Scheme 1.
Maoecrystal V: (A) Retrosynthetic Analysis, (B) Model Study, and (C) Synthesis of the Complete Carbon Skeletona
a Reagents and conditions: (a) CAN, NaHCO3, MeOH, 0 °C, 46%; (b) Li(t-BuO)3AlH, THF, -78 °C, 53%; (c) acryloyl chloride, Et3N, DMAP, DCM,
0 °C, 36%; (d) TBSOTf, Et3N, DCM, 63%; (e) Pd/C, O2, PhMe, 110 °C, 99%; (f) Pb(OAc)4, AcOH, 59%; (g) 165 °C, o-DCB, ca. 60%; (h) Ar3BiCl2(13),
DBU, PhMe, 67%; (i) Li(t-BuO)3AlH, THF, -78 °C, 72%; (j) acryloyl chloride, DIEPA, DMAP, DCM, -78 °C, 69%; (k) TFA, DCM, 0 °C, 65%; (l)
Pb(OAc)4, AcOH, 81%, dr ) 3:7; (m) 165 °C, o-DCB, BHT 79% for 20, 69% for 21; (n) BF3·OEt2, DCM, 82%; (o) H2, Pd/C, EtOAc, 97% for 23, 99%
for 24; (p) SmI2, MeOH, THF, 0 °C, 76%, dr ) 17:3. CAN ) cerium ammonium nitrate, DMAP ) 4-dimethylaminopyridine, DCM ) dichloromethane,
TBSOTf ) tert-butydimethylsilyl trifluoromethylsulfonate, o-DCB ) o-dichlorobenzene, DIEPA ) diisopropylethylamine, DBU ) 1,8-diazobicylco[5.4.0]undec-
7-ene, TFA ) trifluoroacetic acid, BHT ) 2,6-di-tert-butyl-p-cresol.
Initial studies (Scheme 1B) with a model system using
ꢀ-keto aldehyde 7 and enol ether 8 led to the generation of
the C-10 quaternary center by treatment with cerium am-
monium nitrate.6 Following reduction of the formyl group
and esterification, silylation of the ketone under a variety of
conditions led only to the undesired regioisomeric dienol
ether 9 (presumably due to the sterically hindered R-proton
at C-9). To circumvent this problem, the diene was further
dehydrogenated (Pd/C, O2) and the resulting aromatic moiety
was oxidized using a Wessely oxidation7 (Pb(OAc)4) to
furnish cyclohexadienone 10 in 59% yield. A Diels-Alder
reaction delivered polycycle 11 in ca. 60% yield (3 mg scale)
upon heating to 165 °C.8 X-ray crystallography confirmed
the structure as that corresponding to the undesired regioi-
someric outcome (based on the position of the geminal
dimethyl group relative to the bicyclic portion of the
molecule). Encouraged by the outcome of the intramolecular
(6) Nair, V.; Mathew, J. J. Chem. Soc., Perkin Trans. 1 1995, 187–
188.
(7) (a) Wessely, F.; Sinwel, F. Monatsh. Chem. 1950, 81, 1055–1070.
(b) Barnes-Seeman, D.; Corey, E. J. Org. Lett. 1999, 1, 1503–1504. (c)
Nicolaou, K. C.; Simonsen, K. B.; Vassilikogiannakis, G.; Baran, P. S.;
Vidali, V. P.; Pitsinos, E. N.; Couladouros, E. A. Angew. Chem., Int. Ed.
1999, 38, 3555–3559. (d) Magdziak, D.; Meek, S. J.; Pettus, T. R. R. Chem.
ReV. 2004, 104, 1383–1429.
(8) For recent examples using o-quinols as dienophiles, see: (a) Nicolaou,
K. C.; Toh, Q.-Y.; Chen, D. Y.-K. J. Am. Chem. Soc. 2008, 130, 11292–
11293. (b) Gao, S.-Y.; Chittimalla, S. K.; Chuang, G. J.; Liao, C.-C. J.
Org. Chem. 2009, 74, 1632–1639. (c) Dory, Y. L.; Roy, A.-L.; Soucy, P.;
Deslongchamps, P. Org. Lett. 2009, 11, 1197–1200. (d) Snyder, S. A.;
Kontes, F. J. Am. Chem. Soc. 2009, 131, 1745–1752.
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