Y. Komatsu et al. / Tetrahedron Letters 54 (2013) 377–380
379
Table 2
Table 3
Control reactions for conditions
Optimization of RCM under irradiation of microwave
Entry
Deoxygenation
Additive
Yielda (%)
Yielda (%)
16
17
13
Entry
P
Additive
1
2
3
4
5
+
—
—
—
—
—
—
—
3
6
5
6
95
85
92
90
79
14
15
16
17
13
À
À
À
À
1
2
Ts
Ts
Ts
CO2Me
—
38
37
45
52
6
17
8
7
11
5
5
9
5
4
3
7
5
21
1,4-BQ
2,6-Dimethyl-1,4-BQ
2,6-Dichloro-1,4-BQ
2,6-Dimethyl-1,4-BQ
1,4-BQ
1,4-BQ
3
16
4b
2
3
a
Isolated yield.
a
Isolated yield.
HG-II (5 mol %) and 1,4-BQ (10 mol %) were used.
b
process,12 possible reaction mechanisms would be HG-II-mediated
oxidation initiated by SET process. This process would be acceler-
ated by the highly strained character of the piperidine ring. Actu-
ally, exposure of substrate 18 possessing less-strained character
of the piperidine ring to ruthenium catalyst did not promote oxida-
tion to the corresponding enamine 19 and starting material 18 was
recovered in almost quantitative yield (Scheme 4). To the best of
our knowledge, there has been no report on oxidation of tertiary
amines with Grubbs’ catalysts.
Finally, we performed extensive investigations to maximize the
yield of the desired RCM reaction. Expecting acceleration effects for
the construction of the highly strained cage-like pentacyclic struc-
ture 14, we examined microwave irradiation13 (Table 3). Fortu-
nately, we observed acceleration of the reaction rate and
improvement of the yield of compound 14 to 38% when a toluene
solution of 13 and HG-II (10 mol %) was heated at 70 °C under
microwave irradiation (entry 1). In addition, it was found that
1,4-BQ slightly improved the yield to 45%. Further optimization
studies on the structure of substrate revealed that a methyl carba-
mate 13 (P = CO2Me) is superior to tosyl amide 13 (P = Ts). Thus,
treatment with HG-II (5 mol %) and BQ (10 mol %) in toluene at
70 °C under the microwave afforded the desired product in 52%
(66% based on the recovered 21% of 13).
scope of RCM for application to a wide range of compounds. Syn-
thetic studies toward strictamine (1) based on the strategy de-
scribed in this Letter are currently under investigation.
Acknowledgments
This work was financially supported by the Cabinet Office,
Government of Japan through its ‘‘Funding Program for Next
Generation World-Leading Researchers (LS008), a Grant-in aid for
Young Scientists (B) (24790003) (for H.U.), and Tohoku University
G-COE program ‘IREMC’. The authors are grateful to Professor
H. Kotsuki of Kochi University for giving Y.K. an opportunity to
conduct research at Kochi University after the 3.11 earthquake.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
In conclusion, we found that Grubbs’ catalysts have a potential
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the construction of highly strained nitrogen-containing polycyclic
structures with the suppression of oxidation and olefin migration.
These observations should be informative for execution of RCM
using alkylamine-containing substrates, and for expansion of the
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Scheme 4. Control reactions for substrate having less-strained piperizine ring.