H.-Y. Lee et al.
COMMUNICATION
17: 1H NMR (400 Hz, CDCl3): d=3.72 (s, 3H), 2.92 (m, 1H), 2.80 (m,
1H), 2.49 (m, 2H), 2.20 (m, 1H), 2.10 (t, 3H), 1.75 (m, 2H), 1.44 (d, J=
14.45 Hz, 1H), 1.38 (m, 1H), 1.27 (m, 1H), 1.19 (s, 3H), 1.10 (s, 3H),
0.75 ppm (d, J=7.51 Hz, 3H); 13C NMR (100 Hz, C6D6): d=166.46,
155.82, 127.49, 93.68, 62.87, 61.80, 52.70, 50.66, 47.84, 35.67, 31.88, 30.86,
30.12, 27.12, 20.97, 13.18, 11.07 ppm; IR (neat): n˜ =3477, 3061, 2982,
2933, 1731, 1490, 1446, 1368, 1247, 1189, 1096, 1032, 932 cmÀ1; High reso-
lution MS (ESI): Calculated for C17H26O3 [M+Na]+: 301.1780, found:
301.1814.
18: 1H NMR (400 Hz, CDCl3): d=3.71 (s, 3H), 2.90–2.83 (m, 1H), 2.32
(m, 1H), 2.20 (m, 2H), 2.10 (t, 3H), 1.78 (m, 2H), 1.60 (m, 1H), 1.35 (d,
J=13.60 Hz, 1H), 1.18 (s, 3H), 1.15 (m, 1H), 1.13 (s, 3H), 1.05 (m, 1H),
1.04 ppm (d, J=6.44 Hz, 3H); 13C NMR (100 Hz, C6D6): d=166.63,
156.19, 126.97, 93.95, 68.25, 66.04, 55.62, 50.71, 48.24, 45.48, 37.19, 36.52,
31.80, 27.31, 24.46, 18.67, 13.10 ppm; IR (neat): n˜ =3500, 2949, 2865,
1699, 1645, 1436, 1373, 1347, 1323, 1266, 1220, 1177, 1126, 1109, 1082,
1064, 1036, 1008, 950 cmÀ1; High resolution MS (ESI): Calculated for
C17H26O3 [M+Na]+: 301.1780, found: 301.1814.
stepwise fashion and the first cyclization step could form
either intermediate I or II. Intermediate I is produced
through 6-endo-trig-cyclization that sets the relative stereo-
chemistry between the bridgehead methyl group and the bi-
cyclic structure of 14. The second cyclization proceeds via
the less-sterically demanding 5-exo-trig-cyclization to pro-
duce 14 stereoselectively. Intermediate II is produced
through a 5-exo-trig-cyclization that sets the trans-stereo-
chemistry at the ring junction of the final product. The ini-
tially formed intermediate II would adopt the sterically less-
congested conformer IIꢀ during the second ring formation.
At this stage, the stereochemical integrity of the methyl
group attached to the olefin in the substrate was lost. The
methyl group adopts the sterically less-congested conforma-
tion for the final cyclization reaction to form 13. This result,
along with the previous reports by Little and co-workers,[19]
suggests that the cycloaddition reaction pathways to either
linearly fused triquinanes or tricyclo[5.3.1.02,6]undecanes
could be controlled by judicious choice of the substitution
patterns of the tether and the diylophile.
Acknowledgements
In summary, the high reactivity of the TMM-diyl-mediat-
ed [2+3] cycloaddition reaction was demonstrated by the
production of trans-syn-tricyclo[6.3.0.02,6]undecane without
the formation of its cis isomer. The formation of the bridged
bicyclic, tricyclo[5.3.1.02,6]undecane structure from 1,2-disub-
stituted diylophile provides another useful information to
control the regioselectivity during the [2+3] cycloaddition
reaction of the TMM diyl. As the conversion of the Mel-
drumꢀs acid unit into the corresponding ketone was success-
ful, this synthetic strategy could be applied to the total syn-
thesis of various natural products with related structural fea-
tures.[20]
This research was supported by the Basic Science Research Program
through the National Research Foundation of Korea (NRF) funded by
the Ministry of Education, Science and Technology (KRF-2008-314-
C00198).
Keywords: cycloaddition · diradicals · fused-ring systems ·
natural products · triquinanes
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Experimental Section
Potassium bis(trimethylsilyl)amide (KHMDS; 2.64 mL of a 0.5m solution
in toluene, 1.32 mmol) was added to a stirred solution of 4 (300 mg,
1.0 mmol) in THF (90 mL) at 08C. After being stirred for 30 min at 08C,
the mixture was warmed to room temperature for 20 min. The solution
of propynyl iodonium salt (560 mg, 1.42 mmol) in THF (60 mL) was
added for 30 min via cannula. The resulting reaction mixture was stirred
for 2 h. The solvent was evaporated in vacuo and purified by flash
column chromatography on silica gel (EtOAc/Hexane=1:10) to give
300 mg (0.90 mmol, 88%) of a mixture of 13 and 14. 3-Chloroperoxyben-
zoic acid (mCPBA; 0.334 g of 77% contents, 1.35 mmol) was added to a
stirred solution of the mixture of 13 and 14 (300 mg, 0.90 mmol) in meth-
ylene chloride (10 mL) at room temperature. The mixture was stirred for
24 h and diluted with Et2O. Na2S2O3·5H2O in H2O was added to the mix-
ture and stirred for 30 min. The aqueous layer was extracted with Et2O
(2ꢂ10 mL). The combined organic layers were dried over MgSO4, con-
centrated, and purified by flash column chromatography on silica gel
(EtOAc/Hexane=1:10) to give 241 mg (0.69 mmol, 77%) of epxodies.
Copper powder (5 mg, 0.08 mmol) was added to the stirred solution of
epoxides (223 mg, 0.64 mmol) in pyridine/MeOH (5.5 mL, v/v=10:1) and
the mixture was refluxed for 3 h. The reaction mixture was cooled to
room temperature. 1 m HCl was added and the aqueous layer was ex-
tracted with Et2O (2ꢂ10 mL). The combined organic layers were dried
over MgSO4, and concentrated at reduced pressure. The residue was pu-
rified by flash column chromatography on silica gel (EtOAc/Hexane=
1:20 to 1:10) to give 17 (51 mg, 28.5%) as a white solid and 18 (94 mg,
52.5%) as a colorless oil.
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Nguyen, S. L. Midland, J. J. Sim, F. S. Than, J. Essent. Oil Res. 2004,
16, 571–578. Presilpiperfolanol: d) R. M. Coates, Z. Ho, M. Klobus,
mann, C. Zdero, J. Jakupovic, H. Robinson, R. M. King, Phytochem-
8053–8060; f) L. Van Hijfte, R. D. Little, J. L. Petersen, K. D. Moel-
Strachan, N. R. Trenner, B. H. Arison, R. Hirschman, J. M. Chemer-
[7] a) B. Trillo, M. Gulias, F. Lopez, L. Castedo, J. L. Mascarenas, Adv.
[8] S. Yamago, E. Nakamura, Org. React. 2002, 61, 1–217.
1934
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Chem. Asian J. 2011, 6, 1931 – 1935