Next, we investigated the stereoselective synthesis of the
anti-diepoxide 6 (Scheme 5). The transformation from the
key synthetic intermediate 11 to 6 is similar to that toward
5. The allylic alcohol 11 was subjected to Sharpless asym-
metric epoxidation2 using (ꢀ)-DIPT, giving anti-diepoxide
19 as a single stereoisomer in 81% yield.15 Parikhꢀ
Doering oxidation8 of 19 followed by dibromoole-
fination11 and desilylation/dehydrobromination12b pro-
vided bromoacetylene 20 in 57% yield in three steps. The
bromoacetylene 20 (1.0 equiv) was coupled with the dia-
cetylene 17 (1.1 equiv) by CadiotꢀChodkiewicz reaction3
under the optimized conditions affording triacetylene 21.14
The final transformation, acetylation and desilylation, was
performed to provide the anti-diepoxide 6.
Figure 3. Chemical shift differences (ΔδSꢀR) of (S)- and (R)-14.
R = MTPA. MTPA = R-methoxy-
R-(trifluoromethyl)phenylacetyl.
and subsequent one-carbon homologation with CBr4/
PPh3/Et3N11,12 gave dibromoolefin 15. Treatment of 15
with TBAF (4.0 equiv) induced desilylation and dehydro-
bromination simultaneously to afford bromoacetylenic
alcohol 16.12b After the detailed investigation on the
introduction of the triacetylenic moiety, it was found that
CadiotꢀChodkiewicz reaction3 between 16 (1.0 equiv) and
diacetylene 17 (1.1 equiv)13 with CuCl/NH2OH•HCl/
EtNH2 at ꢀ78 °C proceeded smoothly to provide triace-
tylene 18.14 Finally, acetylation of the alcohol 18 and
The synthetic diepoxides 5 and 6 were submitted to
extensive NMR analysis. The selected Δδ values in ppm
between natural (ꢀ)-gummiferol and the synthetic pro-
ducts inthe1Hand13C NMR spectra are depicted in Table 1.
The 1H and 13C NMR data of the synthetic syn-diepoxide 5
were in good agreement with those of natural (ꢀ)-
gummiferol.1,16 On the other hand, the 1H and 13C NMR
data of the synthetic anti-diepoxide 6 were different from
those of the natural product.1,16 It was observed that the
chemical shift differences between the natural product and
synthetic 6 at the C9 and C10 positions were significant:
þ0.08 (H-9), þ0.12 (H-10), ꢀ1.23 (C-9), and ꢀ0.88 (C-10).
subsequent deprotection of the TBS group with HF pyr
afforded the syn-diepoxide 5.
3
The measured specific rotation of the synthetic 5, [R]28
D
Scheme 4. Synthesis of 5
ꢀ62.5 (c 0.07, CH3OH), was consistent with that of the
natural product.17,18 Therefore, we concluded that the
absolute configuration of (ꢀ)-gummiferol was that de-
scribed in 5.
Scheme 5. Synthesis of 6
(11) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 3769.
(12) In the absence of Et3N, only a trace amount of 15 was obtained
because the epoxide opening occurred as a side reaction. For the related
examples, see: (a) Grandjean, D.; Pale, P.; Chuche, J. Tetrahedron Lett.
ꢀ
1994, 35, 3529. (b) Gonzalez, I. C.; Forsyth, C. J. J. Am. Chem. Soc.
2000, 122, 9099. (c) Dıaz, D.; Martın, T.; Martın, V. S. J. Org. Chem.
2001, 66, 7231.
(14) The homocoupling byproduct was not observed at all.
(15) The diastereomeric purity of 19 was determined by the 1H and
13C NMR spectra, which were clearly different from those of 12.
(16) See Supporting Information for details.
€
(13) Reber, S.; Knopfel, T. F.; Carreira, E. M. Tetrahedron 2003, 59,
6813.
3646
Org. Lett., Vol. 13, No. 14, 2011