Palladium-catalyzed allylic alkylation of optically active α-alkenyl-α-acyloxytrialkylsilane

Article abstract of DOI:10.1016/j.tetlet.2005.05.076

Pd-catalyzed inter- and intramolecular allylic alkylations of optically active α-alkenyl-α-acyloxysilanes are described. The reactions proceeded in a regio- and stereoselective manner to give the corresponding (E)-vinylsilanes in which the ee of the start

Full text of DOI:10.1016/j.tetlet.2005.05.076

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 5009–5012
Palladium-catalyzed allylic alkylation of optically active
a-alkenyl-a-acyloxytrialkylsilane
Kazuhiko Sakaguchi,* Takeshi Yamada and Yasufumi Ohfune*
Graduate School of Science, Department of Material Science, Osaka City University, Sugimoto, Sumiyoshi, Osaka 558-8585, Japan
Received 20 April 2005;revised 16 May 2005;accepted 19 May 2005
Available online 13 June 2005
Abstract—Pd-catalyzed inter- and intramolecular allylic alkylations of optically active a-alkenyl-a-acyloxysilanes are described. The
reactions proceeded in a regio- and stereoselective manner to give the corresponding (E)-vinylsilanes in which the ee of the starting
material was completely transferred to the product.
Ó 2005 Elsevier Ltd. All rights reserved.
OAc
Nu
During the course of our recent studies regarding the
syntheses and reactions of optically active a-hydroxy-
silane,1 we found that an acidic treatment of a-alkenyl-
a-hydroxysilane (>95% ee) proceeded through a puta-
tive a-silyl cation2 to give a rearranged c-hydroxyvi-
nylsilane with partial racemization (27% ee) (Eq. 1).3
These results prompted us to examine a chirality-trans-
ferring carbon–carbon bond formation via the chiral
cationic complex, which can be generated from a-alke-
nyl-a-acyloxysilane as a p-allyl palladium complex
(Eq. 2). It is of interest to examine the regioselectivity
upon alkylation and the extent of the chirality transfer.
In this letter, we describe highly enantio- and regio-
selective inter- and intramolecular Pd-catalyzed allylic
alkylations of a-alkenyl-a-acyloxysilanes with carbon
nucleophiles.4
TBDMS
TBDMS
*
OAc
*
EWG
Nu
or
base
L
L
Pd(0)
Pd
EWG
TBDMS
*
OAc
EWG
EWG
TBDMS
TBDMS
*
n
n = 0, 1
TBDMS
*
π-allyl palladium
complex
n+3
α-alkenyl-α-acyloxysilane
chirality transfer ?
regioselectivity ?
ð2Þ
Initially attempted was an intermolecular Pd(0)-cata-
lyzed allylic alkylation of optically active a-acyloxy-
silane 1.5 Reaction of (R,E)-1 (90% ee)3 with dimethyl
malonate (4.2 equiv) under our standard reaction condi-
tion {NaH (4.2 equiv), Pd(PPh3)4 (0.13 equiv), and PPh3
(0.1 equiv) under reflux in THF for 4 h} (method A)
promoted intermolecular alkylation to give (E)-vinyl-
silane 2 in 84% yield (Scheme 1). The ee of the product
was 90%, and its absolute configuration was R (Supple-
mentary data).6 Thus, we found that not only the optical
purity of the starting material was completely trans-
ferred to the product but also the reaction occurred
exclusively at c to Si and the products had (E)-olefin.
These results suggested that the allylic alkylation of
TBDMS
OH
α
OH
H
TBDMS
TBDMS
27% ee
*
*
>95% ee
optically active
α-hydroxysilane
TBDMS
γ
γ
partial transfer of chirality
α
chiral
α,γ-silylallyl cation
TBDMS = t-BuMe2Si
TBDMS
ð1Þ
MeO2C
CO2Me
CH2(CO2Me)2 (4.2 equiv)
NaH (4.2 equiv)
OAc
TBDMS
TBDMS
(R,E)-2
84%
Pd(PPh3)4 (0.13 equiv)
PPh3 (0.1 equiv)
THF, reflux, 4 h
90% ee
(R,E)-1
90% ee
Keywords: Pd-catalyzed allylic alkylation; a-Acyloxysilane; a-Silyl
cation;Chirality transfer.
(method A)
*
Corresponding authors. Tel.: +81 6660 52571;fax: +81 6660
52522;e-mail: sakaguch@sci.osaka-cu.ac.jp
Scheme 1.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.05.076

5010
K. Sakaguchi et al. / Tetrahedron Letters 46 (2005) 5009–5012
Nu
MeO2C
CO2Me
OAc
inversion
γ
Pd(0)
α
TBDMS
(R,E)-1
TBDMS
TBDMS
inversion
a
Pd
(R,E)-2
retention
L
L
inversion
L
path a: net retention
path b, c: net inversion
L
Pd
TBDMS
Pd
TBDMS
L
Nu
c
syn-oxidative
Nu
addition
retention
Pd(0)
b
Nu
a
MeO2C
CO2Me
a
OAc
α
Pd(0)
γ
TBDMS
inversion
TBDMS
anti-oxidative
TBDMS
(R,Z)-1
a,c
Pd
(S,E)-2
L
L
addition
inversion
c
Nu
Scheme 2.
a-acyloxysilane 1 with Pd(PPh3)4 proceeded through an
inversion–inversion (net retention) mechanism via a p-
allyl palladium intermediate in the same manner as that
of a conventional Pd(0)-catalyzed allylic alkylation
(path a, Scheme 2).7 The c-regioselectivity would be ex-
plained by both (1) steric effect, that is, a sterically bulky
TBDMS group compared to a methyl group (a:c =
< 1:>99), and (2) electric character, that is, the more
electrophilic property of c-carbon than that of a-
carbon.8
product, without loss of its optical purity.6 We screened
the reaction by changing the substrate, amount of the
phosphine ligand, and the solvent as summarized in
the following: (1) (R,E)-1 gave a net retention product
(R,E)-2 (entry 3), (2) with increased amount of PPh3,
the product ee was decreased (entries 4 and 5) and the
product configuration was inversed to S by the addition
of 0.33 equiv of PPh3 (entry 6), while without PPh3 gave
rise to (S,E)-2 (entry 7),9 (3) the use of CH3CN as the
solvent gave a net retention product (S,E)-2 in 87% yield
with 92% ee (entry 8) in contrast to the use of THF in
entry 2.10 To the fact that the reaction of (R,Z)-1 using
method B (0.04 equiv of PPh3 in THF) gave a net inver-
sion product (R,E)-2, it would be produced via internal
syn-oxidative addition of Pd(0)11 (retention) and subse-
quent attack of the nucleophile from the backside of
the Pd atom (inversion) (path b) as shown in Scheme
2. The reaction with an increased amount of PPh3 would
proceed through paths a and b in a competitive manner.
An alternative mechanism that involves a transmetala-
tion followed by an internal delivery of the nucleophile
We next examined the reaction of the (Z)-isomer of the
a-acyloxysilane 1 (>95% ee)3 under the same reaction
conditions. However, the reaction was quite slow
(23 h) and gave (S,E)-vinylsilane (38%, >95% ee) along
with recovery of the starting 1 (52%, >95% ee) (Table
1, entry 1). To improve the yield of the reaction,
Pd2(dba)3–CHCl3 was employed as a catalyst (method
B). The reaction under the standard conditions gave
an increased yield of (E)-2 (entry 2). However, the prod-
uct possessed an R configuration that of a net inversion
Table 1. Pd-catalyzed allylic alkylation of a-acyloxyallylsilane 1
Pd(0) (cat.), PPh3,
CH2(CO2Me)2 (4.2 equiv)
(E)-2
(R)-1
NaH (4.2 equiv)
THF, reflux
Entry
(R)-1a
Methodb
PPh3 (equiv)
Time (h)
(E)-2
Yield (%)
ee (%)
Recovery of 1 (%)d
1
2
3
4
5
6
7
8c
Z
Z
E
Z
Z
Z
Z
Z
A
B
B
B
B
B
B
B
0.1
23
23
4
S
R
R
R
R
S
S
S
38
67
86
40
62
41
6
>95
>95
73
52
27
0
0.04
0.04
0.08
0.16
0.33
None
0.04
23
23
23
23
23
65
38
51
31
40
78
6
24
19
87
92
a (R,E)-1 (90% ee), (R,Z)-1 (>95% ee).
b Method A: Pd(PPh3)4 (0.13 equiv), CH2(CO2Me)2 (4.2 equiv), NaH (4.2 equiv), THF, reflux. Method B: Pd2(dba)3–CHCI3 (0.04 equiv),
CH2(CO2Me)2 (4.2 equiv), NaH (4.2 equiv), THF, reflux.
c CH3CN, 90 °C.
d In each case, the recovered 1 retained the optical purity of the starting 1.

K. Sakaguchi et al. / Tetrahedron Letters 46 (2005) 5009–5012
5011
CO2Me
AcO
Pd(II)
MeO2C
R
TBDMS
TBDMS
TBDMS
6
OAc
CO2Me
CO2Me
(S)-4
condition
TBDMS
4
AcO
(R)-3b 86% ee
β-elimination
Pd(II)
R
TBDMS
R
5
CO2Me
CO2Me
7
AcO-Pd(II)-H
R =
reductive
elimination
3
Pd(0) + AcOH
Condition: Pd(PPh3)4 (0.1 equiv), PPh3 (0.1 equiv), NaH, reflux, 14 h
NaH
(equiv)
(S)-4 (% ee)
(%)
5
(%)
entry
solvent
1
1.0
2.0
2.0
2.0
33 (87) 27
THF
THF
THF
DMFb
2
37 (c)
55 (c)
84 (87)
0
0
0
3a
4a
a) Pd2(dba)3-CHCl3 (0.05 equiv), PMePh2
(0.3 equiv). b) 100 oC, 3 h. (c) Not detected.
Scheme 3.
from the p-allyl-Pd complex generated by anti-oxidative
addition (path c) is less likely under the reaction condi-
tions because the transmetalation does not generally
proceed in the case of soft nucleophile such as malonate
anion.4 The use of a polar solvent would accelerate path
a to give (S,E)-2.11 Thus, it was found that each enantio-
mer could be prepared in good yields by the use of
Pd2(dba)3–CHCl3 in THF or CH3CN.
was a suitable combination to give 4 in 55% yield (entry
3).15 Finally, the reaction was optimized by the use of
DMF (100 °C) as the solvent. The reaction was com-
pleted within 3 h to give (S)-4 in 84% yield (87% ee)
(entry 4).16 This would be due to high solubility of the
reactant in DMF since the use of benzene (18%) or ace-
tonitrile (13%) resulted in low yields, respectively.17
Reaction of (R)-3a (n = 3, 86% ee) under the optimized
conditions afforded five-membered product (S)-8 (88%
ee) in 78% yield (Scheme 4).13 On the other hand, reac-
tion of 3c (n = 5) gave only a trace amount of cyclized
product 9,18 probably due to a latent ring strain in a
medium-size ring. These results suggested that the pres-
ent Pd(0)-catalyzed reaction would undergo an intramo-
lecular allylic alkylation of a-alkenyl-a-acyloxysilane via
a conventional net retention pathway through a p-allyl
palladium intermediate.
Next, we turned our attention to an intramolecular
Pd(0)-catalyzed allylic alkylation of a-acyloxyallylsilane
toward the construction of optically active carbocy-
cles.12 Three cyclization precursors 3a–c (n = 3, 4, and
5) were synthesized in optically active forms except for
n = 5 (Supplementary data). As a preliminary experi-
ment, (R)-3b n = 4 was treated with NaH, Pd(PPh3)4,
and PPh3 in THF (Scheme 3). The reaction gave the
esired six-membered carbocycle 4 having (E)-vinylsi-
lane,13 while the yield was low (33%) and diene 5
(27%) was a by-product (entry 1). The optical purity
of the starting material was completely transferred to 4
(87% ee), and its absolute configuration was S (a net
retention product, Supplementary data). Next, we
attempted to optimize the reaction conditions relative
to (1) amount of NaH, (2) other Pd catalysts, (3) effect
of phosphine ligand, and (4) solvent. It was considered
that in situ generated AcOH would accelerate b-elimina-
tion of the Pd(II) species in the g1-allyl palladium(II)
intermediate 7 to give diene 5. The use of excess NaH
would eliminate such reaction pathway. Indeed, the
use of 2 equiv of NaH did not give the diene at all,
but the yield of 4 was not satisfactory (entry 2).14 To
increase the yield of the cyclized product, we screened
several phosphine ligands and Pd catalysts. The use of
Pd2(dba)3–CHCl3 (0.05 equiv) and PMePh2 (0.3 equiv)
In summary, Pd(0)-catalyzed allylic alkylations of opti-
cally active a-alkenyl-a-acyloxysilanes were examined.
The reaction proceeded in a stereo- and regioselective
manner to give the corresponding acyclic and cyclic
CO2Me
MeO2C
TBDMS
OAc
CO2Me
4 h
TBDMS
CO2Me
3
78%
(S)-8
88% ee
CO2Me
(R)-3a
86% ee
MeO2C
OAc
CO2Me
19 h
TBDMS
CO2Me
racemic
TBDMS
5
trace
3c
9
Scheme 4. Reagents and conditions: Pd2(dba)3–CHCl3 (0.05 equiv),
PMePh2 (0.3 equiv), NaH (2 equiv), DMF, 100 °C.

5012
K. Sakaguchi et al. / Tetrahedron Letters 46 (2005) 5009–5012
3H), 3.33 (d, J = 9.2 Hz, 1H), 2.97 (dqd, J = 9.2, 6.8,
6.8 Hz, 1H), 1.08 (d, J = 6.8, 3H), 0.83 (s, 9H), 0.01 (s,
3H), ꢁ0.02 (s, 3H).
(E)-vinylsilanes. The products completely retained the
optical purity of the starting materials. Thus, a novel
chiral a- or c-silyl cation species was trapped as a p-allyl
palladium intermediate. Further studies using the pres-
ent chirality-transferring carbon–carbon bond forming
reaction are in progress.
7. (a) Trost, B. M.;Verhoeven, T. R. J. Am. Chem. Soc.
1980, 102, 4730–4743;(b) Frost, C. G.;Howarth, J.;
Williams, J. M. J. Tetrahedron: Asymmetry 1992, 3, 1089–
1122.
8. According to the MP2/6-31G*//3-21G calculations, car-
bocation a to the SiH3 group is 18.3 kcal/mol less stable
than the corresponding carbocation a to a methyl group.2a
9. As a control experiment, the reaction of (R,Z)-1 (>95% ee)
using method B without carbon nucleophile resulted in a
formation of 1-TBDMS-1,3-butadiene with a recovery of
(R,Z)-1 (>95% ee). This also suggests the present reaction
proceeds through a p-allyl palladium(II) intermediate in
Scheme 3.
10. The (R,Z)-a-acyloxysilane 1 (>95% ee) was converted to
(S,E)-vinylsilane 2 (>95% ee) via Pd(II)-catalyzed allylic
rearrangement in two steps (67%) by PanekÕs protocol:
Panek, J. S.;Sparks, M. A. J. Org. Chem. 1990, 55, 5564–
5566.
Acknowledgements
We thank a referee for a useful suggestion about the
reaction mechanism. This study was financially sup-
ported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science,
and Technology, Japan, and a Grant from Suntory
Institute for Bioorganic Research (SUNBOR).
Supplementary data
11. Kurosawa, H.;Kajimaru, H.;Ogoshi, S.;Yoneda, H.;
Miki, K.;Kasai, N.;Murai, S.;Ikeda, I.
Soc. 1992, 114, 8417–8424.
J. Am. Chem.
Supplementary data associated with this article can be
found, in the online version at doi:10.1016/j.tetlet.
2005.05.076.
12. Intramolecular Pd-catalyzed allylic alkylation, see: (a)
Trost, B. M.;Verhoeven, T. R. J. Am. Chem. Soc. 1980,
102, 4743–4763;(b) Takahashi, T.;Jinbo, Y.;Kitamura,
K.;Tsuji, J. Tetrahedron Lett. 1984, 25, 5921–5924;(c)
Yamamoto, K.;Deguchi, R.;Ogimura, Y.;Tsuji, J. Chem.
Lett. 1984, 1657–1660;(d) Trost, B. M. Angew. Chem., Int.
Ed. Engl. 1989, 28, 1173–1192;(e) Heumann, A.;Reglier,
M. Tetrahedron 1995, 51, 975–1015.
References and notes
1. (a) Sakaguchi, K.;Mano, H.;Ohfune, Y.
Tetrahedron
Lett. 1998, 39, 4311–4312;(b) Sakaguchi, K.;Fujita, M.;
Ohfune, Y. Tetrahedron Lett. 1998, 39, 4313–4316;(c)
Sakaguchi, K.;Fujita, M.;Suzuki, H.;Higashino, M.;
Ohfune, Y. Tetrahedron Lett. 2000, 41, 6589–6592;(d)
Sakaguchi, K.;Suzuki, H.;Ohfune, Y. Chirality 2001, 13,
357–365;(e) Morimoto, Y.;Takanishi, M.;Kinoshita, T.;
Sakaguchi, K.;Shibata, K. Chem Commun. 2002, 42–43;
(f) Sakaguchi, K.;Yamamoto, M.;Kawamoto, T.;Yam-
24
13. (S)-4: ½aꢀD ꢁ32.7 (c 0.64, CHCl3, 87% ee); 1H NMR
(400 MHz, CDCl3) d 6.25 (dd, J = 18.6, 8.5 Hz, 1H), 5.63
(d, J = 18.6 Hz, 1H), 3.67 (s, 3H), 3.66 (s, 3H), 2.78 (dt,
J = 12.0, 4.0 Hz, 1H), 2.15 (m, 1H), 1.97 (m, 1H), 1.80 (m,
1H), 2.78–1.53 (2H), 1.50–1.34 (3H), 0.84 (s, 9H), ꢁ0.01
18
(s, 3H), ꢁ0.03 (s, 3H). (S)-8: ½aꢀD ꢁ59.1 (c 1.51, CHCl3,
88% ee); 1H NMR (400 MHz, CDCl3) d 5.96 (dd, J = 18.6,
7.3 Hz, 1H), 5.71 (dd, J = 18.6, 1.2 Hz, 1H), 3.72 (s, 3H),
3.62 (s, 3H), 3.29 (dt, J = 7.2, 7.2 Hz, 1H), 2.47 (dt,
J = 13.7, 8.3 Hz, 1H), 2.08 (ddd, J = 13.8, 9.0, 4.8 Hz, 1H),
1.99–1.81 (2H), 1.75–1.50 (2H), 0.84 (s, 9H), ꢁ0.02 (s,
6H).
ada, T.;Shinada, T.;Shimamoto, T.;Ohfune, Y.
hedron Lett. 2004, 45, 5869–5872.
Tetra-
2. Several reports regarding the stability of a-silyl cation, see:
(a) Apeloig, Y.;Stanger, A. J. Am. Chem. Soc. 1985, 107,
2806–2807;(b) Soderquist, J. A.;Hassner, A. Tetrahedron
Lett. 1988, 29, 1899–1902;(c) Apeloig, Y.;Biton, R.;
bu-Freih, A. J. Am. Chem. Soc. 1993, 115, 2252–2253.
3. Sakaguchi, K.;Higashino, M.;Ohfune, Y. Tetrahedron
2003, 59, 6647–6658.
4. Reviews for Pd-catalyzed allylic alkylations, see: (a) Trost,
B. M.;Verhoeven, T. R. In Comprehensive Organometallic
Chemistry;Pergamon Press, 1982;Vol. 8, p 799;(b)
Godleski, S. A. In Comprehensive Organic Synthesis;
Pergamon Press, 1999;Vol. 4, p 585;(c) Tsuji, J. Palladium
Reagent and Catalysts;John Wiley & Sons: Chichester,
2004, p 431.
14. The reaction using a carbonate instead of acetate without
a base under the same conditions did not proceed at all,
while heating under reflux for 7 h gave diene 5 (34%). The
use of 2 equiv of NaH gave a mixture of 4 (24%) and 5
(10%) when heated under reflux for 7 h.
15. The use of DPPE, DPPB, or DPPF gave 4 in 44%, 46%,
and 38%, respectively. On the other hand, P(n-Bu)3,
P(Cy)3, PMe2Ph, P(o-tol)3, AsPh3, or DPPP by-produced
the diene 5.
16. The reaction of 3b using Pd(PPh3)4 and PPh3 without a
base (THF, reflux, 14 h) gave the diene 5 in 92% yield;
however, the reaction using Pd2(dba)3–CHCl3 (0.05 equiv)
and PMePh2 (0.05 equiv) (DMF, 100 °C, 19 h) gave 5
(32%) with recovery of 3b (56%).
17. Using DMF as the solvent, the reaction of 3b with
Pd(PPh3)4 (0.1 equiv) and PPh3 (0.1 equiv) instead of
Pd2(dba)3–CHCl3 and PMePh2 gave 4 (72%) as the sole
product.
5. Pd-catalyzed allylic alkylation of silicon-containing sub-
strate, see: (a) Hirao, T.;Enda, J.;Ohshiro, Y.;Agawa, T.
Tetrahedron Lett. 1981, 22, 3079–3080;(b) Commandeur,
C.;Thorimbert, S.;Malacria, M. J. Org. Chem. 2003, 68,
5588–5592.
20
6. (R)-2: ½aꢀD ꢁ19.3 (c 1.14, CHCl3, 90% ee, from (R,E)-1);
20
½aꢀD ꢁ25.9 (c 1.05, CHCl3, >95% ee, from (R,Z)-1); 1H
NMR (300 MHz, CDCl3) d 5.93 (dd, J = 18.6, 7.4 Hz,
1H), 5.70 (dd, J = 18.6, 0.8 Hz, 1H), 3.72 (s, 3H), 3.67 (s,
18. Trace amounts of diene were detected from the crude
product by H NMR.
1