γ-Trimethylsilyl-substituted allylzirconcenes in organic synthesis. Stereoselective synthesis of terminal 1,3-butadienes and functionalized vinylsilanes

Article abstract of DOI:10.1016/j.tetlet.2004.01.053

γ-Trimethylsilyl-substituted allylzirconcenes, prepared by hydrozirconation of trimethylsilyl-substituted terminal allenes, react with aldehydes at the γ-position to give 1,3-butadienes in one step with good stereoselectivity and undergo conjugate addition to α,β-unsaturated aromatic ketones at the α-position to selectively afford functionalized vinylsilanes in the presence of catalytic CuBr·SMe₂.

Full text of DOI:10.1016/j.tetlet.2004.01.053

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2215–2218
c-Trimethylsilyl-substituted allylzirconcenes in organic synthesis.
Stereoselective synthesis of terminal 1,3-butadienes and
functionalized vinylsilanes
Jin-Hong Pi and Xian Huang*
Department of Chemistry, Zhejiang University, Xi-xi Campus, Hangzhou 310028, PR China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, PR China
Received 18 September 2003; revised 25 December 2003; accepted 5 January 2004
10 Abstract—c-Trimethylsilyl-substituted allylzirconcenes, prepared by hydrozirconation of trimethylsilyl-substituted terminal allenes,
react with aldehydes at the c-position to give 1,3-butadienes in one step with good stereoselectivity and undergo conjugate addition
to a,b-unsaturated aromatic ketones at the a-position to selectively afford functionalized vinylsilanes in the presence of catalytic
CuBrÆSMe2.
Ó 2004 Elsevier Ltd. All rights reserved.
Heteroatom-stabilized allyl organometallics, which can
be used as homoenolate anion synthons and reversed
polarity synthetic equivalents, are of great importance in
20 organic synthesis and a great deal of effort has been
exerted to control the regioselectivity and stereoselec-
tivity in their reactions with electrophiles.1 Silicon-
substituted allylic anions, which can react with a variety
of aldehydes and ketones, are often used to prepare
lactols,2 diols,3 vinylsilanes,4 and terminal 1,3-dienes.5
Organozirconocenes have emerged as one of the most
useful classes of transition metal derivatives for use in
organic synthesis owing to the widely used zirconocene-
mediated tansformations and the relative ease of their
30 preparation.6 In this paper, we wish to report the
condensation reactions of c-trimethylsilyl-substituted
allylzirconcenes with aldehydes to give terminal 1,3-
butadienes in one step and their conjugate additions to
a,b-unsaturated aromatic ketones to afford functiona-
lized vinylsilanes in the presence of catalytic CuBrÆSMe2.
reaction of c-trimethylsilyl-c-butyl-allylzirconcene with
p-anisaldehyde. We found the reaction proceeded
smoothly at )78 °C. To our surprise, the obtained
product was not the expected b-hydroxysilane, as was
the case for various other allylzirconiums,8 Instead the
1,3–terminal butadiene with E configuration was iso-
lated as the major product (Scheme 1).
40
Obviously, c-trimethylsilyl-substituted allylzirconcene 1
reacted with the aldehydes at the c-position, probably
via the chair-like transition state 2, to give 3, this was
Me3Si
Me3Si
Cp2Zr(H)Cl
ZrCp2Cl
C4H9
C4H9
p-CH3OC6H4
c-Trimethylsilyl-substituted allylzirconcenes are easily
prepared by hydrozirconation of trimethylsilyl-substi-
tuted terminal allenes.7 Initially we investigated the
H
C4H9
p-CH3OC6H4CHO
p-CH3OC6H4
//
C4H9
Keywords: Allylzirconcene; Peterson olefination reaction; Conjugation
addition; 1,3-Butadiene; Vinylsilane.
HO
SiMe3
* Corresponding author. Fax: +86-571-8807077; e-mail: huangx@
mail.hz.zj.cn
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.053

2216
J.-H. Pi, X. Huang / Tetrahedron Letters 45 (2004) 2215–2218
followed immediately by the Peterson olefination reac-
tion in a syn manner, which led to the formation of 1,3–
terminal butadiene 4 in one step (Scheme 2).
H
Me3Si
R1CHO
, -78 0
Cp2Cl
ZrCp2Cl
Zr
R1
O
Me3Si
CH2Cl2
C
R
1
With this result in mind, we further investigated the
reactions of different c-trimethylsilyl-substituted allyl-
zirconcenes with different carbonyl compounds and the
results are summarized in Table 1. It shows that in most
cases 1,3-terminal butadiene 4 could be obtained with
good stereoselectivity. However, unsatisfactory results
were obtained when ketones were used and when R was
a more sterically bulky phenyl group, even aldehyde was
used (entry 9). This unusual reactivity in comparison
with the other c-monosubstituted-allylzironiums
reported8 maybe is ascribed to the additional substituted
group on the c-position. Obviously, increasing steric
hindrance could suppress reaction mentioned above.
R
2
ClCp2ZrO
SiMe3
R1
H
syn-elimn.
R1
R
H
R
4
3
Scheme 2.
Recognizing the fact that increasing steric hindrance can
prevent 1 from reacting with the electrophile at the c-
position, we explored its copper-catalyzed addition to
a,b-unsaturated ketones at the a-position (Scheme 3).
Table 1. Stereoselective synthesis of terminal 1,3-butadienes9
R1
Me3Si
R1CHO
ZrCp2Cl
Transmetalation of organic ligands from zirconium to
copper had been intensely researched due to the wide
application of organocopper reagents in synthetic
chemistry. Wipf and Smitrovich reported the first
example of addition of alkyl zirconocenes with catalytic
CuBrÆSMe2 to enones.6 We found in the presence of a
CuBrÆSMe2, allylzirconocene 1 underwent clean conju-
gate addition to a,b-unsaturated ketones when R2 is a
phenyl group at the a-position. The results are sum-
marized in Table 2. The reactions proceeded smoothly
with high stereo and regioselectivity, and the major
products were ðEÞ-vinylsilanes. However, no reaction
result was observed when R2 was an aliphatic group
(entry 9 and 10). Nevertheless, this is, to our knowledge,
the first example of the copper-catalyzed addition of
allylzirconocene to a,b-unsaturated ketones.11
R
H
R
1
4
Entry
R
R1
Product Yield
(%)a
E:Z
ratiob;c
1
2
3
4
5
6
7
8
9
Me
Me
Et
p-BrC6H4
4a
64
62
63
65
71
73
84
86
––
89:11
88:12
90:10
88:12
90:10
91:9
p-CH3OC6H4 4b
p-BrC6H4 4c
p-CH3OC6H4 4d
Et
n-Bu
n-Bu
C6H5
p-CH3OC6H4
4e
4f
C6H5CH2 C6H5
4g
88:12
89:11
––
C6H5CH2 p-CH3OC6H4 4h
C6H5 p-CH3OC6H4 ––
a Isolated yield.
b The isomer ratio was determined by the integration of the 400 MHz
1H NMR spectrum.
c The double-bond geometry of the dienes in Table 1 was determined
by comparing the 1H and 13C NMR spectra of our compounds to
data reported for known compounds and in combination with the
fact that the chemical shift of Ha in isomer A is generally ca. 0.4 ppm
downfield from that of isomer B.10
The stereochemistry of the resulting compounds was
1
established on the basis of H NMR as well as from
NOESY experiments. In the case of 5c, a major triplet at
d 6.12 is attributed to the vinylic hydrogen of the
E-isomer, whereas a minor triplet at d 5.95 was attrib-
uted to the vinylic hydrogen of the Z-isomer. The
assignment of the major signal at d 5.75 to E-isomer is
based on earlier reports that vinylic hydrogens cis-to the
trimethylsilyl group consistently exhibited ca. 0.3 ppm
upfield shift with respect to the corresponding vinylic
hydrogen trans-to the trimethylsilyl group.12 Addition-
ally, there was a strong cross peak between the hydrogen
Ha
Ha
R1
R1
R
R
A
B
O
C
R1
O
C
R2
R1
Me3Si
Me3Si
ZrCp2Cl
R2
.
CuBr SMe2
(15 mol%),
CH2Cl2
R
R
5
1
Scheme 3.

J. -H. Pi, X. Huang / Tetrahedron Letters 45 (2004) 2215–2218
Table 2. CuBrÆSMe2 catalyzed conjugate addition of 1 to a,b-unsaturated ketones13
2217
Entry
R
R1
R2
Product
Yield (%)a
E:Z ratiob
1
2
Et
Et
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
CH3
5a
5b
5c
5d
5e
5f
63
62
68
73
66
65
63
69
––
––
95:5
97:3
98:2
97:3
92:8
93:7
88:12
87:13
––
p-CH3OC6H4
p-CH3C6H4
p-CH3OC6H4
p-BrC6H4
3
n-Bu
n-Bu
4
5
C6H5CH2
C6H5CH2
C6H5
C6H5
C6H5
C6H5
6
p-CH3OC6H4
p-CH3C6H4
C6H5
7
5g
6h
––
––
8
9
10
p-CH3OC6H4
p-CH3OC6H4
CH3CH2
––
a Isolated yield.
b The isomer ratio was determined by the integration of the 400 MHz 1H NMR spectrum.
O
TMS
R2
R2
MPBA
TFA
R
R
R1
O
R1
O
5
6
6a: R = C6H5, R1= p-CH3C6H4, R2 = C6H5 (64%)
6b: R = C2H5, R1= p-CH3OC6H4, R2 = C6H5 (66%)
Scheme 4.
at d 0.08 ppm in the trimethylsilyl group and the
hydrogen at d 5.75 ppm in the NOESY spectrum, which
further supports that the major isomer is the E-isomer.
Acknowledgements
We thank the national natural science foundation of
China for its financial support of the project 20272050.
Vinylsilanes serve as important synthetic intermediates,
and have been converted to other useful compounds in
organic synthesis.14 In order to test the synthetic utility
of the functionalized vinylsilanes 5, we studied their
epoxidation. Epoxidation of 5 with m-chloroperbenzoic
acid, followed by hydrolysis with trifluoroacetic acid in
refluxing methanol afforded 1,6-ketones 6 (Scheme 4).15
In this process, the polarity of the vinylic carbon atom
adjacent to silyl group was reversed, and therefore the
c-trimethylsilyl-substituted allylzirconcene served as
polarity umploung synthetic equivalent 7 (Scheme 5).
References and notes
1. Yamamoto, Y. In Comprehensive Organic Synthesis;
Trost, B., Fleming, I., Eds.; Pergamon: Oxford, 1991;
Vol. II, pp 55–128.
2. Daniels, R. G.; Paquette, L. A. Tetrahedron Lett. 1981, 22,
1579–1582.
3. Tamao, K.; Nakajo, E.; Ito, Y. Tetrahedron Lett. 1988, 44,
3997–4000.
4. Corriu, R. J. P.; Guerin, C.; Mboula, J. Tetrahedron Lett.
1981, 22, 2985–2986.
5. Yamamoto, Y.; Saito, Y.; Maruyama, K. J. Organomet.
Chem. 1985, 292, 311–318.
6. Wipf, P.; Jahn, H. Tetrahedron 1996, 52, 12853–12910.
7. Maeta, H.; Hasegawa, T.; Suzuki, K. Synlett 1993, 341–
343.
8. (a) Maeta, H.; Hasegawa, T.; Suzuki, K. Synlett 1993,
341–343; (b) Chino, M.; Matsumoto, T.; Suzuki, K.
Synlett 1994, 359–361; (c) Suzuki, S.; Hasegawa, T.; Imai,
T.; Maeta, H.; Ohba, S. Tetrahedron 1995, 51, 4483–4494;
(d) Chio, M.; Lianf, G. H.; Matsumoto, T.; Suzuki, K.
Chem. Lett. 1996, 231–232.
In conclusion, we found that c-trimethylsilyl-substituted
allylzirconcenes, prepared by hydrozirconation of tri-
methylsilyl-substituted terminal allenes, react with
aldehydes at the c-position to give 1,3-butadienes in one
step with good stereoselectity. They also undergo con-
jugate addition to a,b-unsaturated aromatic ketones at
the a-position to stereoselectively afford functionalized
vinylsilanes in the presence of catalytic CuBrÆSMe2.
SiMe3
9. General procedure for preparation of 4. Under a nitrogen
a stirred suspension of
O
atmosphere at )78 °C, to
Cp2Zr(H)Cl (2 mmol) in CH2Cl2 (5 mL) was added allene1
(3 mmol) in CH2Cl2 (3 mL). The reaction was gradually
warmed up to room temperature, where a red solution
resulted. The reaction was rechilled to )78 °C, and a
solution of aldehyde (1 mmol) in CH2Cl2 (5 mL) was then
added. After 30 min, the reaction was stopped by adding
R
Zr(Cl)Cp2
R
7
2
Scheme 5.

2218
J.-H. Pi, X. Huang / Tetrahedron Letters 45 (2004) 2215–2218
1611, 1590, 1565, 1485, 860, 750, 695 cmÀ1 1H NMR
.
sat. aq. NaHCO3. Extractive workup was followed by
purification (SiO2 preparative TLC, hexane) giving 4. (b)
Selected data for 4f: IR (neat): 1930, 1875, 1600, 1490,
(400 MHz. CDCl3): d ¼ 7:15–7.99 (m, 9H), 5.75 (t,
J ¼ 6:8 Hz, 1H), 3.47–3.54 (m, 1H), 3.32–3.39 (m, 2H),
2.50–2.67 (m, 1H), 2.44–2.51 (m, 1H), 2.39 ( s, 3H), 2.10–
2.17 ( m, 2H), 1.23–1.40 (m, 4H), 0.97 (t, J ¼ 6:8 Hz, 3H),
0.08 (s, 9H). 13C NMR (100 MHz. CDCl3): d ¼ 199:4,
143.5, 142.1, 137.8, 137.7, 136.1, 133.3, 129.5, 128.9, 128.5,
127.8, 45.0, 41.4, 35.9, 32.8, 30.0, 23.6, 21.4, 14.5, 0.9. MS
(EI): m=z ð%Þ ¼ 392 (3.5). Anal. calcd for C26H36OSi: C,
79.53; H, 9.24. Found: C, 79.54; H, 9.19.
1450, 1410, 1375, 1325, 1175, 1060, 853 cmÀ1 1H NMR
.
(400 MHz. CDCl3): d ¼ 7:18 (d, J ¼ 8:0 Hz, 2H), 6.86 (d,
J ¼ 8:0 Hz, 2H), 6.79 (dd, J ¼ 17:8, 10.8 1H), 6.41 (s, 1H),
5.36 (dd, J ¼ 17:8, 0.8 Hz 1H), 5.15 (dd, J ¼ 10:8, 1 Hz,
1H), 3.80 (s, 3H), 2.35 (t, J ¼ 7:2 Hz, 2H), 1.51–1.59 (m,
2H), 1.37–1.44 (m, 2H), 0.95 (t, J ¼ 6:8 Hz, 3H). 13C
NMR (100 MHz. CDCl3): d ¼ 168:3, 138.1, 134.4, 130.6,
130.2 130.1 128.7 127.8, 114.4, 113.5, 55.2, 33.6, 31.2, 22.8,
14.0. Anal. calcd for C15H20O: C, 83.28; H, 9.32. Found:
C, 83.30; H, 9.37.
14. Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97,
2063–2192.
15. General procedure for preparation of 6. To the solution of
MCPBA (0.33 mmol) in CH2Cl2 (10 mL) was added 5
(0.3 mmol). The mixture was stirred at rt until the
vinylsiane disappeared as determined by TLC. The mix-
ture was washed in turn with sat. aq. NaHCO3, sat. brine,
and water. The solvent solution of TFA (0.33 mmol) in
MeOH (10 mL) was added. After refluxing for 2 h, the
reaction was worked up and a pure product was obtained
by column chromatography (silca gel; ligHt petroleum–
EtOAc, 15:1). (b) Selected data for 6a. IR (neat): 1679,
10. (a) Kise, H.; Sato, T.; Yasuoka, T.; Seno; Asahara, T. J.
Org. Chem. 1979, 44, 4454–4456; (b) Wang, K. K.; Liu, C.;
Gu, Y. G.; Burnett, F. N. J. Org. Chem. 1991, 56, 1914–
1922.
11. Wipf, P. Synthesis 1993, 537–557.
12. Chan, T. H.; Mychajlowakij, W.; Amoroux, R. Tetra-
hedron Lett. 1977, 19, 1605–1608.
13. General procedure for preparation of 5: Under a nitrogen
atmosphere at )78 °C, to
a stirred suspension of
Cp2Zr(H)Cl (2 mmol) in CH2Cl2 (5 mL) was added allene
1 (3 mmol) in CH2Cl2 (3 mL). The reaction was gradually
warmed up to room temperature, where a red solution
resulted. To the resultant mixture was added CuBrÆSMe2
(0.025 mmol) and a,b-unsaturated ketone (1 mmol), and
stirred at rt. This was monitored by TLC, and quenched
with wet Et2O. Extractive workup was followed by
purification (SiO2 preparative TLC, hexane–EtOAc 10:1)
giving 5. (b) Selected data for 5c: IR (neat): 1690, 1665,
1596, 1579, 823, 746, 689 cmÀ1 1H NMR (400 MHz.
.
CDCl3): d ¼ 7:09–7.94 (m, 14H), 3.40–3.47 (m, 1H), 3.33–
3.35 (m, 2H), 2.90–2.99 (m, 1H), 2.75–2.83 (m, 1H), 2.30
(s, 3H), 2.20–2.28 (m, 1H), 2.03–2.13 (m, 1H). 13C NMR
(100 MHz. CDCl3): d ¼ 200:0, 198.8, 140.8, 137.1, 136.9,
136.1, 132.9, 132.8, 129.3, 128.5, 128.0, 127.9, 127.5, 46.2,
40.3, 36.8, 30.6, 210. MS (EI): m=z ð%Þ ¼ 357 (76.5), 105
(100). Anal. calcd for C25H24O2: C, 84.24; H, 6.79. Found:
C, 84.27; H, 6.84.