Organic Letters
Letter
In conclusion, we have developed a rapid synthesis of the
stereotetrad core of the briarane diterpenoids. The densely
substituted core structure was accessed in only eight steps from
salicylate ester 5 and features a highly diastereoslective
conjugate addition/β-ketoester alkylation sequence that estab-
lishes the C1 and C10 stereocenters. Work is ongoing to
improve the C14 ketone reduction and C1 allyl addition, which
will enable the total synthesis of brianthein W, briareolate ester
L, and unnatural analogues. These results will be reported in
due course.
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ASSOCIATED CONTENT
Supporting Information
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(13) Briarane numbering used for all synthetic compounds.
*
S
(14) Harned, A. M. Chem. Commun. 2015, 51, 2076−2079.
Experimental procedures, optimized geometries and energies of
all computed species, and NMR spectra for all new compounds.
(15) Wang, H.; Houk, K. N. Chem. Sci. 2014, 5, 462−470.
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AUTHOR INFORMATION
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Trans. 1 1994, 2047−2048.
(19) (a) Dohi, T.; Uchiyama, T.; Yamashita, D.; Washimi, N.; Kita, Y.
Tetrahedron Lett. 2011, 52, 2212−2215. (b) Takenaga, N.; Uchiyama,
T.; Kato, D.; Fujioka, H.; Dohi, T.; Kita, Y. Heterocycles 2011, 82,
Present Address
1
327−1336. (c) Dohi, T.; Takenaga, N.; Fukushima, K.-i.; Uchiyama,
T.; Kato, D.; Shiro, M.; Fujioka, H.; Kita, Y. Chem. Commun. 2010, 46,
691−7699.
20) (a) Zn acetylide: Kno
§
Texas Tech University.
7
(
Notes
̈
lpfel, T. F.; Boyall, D.; Carriera, E. M.
The authors declare no competing financial interest.
Org. Lett. 2004, 6, 2281−2283. (b) Mg acetylide: Ohno, H.; Takeoka,
Y.; Kadoh, Y.; Miyamura, K.; Tanaka, T. J. Org. Chem. 2004, 69,
ACKNOWLEDGMENTS
4
1
(
541−4544. (c) Al acetylide: Ahmar, S.; Fillion, E. Org. Lett. 2014,
6, 5748−5751.
■
Financial support for this project was provided by the National
Science Foundation (1361604). The National Institutes of
Health (S10 OD011952) have supported upgrades to our
NMR facility. Computational resources were provided by the
Minnesota Supercomputing Institute. We thank Prof. Christo-
pher Cramer (U. Minn.) for helpful discussions regarding the
modeling experiments. We thank Dr. Rodolfo Tello-Aburto
21) Unambiguous confirmation of the C1−C10 stereochemical
1
relationship was complicated by overlapping signals in the H NMR
spectrum and no available protons on the alkyne. The assignment was
eventually accomplished using compounds 11a and 11b.
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(New Mexico Tech) and Dr. Kyle Kalstabakken (WuXi
AppTec) for performing exploratory work related to this
project when in our group.
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27) Harned, A. M. Chem. Commun. 2015, 51, 2076−2079.
28) See Supporting Information for details.
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