F
D. Böse, S. E. Denmark
Cluster
Synlett
(6) Denmark, S. E.; Burk, M. T. Proc. Nat. Acad. Sci. 2010, 107, 20655.
(7) Denmark, S. E.; Burk, M. T. Org. Lett. 2012, 14, 256.
(8) Denmark, S. E.; Burk, M. T.; Hoover, A. J. J. Am. Chem. Soc. 2010,
132, 1232.
*
LB* + NBS
Br
OMe
Br+
Ph
Se
Ph
LB*-X+
O
OH
OH
+ Succ–
Ph
(9) (a) Brown, R. S.; Nagorski, R. W.; Bennet, A. J.; McClung, R. E. D.;
Aarts, G. H. M.; Klobukowski, M.; McDonald, R.; Santarsiero, B.
D. J. Am. Chem. Soc. 1994, 116, 2448. (b) Neverov, A. A.; Brown,
R. S. J. Org. Chem. 1996, 61, 962. (c) Brown, R. S. Acc. Chem. Res.
1997, 30, 131.
10c
9f
stabilized
supressed
olefin-to-olefin
isomerization
X
bromiranium ions
(10) Ke, Z.; Tan, C. K.; Chen, F.; Yeung, Y.-Y. J. Am. Chem. Soc. 2014,
136, 5627.
(11) Ke, Z.; Tan, C. K.; Liu, Y.; Lee, K. G. Z.; Yeung, Y.-Y. Tetrahedron
2016, 72, 2683.
(12) Experimental Procedures: Enantioselective Bromocycloether-
ification of 2-{[(tert-butyldimethylsilyl)oxy] methyl}-4-phen-
ylpent-4-en-1-ol (12)
*
OMe
Br+
O
Se
N–
O
Ph
+
OH
A stock solution of 2-{[(tert-butyldimethylsilyl)oxy]methyl}-4-
phenylpent-4-en-1-ol (rac-12) (30 mg/1.0 mL) in CH2Cl2 was
added (1.0 mL, 0.1 mmol) to cyclic sulfide 8 (0.01 mmol, 0.1
equiv) in a septum sealed sample vial at 20 °C. The solution was
cooled to –78 °C, and a second stock solution of chloroacetic
acid in CH2Cl2 (0.1 M, 1.0 mL, 0.1 mmol, 1.0 equiv) was added.
After 10 min at this temperature a stock solution of NBS (0.1 M,
1.0 mL, 0.10 mmol, 1.0 equiv) was slowly added. After 13 h 1 mL
of a stock solution of NaBH4 in EtOH (50 mg/5 mL) was added.
Then the reaction was slowly warmed to 0 °C (over approx. 2 h).
Then 1 mL of H2O and 1 mL of hexanes (HPLC grade) were
added, and the mixture was stirred at 20 °C for 15 min. After
phase separation, the organic phase was filtered through a plug
of MgSO4 and Celite and evaporated using a stream of nitrogen.
The residue was dissolved in CDCl3 and a 1H NMR spectrum was
collected to estimate conversion and product distribution. The
diastereomeric ratio was found to be 13/14 = 41:59. Then the
products were dissolved in THF (2 mL) at 20 °C and TBAF was
added (95 mg, 0.3 mmol, 3.0 equiv). The reaction was stirred at
20 °C until full conversion was observed by TLC analysis (hex-
anes/EtOAc, 90:10). After 2.5 h 10 mL of diethyl ether were
added, and the mixture was washed with sat. aq NH4Cl solution
(1 × 10 mL). The organic layer was dried over MgSO4, filtered,
and evaporated. Purification by column chromatography (hex-
anes/EtOAc, 90:10) yielded the pure products as a diastereo-
meric mixture. HPLC analysis revealed that both diastereoiso-
mers were formed with an enantiomeric ratio of 60:40.
(13) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105, 1735.
(14) For all screening experiments CH2Cl2 with a water content of
>500 μg/mL was applied. A stock solution (0.12 M) of 2,2-
dimethyl-4-phenylpent-4-en-1-ol (17) in CH2Cl2 (0.25 mL, 0.03
mmol) was added to the indicated Lewis base (0.003 mmol,
0.1 equiv) in a septum-sealed sample vial at 20 °C. The solution
was cooled to –78 °C, and a second stock solution of chloroace-
tic acid (CAA) in CH2Cl2 (0.12 M, 0.25 mL, 0.03 mmol, 1.0 equiv)
was added. After 10 min at this temperature a stock solution of
NBS (0.12 M, 0.25 mL, 0.03 mmol, 1.0 equiv) was slowly added.
After 18 h 1 mL of a stock solution of NaBH4 in EtOH (50 mg/5
mL) was added. Then the reaction was slowly warmed to 0 °C
(over approx. 2 h). Then 1 ml of H2O and 1 mL of hexanes (HPLC
grade) were added, and the mixture was stirred at 20 °C for 15
min. After phase separation, the organic phase was filtered
through a plug of MgSO4 and Celite and evaporated using a
stream of nitrogen. The residue was dissolved in CDCl3 and a 1H
Scheme 7 Mechanistic rationale for a suppressed olefin-to-olefin isom-
erization through a stabilization of the intermediate bromiranium ion
by a Lewis base catalyst with an additional coordination side in the cata-
lyst´s structure
Funding Information
We are grateful to the National Institutes of Health (R01 GM085235)
for financial support.
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Supporting Information
Supporting information for this article is available online at
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References and Notes
(1) New current address: Dietrich Böse, Boehringer Ingelheim RCV
GmbH & Co KG, Dr.-Boehringer-Gasse 5-11, 1121 Vienna,
Austria; e-mail: dietrich.boese@boehringer-ingelheim.com.
(2) (a) Dowle, M. D.; Davies, D. I. Chem. Soc. Rev. 1979, 8, 171.
(b) Chen, G.; Ma, S. Angew. Chem. Int. Ed. 2010, 49, 8306.
(c) Murai, K.; Matsushita, T.; Nakamura, A.; Fukushima, S.;
Shimura, M.; Fujioka, H. Angew. Chem. Int. Ed. 2010, 49, 9174.
(d) Nakatsuji, H.; Sawamura, Y.; Sakakura, A.; Ishihara, K.
Angew. Chem. Int. Ed. 2014, 53, 6974. (e) Hennecke, U.; Müller,
C. H.; Fröhlich, R. Org. Lett. 2011, 13, 860.
(3) (a) French, A. N.; Bissmire, S.; Wirth, T. Chem. Soc. Rev. 2004, 33,
354. (b) Snyder, S. A.; Treitler, D. S.; Brucks, A. P. Aldrichimica
Acta 2011, 44, 27. (c) Hennecke, U. Chem. Asian J. 2012, 7, 456.
(d) Tan, C. K.; Zhou, L.; Yeung, Y.-Y. Synlett 2011, 1335.
(e) Gieuw, M. H.; Ke, Z.; Yeung, Y.-Y. Chem. Rec. 2017, 17, 287.
(4) (a) Denmark, S. E.; Kuester, W. E.; Burk, M. T. Angew. Chem. Int.
Ed. 2012, 51, 10938. (b) Beutner, G. L.; Denmark, S. E. In Invent-
ing Reactions;4V4o.
l
Goossen, L. J., Ed.; 2013, 55.
(5) (a) Denmark, S. E.; Chi, H. M. J. Am. Chem. Soc. 2014, 136, 3655.
(b) Denmark, S. E.; Eklov, B. M.; Yao, P. J.; Eastgate, M. D. J. Am.
Chem. Soc. 2009, 131, 11770. (c) Denmark, S. E.; Jaunet, A. J. Am.
Chem. Soc. 2013, 135, 6419. (d) Denmark, S. E.; Jaunet, A. J. Org.
Chem. 2014, 79, 140.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–G
B?se, Dietrich
