Development of palladium(II)-catalyzed oxidative cyclization of olefinic keto and/or lactone esters

Article abstract of DOI:10.1016/j.tetlet.2009.06.052

A highly efficient palladium-catalyzed oxidative cyclization of olefinic keto and/or lactone esters, which features a catalytic cyclization employing one atmosphere of oxygen as a reoxidizing agent, is developed.

Full text of DOI:10.1016/j.tetlet.2009.06.052

Tetrahedron Letters 50 (2009) 4888–4891
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Tetrahedron Letters
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Development of palladium(II)-catalyzed oxidative cyclization of olefinic
keto and/or lactone esters
Ayaka Hibi, Masahiro Toyota *
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient palladium-catalyzed oxidative cyclization of olefinic keto and/or lactone esters, which
features a catalytic cyclization employing one atmosphere of oxygen as a reoxidizing agent, is developed.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 12 May 2009
Revised 8 June 2009
Accepted 11 June 2009
Available online 13 June 2009
Recently, we developed a palladium-catalyzed cycloalkenyla-
tion, which has been successfully adapted to the stereoselective
syntheses of polycyclic natural products (Scheme 1).1
,2
In our efforts to expand the utility of this palladium-catalyzed
cycloalkenylation, we undertook a concise synthesis of 6-oxatricy-
1
,5
clo[6.3.0.0 ]undecane, which is the BCD ring system of ginkgolide
C (Fig. 1).
Scheme 1.
Although ketene silyl acetal 13 gave rise to desired tricyclic
compound 2 under palladium-catalyzed cycloalkenylation condi-
4
tions, the yield was less than 11% probably due to the instability of
ketene silyl acetal 1 (Scheme 2).3
To solve this problem, we recently developed a novel method to
construct the aforementioned 6-oxatricyclo[6.3.0.01 ]undecane.
Thus, desired compound 4 can be synthesized in good yield by pal-
ladium-promoted oxidative cyclization of olefinic lactone ester 3
,5
4
5
(
Scheme 3). A related intermolecular reaction is reported, how-
ever, this reaction can give the desired cyclization products under
neutral reaction conditions.
Figure 1.
However, to expand the utility of the cyclization, herein we re-
port the preliminary results of our efforts to develop a catalytic
version of this reaction in which olefinic keto and/or lactone esters
are effectively converted into the corresponding cyclization
products.
Requisite substrates were prepared as depicted in Scheme 4.
6
Namely, lactone 5 was treated with methyl chloroformate in the
presence of lithium hexamethyldisilazide to afford lactone ester
Scheme 2.
7
6
in 93% yield.
Table 1 summarizes the various reaction conditions on the con-
version of olefinic lactone ester 6 to exo-olefin 7.7 Initially, 6 was
treated with a stoichiometric amount of Pd(OAc)
solvent, which gave desired product 7 in 28% isolated yield (entry
). To convert this reaction into a catalytic process, numerous reac-
2
in DMSO as a
1
*
Corresponding author. Tel./fax: +81 72 254 9164.
E-mail address: toyota@c.s.osakafu-u.ac.jp (M. Toyota).
Scheme 3.
0
040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.052

A. Hibi, M. Toyota / Tetrahedron Letters 50 (2009) 4888–4891
4889
tion parameters, including the palladium catalyst, the amount of
catalyst, temperature, and solvent, were evaluated (entries 2–14).
Because DMSO was a suitable solvent for the palladium-catalyzed
1
a
cycloalkenylation, the cyclization reaction was attempted using 6
in the presence of a catalytic amount of the palladium catalyst un-
der one atmosphere of oxygen in DMSO (entries 2–11). Although
employing Pd(acac)
2
, PdCl
2
(MeCN)
2
, or PdCl
2
did not yield the
Scheme 4.
Table 1
Palladium-catalyzed cyclization of lactone ester 6
Entry
Solvent
Catalyst
Pd(OAc)
Pd2+ (mol %)
Temperature (°C)
Yieldb (%)
1a
2
3
4
5
6
7
8
9
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
100
10
10
10
10
10
10
10
5
5
5
10
10
10
rt
28
—
—
—
2
Pd(acac)
2
45
45
45
45
rt
45
60
rt
45
60
45
45
45
PdCl
PdCl
2
(MeCN)
2
2
Pd(OCOCF
3
)
3
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
Pd(OAc)
2
2
2
2
2
2
2
2
2
42 (56)
78 (81)
74
54 (84)
57 (79)
47 (70)
33 (47)
15 (26)
23 (37)
10
11
12
13
14
THF
MeCN
a
Reaction was carried out under one atmosphere of argon.
Values in parentheses refer to yield based upon recovered starting materials. rt = room temperature.
b
Table 2
Conversion of keto and/or lactone esters to five-membered ring
Entry
Substrate
Temperature (°C)
Productb
Yielda (%)
10
11
12
Cyclized products
1
2
3
rt
43 (75)
58
2
0
0
5
45
81
80
45
60
23
34
41
4
5
45
60
76
84
6
7
45
60
69 (82)
31 (50)
16
17
Cyclized products
8
9
45
60
38 (76)
17 (37)
31
20
69
37
a
Values in parentheses refer to yield based upon recovered starting materials.
Relative stereochemistry was established using NOE experiments employing cyclized products (Fig. 2).
b

4
890
A. Hibi, M. Toyota / Tetrahedron Letters 50 (2009) 4888–4891
1
1
Analyses of the H– H COSY experiments of 7, 10, 14, and 16 en-
abled all the protons of each compound to be assigned. Addition-
ally, the relative stereochemistries were established on the basis
of NOE correlations, as shown in Figure 2.
The carbomethoxy group at the angular position of tricyclic
cyclization product 4 could be easily removed under the Krapcho
4
reaction conditions without isomerization of the olefin. Although
Scheme 5.
Liu and co-workers have reported an efficient palladium-catalyzed
1
4
methylene-cyclopentane annulation process, the present proto-
col should be more effective due to its adaptability not only for var-
ious types of olefinic keto esters, but also for lactone esters.
cyclized product, 3% of 7 was isolated in the presence of 10 mol %
of Pd(OCOCF (entry 5). On the other hand, when the reaction
was conducted using Pd(OAc) as the catalyst, the cyclization yield
3 2
)
2
Acknowledgments
rose to 42% (entry 6). Moreover, heating the reaction mixture
accelerated the cyclization, providing 7 in 78% yield (entry 7). Fur-
ther increasing the temperature had a negligible effect on the yield
entry 8). When the reaction was carried out employing 5 mol % of
Pd(OAc) , the yield of the cyclized product decreased (entries 9–
1). Other solvents, such as DMF, THF, and MeCN, were unsuitable
for this catalytic cyclization (entries 12–14). It was found that this
catalytic cyclization proceeds smoothly under palladium-catalyzed
cycloalkenylation conditions.
With the optimal reaction conditions in hand, we examined the
effectiveness of this new methodology on the conversion of a vari-
ety of b-keto and/or lactone esters to the corresponding cyclized
products. Table 2 summarizes the results.
Part of this research was supported by a Grant-in-Aid for Scien-
tific Research on Priority Areas 18390007 from the Ministry of Edu-
cation, Culture, Sports, Science, and Technology (MEXT).
(
2
1
References and notes
1
.
.
(a) Toyota, M.; Wada, T.; Ihara, M. J. Am. Chem. Soc. 1998, 120, 4916–4925; (b)
Toyota, M.; Wada, T.; Ihara, M. J. Org. Chem. 2000, 65, 4565–4570; (c) Toyota,
M.; Odashima, T.; Wada, T.; Ihara, M. J. Am. Chem. Soc. 2000, 122, 9036–9037;
(
d) Toyota, M.; Sasaki, M.; Ihara, M. Org. Lett. 2003, 5, 1193–1195; (e) Toyota,
M.; Asano, T.; Ihara, M. Org. Lett. 2005, 7, 3929–3932.
2
(a) Toyota, M.; Rudyanto, M.; Ihara, M. Tetrahedron Lett. 2000, 41, 8929–8932;
(b) Toyota, M.; Rudyanto, M.; Ihara, M. J. Org. Chem. 2002, 67, 3374–3386; (c)
Toyota, M.; Ilangovan, A.; Okamoto, R.; Masaki, T.; Arakawa, M.; Ihara, M. Org.
Lett. 2002, 4, 4293–4296; (d) Toyota, M.; Ihara, M. Synlett 2002, 1211–1222; (e)
Toyota, M. J. Syn. Org. Chem. Jpn. 2006, 64, 25–33.
Because the bicyclo[3.3.0]octane ring unit is found in important
biologically active compounds,8,2c the catalytic reaction was ini-
7
tially adapted to synthesize that ring system. Compound 9 was
3. Takeda, K. Thesis, Osaka Prefecture University, 2007.
4. Hibi, A.; Takeda, K.; Toyota, M. Heterocycles 2009, 77, 173–177.
prepared from 2-carbomethoxycyclo-pent-2-enone 89 via a 1,4-
conjugate addition of the homoallyl group (Scheme 5).10
5.
Hegedus, L. S.; Williams, R. E.; McGuire, M. A.; Hayashi, T. J. Am. Chem. Soc.
980, 102, 4973–4979.
1
When the reaction was performed at room temperature with b-
keto ester 9, exo-olefin 10 was isolated in 43% yield along with 2%
of endo-isomer 11 (entry 1). Increasing the reaction temperature
to 45 °C increased the yield of 10, but 11 was formed in 23% yield
6.
Ohmiya, H.; Tsuji, T.; Yorimitsu, H.; Oshima, K. Chem. Eur. J. 2004, 10, 5640–
11
5648.
7. Data for new compounds: Compound 6: IR(KBr) 1782, 1739 cm ; 1H NMR
À1
1
2
(
400 MHz, CDCl
3
) d 1.56–1.74 (m, 2H), 2.05–2.11 (m, 1H), 3.00 (ddt, J = 16.4,
8.0, 8.0 Hz, 2H), 3.26 (d, J = 9.2 Hz, 1H), 3.81 (s, 3H), 3.92 (dd, J = 8.6, 8.6 Hz, 1H),
(
entry 2). Further increasing the reaction temperature did not af-
4.52 (dd, J = 8.8, 8.0 Hz, 1H), 5.01–5.06 (m, 2H), 5.75 (ddt, J = 17.2, 10.4, 6.7 Hz,
1H); 13C NMR (100 MHz, CDCl ) d 31.2, 31.7, 39.7, 52.5, 53.2, 72.1, 116.2, 136.8,
7
3
fect the yield of 10, but isomer 12 was generated in 5% yield (entry
). When this catalytic cyclization was then subjected to bicyclic
+
+
1
68.2, 172.0; LRMS m/z 198 (M ), 143; HRMS calcd for C10H O
found 198.0887. Compound 7: IR(KBr) 1778, 1744 cm
14
4
(M ) 198.0892,
; H NMR (400 MHz,
3
À1
1
lactone ester 3 at 45 °C, desired cyclized product 4 was synthesized
in 76% yield (entry 4). Heating of reaction mixture at 60 °C was the
3
CDCl ) d 1.63 (dddd, J = 12.8, 7.8, 7.7, 7.6 Hz, 1H), 2.15 (ddd, J = 13.0, 7.4, 7.0 Hz,
1
4
2
H), 2.52–2.57 (m, 2H), 3.42 (dddd, J = 7.2, 7.2, 7.2, 4.0 Hz, 1H), 3.79 (s, 3H),
.03 (dd, J = 9.2, 4.0 Hz, 1H), 4.46 (dd, J = 9.4, 7.4 Hz, 1H), 5.32 (dd, J = 2.0,
best condition, as 4 was obtained in 84% yield (entry 5). Substrate
13
.0 Hz, 1H), 5.57 (dd, J = 2.2, 2.2 Hz, 1H); C NMR (100 MHz, CDCl ) d 29.8,
3
7
+
1
3 , which was prepared in the same manner described in Scheme
33.5, 47.2, 53.5, 63.2, 70.5, 113.3, 145.8, 168.9, 173.0; LRMS m/z 196 (M ),
7
+
1
52,120, 93, 77; HRMS calcd for C10
Compound 9: IR(KBr) 1758, 1730, 1641 cm
.41–1.56 (m, 2H), 1.63–1.72 (m, 1H), 2.01–2.45 (m, 5H), 2.53–2.64 (m, 1H),
2.84 (d, J = 10.8 Hz, 1H), 3.74 (s, 3H), 4.97 (ddd, J = 10.6, 1.2, 1.0 Hz, 1H), 5.02
(dd, J = 17.2, 1.6 Hz, 1H), 5.79 (ddt, J = 17.2, 10.4, 6.7 Hz, 1H); 13
NMR
100 MHz, CDCl ) d 27.3, 31.4, 34.2, 38.6, 41.0, 52.6, 61.9, 115.2, 137.9, 170.0,
H O (M ) 196.0736, found 196.0732.
12 4
4
, was also suitable for this cyclization process, and led to 14 as
À1
1
;
3
H NMR (400 MHz, CDCl ) d
the sole product in 69% yield (entry 6). Cyclization at 60 °C de-
creased the yield of cyclized product 14 to 31% (entry 7). Only
exo-isomer 14 was generated, when the reaction was conducted
using 13 as the substrate. On the other hand, treating keto ester
1
C
(
2
1
3
+
+
11.8; LRMS m/z 196 (M ), 109; HRMS calcd for C11H O
96.1095. Compound 12: IR(KBr) 1749, 1732 cm
16
3
(M ) 196.1099, found
H NMR (400 MHz, CDCl
1
3
1
5
with Pd(OAc)
2
at 45 °C provided two cyclization products,
À1 1
;
3
)
7
7
exo-olefin 16 (38%) and endo-isomer 17 (31%). However, increas-
ing the reaction temperature to 60 °C decreased the yield of cycli-
zation products 16 and 17. Through these experiments, substrates
d 1.08 (d, J = 7.2 Hz, 3H), 1.87–1.95 (m, 1H), 2.09–2.23 (m, 2H), 2.31–2.40 (m,
1
2
1
H), 3.53–3.61 (m, 1H), 3.71 (s, 3H), 3.76–3.79 (m, 1H), 5.48 (ddd, J = 5.6, 2.4,
.4 Hz, 1H), 5.58 (ddd, J = 5.6, 2.0, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl
) d
6.3, 25.1, 38.5, 46.7, 52.7, 54.6, 67.1, 130.0, 136.2, 172.0, 213.8; LRMS m/z 194
3
+
+
1
3 and 15 turned out to be temperature sensitive.
(M ), 84; HRMS calcd for C11
H
14
O
3
(M ) 194.0943, found 194.0939. Compound
H NMR (400 MHz, CDCl ) d 1.36–1.45 (m, 1H), 1.50–
.64 (m, 2H), 2.01–2.20 (m, 3H), 2.41 (dddd, J = 14.2, 9.4, 9.4, 5.0 Hz, 1H), 3.26
À1
1
1
1
3: IR(KBr) 1747 cm
;
3
(
d, J = 9.6 Hz, 1H), 3.75 (s, 0.2H), 3.80 (s, 2.8H), 4.33 (ddd, J = 11.5, 10.0, 3.6 Hz,
1
1
6
H), 4.41 (ddd, J = 11.6, 4.8, 4.8 Hz, 1H), 4.98–5.06 (m, 2H), 5.75 (ddt, J = 17.2,
0.4, 6.6 Hz, 1H); 13C NMR (100 MHz, CDCl
) d 27.3, 30.5, 34.1, 34.5, 53.0, 54.3,
8.4, 115.7, 137.3, 167.5, 169.5; LRMS m/z 212 (M ), 157; HRMS calcd for
3
+
+
À1
C
11
H
16
O
4
(M ) 212.1049, found 212.1036. Compound 14: IR(KBr) 1730 cm
;
1
H NMR (400 MHz, CDCl
3
) d 1.53 (dddd, J = 12.8, 7.8, 7.8, 6.4 Hz, 1H), 1.68
(
(
dddd, J = 14.3, 10.2, 8.6, 4.0 Hz, 1H), 1.94–2.08 (m, 2H), 2.50–2.56 (m, 2H), 3.01
ddd, J = 13.3, 8.7, 6.8 Hz, 1H), 3.77 (s, 3H), 4.24 (ddd, J = 11.4, 10.2, 3.0 Hz, 1H),
4
2
1
.36 (ddd, J = 11.5, 4.8, 4.4 Hz, 1H), 5.32 (dd, J = 2.0, 2.0 Hz, 1H), 5.40 (dd, J = 2.0,
.0 Hz, 1H); 13C NMR (100 MHz, CDCl
) d 27.2, 30.3, 31.4, 42.9, 53.4, 63.7, 67.7,
13.6, 146.7, 168.3, 170.9; LRMS m/z 210 (M ), 107; HRMS calcd for C11
3
+
H O
14 4
À1
M ) 210.0892, found 210.0874. Compound 16: IR(KBr) 1739, 1717 cm ; 1
+
H
(
NMR (400 MHz, CDCl
3
) d 1.49–1.59 (m, 2H), 1.64–1.73 (m, 1H), 1.81–1.98 (m,
3
3
H), 2.33–2.45 (m, 2H), 2.47–3.01 (m, 2H), 3.03 (ddd, J = 12.0, 8.4, 6.4 Hz, 1H),
.75 (s, 3H), 4.96 (dd, J = 2.4, 2.4 Hz, 1H), 5.23 (dd, J = 2.2, 2.2 Hz, 1H); 13C NMR
(
100 MHz, CDCl
3
) d 24.0, 26.2, 28.4, 30.0, 39.5, 47.9, 52.9, 72.1, 112.2, 148.1,
+ +
Figure 2.
171.4, 206.2; LRMS m/z 208 (M ), 176; HRMS calcd for C12H O (M ) 208.1099,
16 3

A. Hibi, M. Toyota / Tetrahedron Letters 50 (2009) 4888–4891
4891
found 208.1089. Compound 17: IR(KBr) 1739, 1712 cm ; 1H NMR (400 MHz,
À1
9. Bernardi, A.; Karamfilova, K.; Sanguinetti, S.; Scolastico, C. Tetrahedron 1997, 53,
13009–13026.
3
CDCl ) d 1.55–1.62 (m, 1H), 1.78 (dd, J = 3.6, 2.0 Hz, 3H), 2.06 (dddd, J = 16.4,
8
1
.8, 4.8, 2.4 Hz, 1H), 2.24–2.31 (m, 2H), 2.41 (dddd, J = 16.8, 10.0, 4.4, 2.4 Hz,
H), 2.45–2.53 (m, 1H), 3.13 (ddd, J = 11.6, 7.2, 6.0 Hz, 1H), 3.74 (s, 3H), 3.13
10. (a) Horiguchi, Y.; Matsuzawa, S.; Nakamura, E.; Kuwajima, I. Tetrahedron Lett.
1986, 27, 4025–4028; (b) Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.;
Kuwajima I. Tetrahedron Lett. 1986, 27, 4029–4032.
1
3
(
ddd, J = 11.6, 7.2, 6.0 Hz, 1H), 3.74 (s, 3H); C NMR (100 MHz, CDCl
3
) d 15.5,
2
2.5, 27.8, 36.4, 40.3, 46.9, 52.6, 73.1, 129.6, 139.0, 172.7, 209.1; LRMS m/z 208
11. Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526–
4527.
+
+
(
16 3
M ); HRMS calcd for C12H O (M ) 208.1099, found 208.1089.
8
.
(a) Singh, V.; Thomas, B. Tetrahedron 1998, 54, 3647–3692; (b) Delgado, A.;
Rodrıríguez, J. R.; Castedo, L.; Mascareñas, J. L. J. Am. Chem. Soc. 2003, 125,
12. Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew. Chem., Int. Ed. 2004, 43,
5350–5352.
9
282–9283; (c) Kendhale, A. M.; Gonnade, R.; Rajamohanan, P. R.; Sanjayan, G.
13. Bunce, R. A.; Harris, C. R. Synth. Commun. 1996, 26, 1969–1975.
14. Kung, L.; Tu, C.; Shia, K.; Liu, H. Chem. Commun. 2003, 2490–2491.
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