;
Rajapaske, H. A.; Tyler, A. N. Tetrahedron 1999, 55, 8671. Evans, D. A.;
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Evans, D. A.; Trotter, B. W.; Cote, B.; Coleman, P. J. Angew. Chem., Int.
Ed. Engl. 1997, 36, 2741. Evans, D. A.; Trotter, B. W.; Cote, B.; Coleman,
P. J.; Dias, L. C.; Tyler, A. N. Angew. Chem., Int. Ed. Engl. 1997, 36,
2744. (b) Guo, J. Duffy, K. J.; Stevens, K. L.; Dalko, P. I.; Roth, R. M.;
Hayward, M. M.; Kishi, Y. Angew. Chem., Int. Ed. 1998, 37, 187. Hayward,
M. M.; Roth, R. M.; Duffy, K. J.; Dalko, P. I.; Stevens, K. L.; Guo, J.;
Kishi, Y. Angew. Chem., Int. Ed. 1998, 37, 192. (c) Smith, A. B., III;
Doughty, V. A.; Lin, Q.; Zhuang, L.; McBriar, M. D.; Boldi, A. M.; Moser,
W. H.; Murase, N.; Nakayama, K.; Sobukawa, M. Angew. Chem., Int. Ed.
2001, 40, 191. Smith, A. B., III; Lin, Q.; Doughty, V. A.; Zhuang, L.;
McBriar, M. D.; Kerns, J. K.; Brook, C. S.; Murase, N.; Nakayama, K.;
Sobukawa, M. Angew. Chem., Int. Ed. 2001, 40, 196. Smith, A. B., III;
Doughty, V. A.; Sfouggatakis, C.; Bennett, C. S.; Koyanagi, J.; Takeuchi,
M. Org. Lett. 2002, 4, 783. (d) Paterson, I.; Chen. D. Y.-K.; Coster, M. J.;
4820
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