Palladium-catalyzed intra-molecular olefin insertion reaction of α-alkenyl-α-acyloxytrialkylsilane. Synthesis of optically active carbocycle

Article abstract of DOI:10.1016/j.tetlet.2007.03.029

Pd-catalyzed intra-molecular olefin insertion/carbonylation reaction of optically active α-alkenyl-α-acyloxysilanes is described. The reactions proceeded in a stereoselective manner to give five- and six-membered optically active carbocycles having (E)-vinylsilane in their side chains. Under CO condition, optically active carbocycles containing one-carbon homologated side chain were produced by Pd-catalyzed tandem olefin insertion-carbonylation reaction.

Full text of DOI:10.1016/j.tetlet.2007.03.029

Tetrahedron Letters 48 (2007) 3925–3928
Palladium-catalyzed intra-molecular olefin insertion
reaction of a-alkenyl-a-acyloxytrialkylsilane. Synthesis
of optically active carbocycle
*
*
Kazuhiko Sakaguchi, Takuya Okada, Takeshi Yamada and Yasufumi Ohfune
Graduate School of Science, Department of Material Science, Osaka City University, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
Received 7 February 2007; revised 2 March 2007; accepted 6 March 2007
Available online 12 March 2007
Abstract—Pd-catalyzed intra-molecular olefin insertion/carbonylation reaction of optically active a-alkenyl-a-acyloxysilanes is
described. The reactions proceeded in a stereoselective manner to give five- and six-membered optically active carbocycles having
(
E)-vinylsilane in their side chains. Under CO condition, optically active carbocycles containing one-carbon homologated side chain
were produced by Pd-catalyzed tandem olefin insertion–carbonylation reaction.
Ó 2007 Elsevier Ltd. All rights reserved.
Optically active a-alkenyl-a-acyloxysilane has received
significant attention because of its chirality transferring
property from the a- to c-position through a cationic
could be generated from optically active a-alkenyl-a-
acyloxysilane using a Pd catalyst. This reactive species
3
was trapped by an external or internal nucleophile to
give an acyclic or cyclic c-substituted vinylsilane, exclu-
sively, where the a-silyl group played a crucial role for
the regio- and stereo-selective C–C bond forming reac-
1
rearrangement or an electrocyclic rearrangement of its
2
acyloxy-derived enolate. In the previous report, we
demonstrated that a novel p-allyl palladium species, an
equivalent of a putative a,c-silylallyl cation (Fig. 1),
4
tions owing to its steric and stereo-electronic features.
Nu
OAc
TBDMS
*
Nu
base
TBDMS
TBDMS
L
L
*
EWG
OAc
Pd(0)
EWG
EWG
EWG
Pd
TBDMS
TBDMS
TBDMS
*
*
complete chirality transfer
α
γ
chiral
α,γ -silylallyl cation
Pd(0)
AcO
TBDMS
*
Pd
OAc
CO
*
TBDMS
TBDMS
RO C
2
*
A
TBDMS
*
Figure 1.
Keywords: Pd-catalyzed cyclization; Olefin insertion; a-Acyloxysilane; p-Allyl palladium; Chirality transfer; Vinylsilane.
*
Corresponding authors. Tel.: +81 6 6605 2571; fax: +81 6 6605 2522 (K.S.); e-mail: sakaguch@sci.osaka-cu.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.03.029

3926
K. Sakaguchi et al. / Tetrahedron Letters 48 (2007) 3925–3928
The next stage of our synthetic work was to extend these
results to a Pd-catalyzed olefin insertion reaction, which
was initially developed by Oppolzer et al. and was
proven to be a powerful method for the synthesis of
probably due to a latent ring strain in construction of
a medium-sized ring (entry 5). Under elevated tempera-
ture (110 °C), conjugate diene 5 (17%) was produced
with recovery of 1c (50%) (entry 6).
5
five- and six-membered ring systems. We envisaged that
the olefin insertion reaction of optically active a-alken-
yl-a-acetoxysilane would proceed via the p-allyl palla-
dium intermediate A to produce carbocycle having a
vinylsilane, where the original chirality at the acetoxy
carbon would be transferred to the newly formed chiral
center. Furthermore, in the presence of carbon mono-
xide, palladium would catalyze both olefin insertion and
CO insertion to give a one-carbon homologated cyclic
The present Pd-catalyzed cyclization reaction is charac-
terized by the following points: (1) the reaction of the
(R)-acyloxysilanes gave the (R)-enantiomer of the prod-
uct without any loss of optical purity, (2) carbon–carbon
bond formation occurred exclusively at the c-position to
silicone, and (3) the product had an (E)-vinylsilane moi-
ety. Thus, oxidative addition of Pd(0) into (R)-1a would
occur from the backside of the acetoxy group followed
by coordination to the internal olefin to give optically
active p-allyl palladium intermediates A1 and/or A2
(Scheme 1). The olefin insertion took place at the c-
position to afford r-palladium complexes cis-B and/or
trans-B. Subsequent b-hydride elimination of Pd(II) in
6
product. These results are described in this Letter.
7
According to Oppolzer’s protocol, we examined Pd-
catalyzed cyclization of a-alkenyl-a-acetoxysilanes 1a–c
(
Table 1), prepared in optically active form (Supplemen-
1
4
tary data). Treatment of (R)-1a (n = 1, 92% ee) with
B afforded (R)-2.
Pd(PPh ) (0.1 equiv) and PPh (0.1 equiv) in AcOH
3
4
3
(
degassed) at 85 °C for 1 h underwent olefin insertion
Next, we examined Pd-catalyzed tandem olefin inser-
tion/carbonylation reaction of a-alkenyl-a-acyloxysilane
1a (Scheme 2). Reaction of (R)-1a with Pd(PPh3)4
8
reaction to afford cyclized product 2 having (E)-vinylsil-
ane in 89% yield (entry 1). Optical purity of 2 was deter-
mined to be 92% ee, and its absolute configuration was
R (Supplementary data). Pd-catalyzed cyclization of
(0.1 equiv), PPh (0.1 equiv) and CO (5 atm) at 95 °C
3
for 3 h followed by treatment of the reaction mixture
(
R)-1b (n = 2, 92% ee) required prolonged reaction per-
with H O gave carboxylic acid 6, which, upon esterifica-
2
iod (20 h) under the same reaction conditions to afford
tion with CH N , gave triester 7 (cis:trans = 1:2.3, 88%
2
2
9
–11
six-membered cyclized product 3 (60%)
together with
from 1a). The relative configuration of 7 was confirmed
by the conversion of 6 to a bicyclo[4.3.0]-ring system
(vide infra). The reaction under 1 atm of CO gave a mix-
ture of 7 (70%, cis:trans = 1:2.3) and the non-carbon-
ylated (R)-2 (22% yield, 92% ee) indicating that CO
insertion took place over b-hydride elimination from
cis-B and/or trans-B at higher pressure of CO. Now, it
was clearly understood that cyclization to 2 occurred
from both intermediates cis-B and trans-B via A1 and
A2, respectively, since tandem insertion/carbonylation
reaction gave a mixture of cis-6 and trans-6 (1:2.3), as
shown in Scheme 1. We expected that successive olefin
insertion would occur from intermediate C to give opti-
recovery of 1b (20%) (entry 2). The ee of the starting 1b
1
2
was also completely retained in 3 (92% ee). Using
EtOH or THF as the solvent, conjugate diene 4 was pro-
1
3
duced together with recovery of 1b (entry 3,4). The
reaction of 1c (n = 3) under the standard conditions
resulted in a complete recovery of the starting 1c,
Table 1. Pd-catalyzed olefin insertion of a-alkenyl-a-acetoxysilanes
1a–c
Pd(PPh3)4
0.1 equiv)
n
OAc
n
CO Me
CO Me
(
2
2
TBDMS
CO Me
TBDMS
CO Me PPh3
R
2
R
2
9
2% ee
15
(
0.1 equiv)
cally active bicyclic compounds 9. However, such com-
1
1
1
a: n = 1
b: n = 2
c: n = 3
AcOH, 85 o
2: n = 1
3: n = 2
C
pounds were not obtained in this case, probably due to
the steric hindrance of the TBDMS group, which would
1
6
prevent the olefin coordination.
Substrate Time (h) Product Yield (%)
Recovery of
(%)
1
Construction of
a bicyclo[4.3.0]-ring system was
1
2
3
4
5
6
1a
1b
1
20
22
22
22
6
2
89 (92% ee)
60 (92% ee) 20
—
a
b
achieved by a vinylsilane-terminated cationic cyclization
3
1
7,18
c
e
a
d
of 6 (Scheme 2).
Treatment of the crude reaction
3
30
—
—
—
20
63
f
mixture of 6 with (COCl) (4.5 equiv) in benzene (rt,
3
2
1c
—
—
quant
1 h) followed by treatment with TiCl4 (3 equiv) in
CH Cl (rt, 14 h) gave a separable mixture of unsatu-
g
h
50
2
2
1
9
a
b
c
d
e
f
rated ketones 8 in 31% yield (4 steps from (R)-1a, cis:
trans = 1:2.3). Relative stereochemistry of cis-8 and
trans-8 was determined by the J values (6.3 Hz: cis,
See Ref. 10.
See Ref. 12.
EtOH was used as the solvent.
Diene 4 (39%) was by-produced.
THF was used as the solvent.
Diene 4 (37%) was produced.
10 °C.
20
12.2 Hz: trans) and the NOE experiments (4.0%: cis,
1.5%: trans) of their protons attached to the ring-
junction.
g
1
h
Diene 5 (17%) was produced.
In summary, we have succeeded in construction of opti-
cally active five- and six-membered carbocyclic systems
having a vinylsilane in their side chains by chirality-
transferring Pd-catalyzed intra-molecular olefin inser-
tion of a-alkenyl-a-hydroxysilane, where the starting
n
CO Me
2
TBDMS
CO Me
2
4
5
: n = 2
: n = 3

K. Sakaguchi et al. / Tetrahedron Letters 48 (2007) 3925–3928
3927
O
H
C
AcO
CO Me
2
CO Me
2
Pd
O
CO Me
2
R
CO Me
2
TBDMS
H
TBDMS
AcO
Pd
cis-9
OC
CO Me
2
CO
AcO
Pd
CO Me
2
R
CO2Me
TBDMS
cis-C
R
CO Me
2
TBDMS
H O
2
cis-B
CO Me
2
S
HO C
CO Me
2
TBDMS
CO2Me
2
Pd
AcO
A1
CO Me
2
AcO Pd(II) H
R
TBDMS
cis-6
cis : trans = 1 : 2.3
CO Me
2
OAc
R
CO Me
2
Pd(0)
CO Me
Pd(0) + AcOH
AcO Pd(II) H
R
2
TBDMS
TBDMS
CO Me
2
2
HO C
2
1
a
R
CO Me
2
R
CO Me
2
CO Me
TBDMS
2
TBDMS
CO2Me
trans-6
AcO
Pd
Pd
AcO Pd
H O
2
AcO
A2
CO2Me
CO Me
OC
CO
CO Me
2
R
2
TBDMS
trans-B
R
CO Me
2
TBDMS
trans-C
O
C
H
CO Me
2
CO Me
O
AcO
Pd
2
CO Me
2
R
CO Me
2
TBDMS
H
TBDMS
trans-9
Scheme 1.
1) Pd(PPh3)4 (0.1 equiv)
PPh3 (0.1 equiv)
RO C
CO (5 atm), 95 oC, 3 h
2
OAc
CO Me
CO Me
2
2
CO Me 2) H2O, 45 oC, 1 h
TBDMS
R
TBDMS
CO2Me
2
cis : trans = 1 : 2.3
1
a
92% ee
6
: R = H
CH N
2
2
6
.3 Hz
1
2.2 Hz
NOE
H
.5%
7: R = Me
(88% from 1a)
NOE
4.0%
1
H
O
O
+
1) (COCl)2 (4.5 equiv)
benzene, rt, 1 h
CO Me
R
CO2Me
CO2Me
S
S
2
S
CO Me
2) TiCl4 (3.0 equiv)
CH Cl , rt , 14 h
2
H
H
2
2
1
: 2.3
cis-8
trans-8
3
1% (from (R)-1a)
Scheme 2.
ee was completely transferred to the product. The reac-
tion in the presence of carbon monoxide underwent Pd-
catalyzed olefin insertion–carbonylation reaction to pro-
duce cis and trans five-membered carbocycles having a
carbonylated side chain. Further studies using the pres-
ent chirality-transferring carbon–carbon bond forming
reaction are in progress.
lute configuration of 2; determination of the optical
purity of 3) associated with this article can be found,
in the online version, at doi:10.1016/j.tetlet.2007.03.029.
References and notes
1
2
. Sakaguchi, K.; Higashino, M.; Ohfune, Y. Tetrahedron
003, 59, 6647–6658.
. (a) Sakaguchi, K.; Suzuki, H.; Ohfune, Y. Chirality 2001,
13, 357–365; (b) Morimoto, Y.; Takanishi, M.; Kinoshita,
T.; Sakaguchi, K.; Shibata, K. Chem Commun. 2002, 42–
Acknowledgment
2
This study was financially supported by a Grant-in-Aid
for Scientific Research from the Ministry of Education,
Culture, Sports, Science and Technology, Japan.
4
3; (c) Sakaguchi, K.; Yamamoto, M.; Kawamoto, T.;
Yamada, T.; Shinada, T.; Shimamoto, K.; Ohfune, Y.
Tetrahedron Lett. 2004, 45, 5869–5872.
. Sakaguchi, K.; Yamada, T.; Ohfune, Y. Tetrahedron Lett.
Supplementary data
3
2
005, 46, 5009–5012.
Supplementary data (preparation of cyclization precur-
sor 1a–c; determination of the optical purity and abso-
4. (a) Apeloig, Y.; Stanger, A. J. Am. Chem. Soc. 1985, 107,
2806–2807; (b) Soderquist, J. A.; Hassner, A. Tetrahedron

3928
K. Sakaguchi et al. / Tetrahedron Letters 48 (2007) 3925–3928
Lett. 1988, 29, 1899–1902; (c) Apeloig, Y.; Biton, R.; Bu-
Freih, A. J. Am. Chem. Soc. 1993, 115, 2252–2253.
13. Screening of other Pd-catalysts, ligand and their concen-
tration (Pd(dba) , Pd (dba) –CHCl , and DPPE) did not
improve the yield of 3.
14. Oppolzer, W.; Gaudin, J.-M.; Birkinshaw, T. N. Tetrahe-
dron Lett. 1988, 29, 4705–4708.
2
2
3
3
5
. For reviews, see: (a) Oppolzer, W. Angew. Chem., Int. Ed.
Engl. 1989, 28, 38–52; (b) Oppolzer, W. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Paquette, L.
A., Eds.; Pergamon: Oxford, 1991; Vol. 5, pp 29–61,
Chapter 1.2; (c) Tsuji, J. Palladium Reagents and Cata-
lysts; John Wiley & Sons Ltd: Chichester, 2004; p 483.
. (a) Yamamoto, K.; Terakado, M.; Murai, K.; Miyazawa,
M.; Tsuji, J.; Takahashi, K.; Mikami, K. Chem. Lett.
15. It was reported that the Pd-catalyzed reaction of allyl
acetate 11 (Pd (dba) –CHCl
(0.025 equiv), PPh3
2
3
3
(0.15 equiv), CO (2 atm), AcOH, 80 °C, 20 h) gave not
only five-membered trans-12 (50%) but also additional
olefin-insertion product cis-bicyclo[3.3.0]octane 13 (21%)
6
6
b
1989, 955–958; (b) Terakado, M.; Murai, K.; Miyazawa,
and its trans-isomer (9%). Similar results, see: Yoo,
S.-E.; Lee, S.-H.; Yi, K.-Y.; Jeong, N. Tetrahedron Lett.
1990, 31, 6877–6880.
M.; Yamamoto, K. Tetrahedron 1994, 50, 5705–5718.
. Oppolzer, W.; Gaudin, J.-M. Helv. Chim. Acta 1987, 70,
7
8
1
477–1481.
2
D
1
1
H
H
H
. Compound (R)-2: ½aꢀ +13.9 (c 1.05, CHCl
3
, 92% ee); H
HO C
2
NMR (300 MHz, CDCl
3
) d 5.82 (dd, J = 18.4, 7.1 Hz, 1H),
O
O
AcO
5.68 (d, J = 18.4 Hz, 1H), 4.98 (d, J = 2.0 Hz, 1H), 4.79 (d,
H
2
H
H
J = 2.0 Hz, 1H), 3.74 (s, 3H), 3.72 (s, 3H), 3.17 (m, 1H),
11
1
cis-13
trans-13
3
2
.07 (m, 1H), 2.94 (m, 1H), 2.58 (dd, J = 13.0, 7.7 Hz, 1H),
.03 (dd, J = 13.0, 11.0 Hz, 1H), 0.86 (s, 9H), 0.01 (s, 6H).
1
16. A similar tandem cyclization was completely prevented
when the substrate possessed a vinylic acetoxy group.
Holzapfel, C. W.; Marais, L. Tetrahedron Lett. 1998, 39,
9
. Compound 3: H NMR (300 MHz, CDCl ) d 6.00 (dd,
3
J = 18.7, 7.0 Hz, 1H), 5.70 (dd, J = 18.7, 0.9 Hz, 1H), 4.75
(
d, J = 1.5, 1H), 4.61 (d, J = 1.5 Hz, 1H), 3.78 (s, 3H),
2
179–2182.
3
0
.70 (s, 3H), 2.84 (m, 1H), 2.47–2.32 (4H), 1.83–1.66 (2H),
.87 (s, 9H), 0.02 (s, 6H).
1
1
7. For reviews, see: Blumenkopf, T. A.; Overman, L. E.
Chem. Rev. 1986, 86, 857–873.
8. Burke, S. D.; Murtiashaw, C. W.; Dike, M. S.; Smith
Strickland, S. M.; Saunders, J. O. J. Org. Chem. 1981, 46,
1
1
0. Calculated yield of the reaction mixture by H NMR. The
mixture was composed of 3 and its structural isomers 10
(3:10 = 81:19). The mixture was inseparable by silica-gel
2
400–2402.
chromatographic methods. The structures of 10 were
25
1
1
9. Compound cis-8: ½aꢀ ꢁ101.1 (c 1.30, CHCl
3
); H NMR
tentatively assigned to internal double bond isomers since
D
1
3
(600 MHz, CDCl ) d 6.71 (dd, J = 10.2, 3.3 Hz, 1H), 5.60
H NMR showed signals corresponding to a trans-vinylsi-
(
(
dd, J = 10.2, 1.9 Hz, 1H), 3.74 (s, 3H), 3.70 (s, 3H), 2.95
m, 1H), 2.74 (m, 1H), 2.61 (dd, J = 14.0, 8.4 Hz, 1H),
lane (5.6–6.0 ppm, J = 18.4–18.7 Hz) and an internal olefin.
2
1
.57 (dd, J = 16.7, 5.3 Hz, 1H), 2.54 (dd, J = 14.0, 7.6 Hz,
H), 2.46 (dd, J = 16.7, 5.7 Hz, 1H), 2.42 (dd, J = 14.0,
2
5
TBDMS
CO2Me
CO Me
5.5 Hz, 1H), 2.04 (dd, J = 14.0, 9.2 Hz, 1H). trans-8: ½aꢀ
D
1
2
ꢁ97.0 (c 1.25, CHCl ); H NMR (600 MHz, CDCl ) d
3
3
10
7
1
.04 (dd, J = 9.9, 0.5 Hz, 1H), 6.00 (dd, J = 9.9, 2.6 Hz,
H), 3.75 (s, 3H), 3.74 (s, 3H), 2.79 (dd, J = 12.8, 6.9 Hz,
1
1
1. The yield of a Pd-catalyzed six-membered ring formation
was also moderate (63%), see Ref. 7.
2. Calculated by H NMR using the mixture of the
1H), 2.74 (dd, J = 16.5, 3.6 Hz, 1H), 2.66 (dd, J = 12.8,
6.0 Hz, 1H), 2.41 (m, 1H), 2.20 (dd, J = 16.5, 13.7 Hz,
1H), 2.04 (m, 1H), 1.90 (dd J = 12.8, 6.6 Hz, 1H), 1.88
(dd, J = 12.8, 6.2 Hz, 1H).
1
corresponding MTPA esters (Supplementary data).
Although the absolute configuration of 3 was not
confirmed, it was suggested to be R by consideration of
the result of 2.
20. The J values of the ring-junction protons of both cis-8 and
trans-8 were obtained by the homonuclear decoupling
method.