Highly stereospecific, palladium-catalyzed cross-coupling of alkenylsilanols

Article abstract of DOI:10.1021/ol005565e

(Formula presented) Alkenylsilanols bearing methyl ((E)-1 and (Z)-1) or isopropyl ((E)-2 and (Z)-2)) substituents are converted to disubstituted alkenes by a palladium-(0)-catalyzed cross-coupling reaction with aryl or vinyl iodides in the presence of tet

Full text of DOI:10.1021/ol005565e

ORGANIC
LETTERS
2
000
Vol. 2, No. 4
65-568
Highly Stereospecific,
Palladium-Catalyzed Cross-Coupling of
Alkenylsilanols
5
Scott E. Denmark* and Daniel Wehrli
Roger Adams Laboratory, Department of Chemistry, UniVersity of Illinois,
600 South Mathews AVenue, Urbana, Illinois 61801
denmark@scs.uiuc.edu
Received January 18, 2000
ABSTRACT
Alkenylsilanols bearing methyl ((E)-1 and (Z)-1) or isopropyl ((E)-2 and (Z)-2)) substituents are converted to disubstituted alkenes by a palladium-
0)-catalyzed cross-coupling reaction with aryl or vinyl iodides in the presence of tetrabutylammonium fluoride or hydroxide. Yields and
stereoselectivities are generally high, and the reaction is compatible with a wide range of functional groups.
(
The importance of metal-catalyzed, cross-coupling reactions
for the construction of carbon-carbon bonds between
unsaturated centers is unparalleled. The extraordinary di-
versity of organometallic nucleophiles and organic electro-
philes that have been enlisted into useful service is testimony
to the continuing interest in identifying milder procedures
the utility of alkenyl- and arylsilacyclobutanes for mild and
stereospecific cross-coupling reactions has been docu-
4
mented. These agents demonstrate significant practical
advantages when compared to other silicon-based methods
in ease of preparation, mildness of reaction conditions, and
stereospecificity.
1
and broader structural generality for this transformation. Of
As part of our continuing efforts to identify other simple
silicon derivatives capable of engaging in mild cross-coupling
processes, we have found that silanols and disiloxanes are
also competent in effecting this transformation under condi-
tions nearly identical to those employed for the alkenyl-
paramount importance in developing new cross-coupling
reactions are the following: (1) ease of preparation of the
organic “donor”, (2) mildness of reaction conditions, (3)
stereospecificity, (4) functional group compatibility, and (5)
tractability of byproducts.
5
silacyclobutanes. In this Letter, we disclose the preparation
While organosilicon compounds could, in principle, rep-
resent ideal coupling partners, only in recent years have
practical procedures been developed that address, in part,
the invention criteria outlined above. Among the most notable
and cross-coupling of geometrically defined alkenylsilanols
with a variety of aryl and alkenyl iodides.
To make direct comparisons to the previously described
cross-coupling with alkenylsilacyclobutanes, we chose to
examine the geometrically defined (1-heptenyl)-dimethyl-
silanols (E)-1 and (Z)-1 and (1-heptenyl)-di(isopropyl)silanols
6
2
3a
are aryl- and/or alkenylfluorosilanes, -fluorosiliconates, and
3b
-
orthosiliconates. In two recent reports from this laboratory,
(
E)-2 and (Z)-2. These substrates could be easily prepared
(
1) (a) Diederich, F., Stang, P. J., Eds. Metal-Catalyzed Cross-Coupling
by following established procedures as outlined in Schemes
1
Reactions; Wiley-VCH: Weinheim, 1998. (b) Heck, R. F. Palladium
Reagents in Organic Syntheses; Academic Press: New York, 1985. (c) Tsuji,
I. Palladium Reagents and Catalysts. InnoVations in Organic Synthesis;
Wiley: Chichester, U.K., 1995.
5
b,7
8
and 2. Thus, treatment of (E)-1-bromo-1-heptene with
(
2) (a) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845. (b) Hiyama, T. In
(3) (a) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 3266. (b)
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, 1998; Chapter 10. (c) Horn, K. A. Chem. ReV.
995, 95, 1317.
Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684.
(4) (a) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821.
(b) Denmark, S. E.; Wu, Z. Org. Lett. 1999, 1, 1495.
1
1
0.1021/ol005565e CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/01/2000

stereoisomer (Z)-2 was produced by a high-yielding, three-
9
step synthesis starting from (Z)-1-iodo-1-heptene. Lithium-
Scheme 1
iodide exchange with n-butyllithium, followed by the addition
of chlorodi(isopropyl)silane, formed the intermediate (1-
heptenyl)di(isopropyl)silane in 95% yield. Oxidation with
4
chlorine (0.9 M solution in CCl ), followed by mild hy-
drolysis, produced (Z)-2 in 90% yield over two steps.10
With the requisite silanols in hand, we next investigated
their ability to undergo palladium(0) catalyzed cross-
couplings. The extensive optimization of reaction conditions
(palladium catalyst, fluoride source, stoichiometry, solvent,
and temperature) already carried out in the context of the
silacyclobutane coupling provided an ideal starting point for
these studies. Accordingly, the silanol was first combined
with tetrabutylammonioum fluoride (TBAF) in THF for 10
min at room temperature, followed by the addition of the
tert-butyllithium, followed by the addition of hexamethyl-
cyclotrisiloxane, resulted in the formation of (E)-1 in 74%
yield. The corresponding Z-isomer was prepared in a similar
9
manner from (Z)-1-iodo-1-heptene which upon treatment
2
organic iodide and the palladium complex (Pd(dba) ). We
with n-butyllithium and hexamethylcyclotrisiloxane afforded
Z)-1 in 68% yield.10
were delighted to discover that the reactions were generally
complete within 10-30 min (Table 1). Again following the
lessons from previous studies, the product was separated
from, inter alia, polysilicone byproducts by a three-step
procedure: (1) filtration of the reaction mixture through a
plug of silica gel, (2) column chromatography (silica gel or
reverse phase C18), and (3) distillation. These conditions
differ from those employed for silacyclobutanes only in the
amount of TBAF added. It was shown that only 2 equiv of
a freshly prepared TBAF solution was enough to effectively
promote the cross-coupling of silanols within 10 min.
With silacyclobutanes it was observed that the reactions
stalled at ca. 85% conversion when less than 3 equiv of a
commercially available THF solution of TBAF (1 M) was
used; however, this was later found to be dependent on the
(
To investigate the influence of the nontransferable groups
on the silicon atom (and illustrate an alternative entry to the
silanol precursors), we also prepared di(isopropyl)silanols
2 6
(E)-2 and (Z)-2 (Scheme 2). Catalytic (H PtCl ) hydrosily-
Scheme 2
1
2
quality of the TBAF employed. Further reduction in the
amount the TBAF, however, resulted in a decrease in the
reaction rate and yield (cf. entries 8 and 9 in Table 1).
The fluoride is required, however, as omission of TBAF
from the reaction mixtures resulted in complete recovery of
lation of 1-heptyne with chlorodi(isopropyl)silane followed
1
3
both the aryl iodide and the silanol.
1
0,11
by alkaline hydrolysis provided (E)-2 in 78% yield.
The
We have discovered that while a basic/nucleophilic activa-
tor is essential, it need not be fluoride. Substitution of
tetrabutylammonium fluoride with the hydroxide (as a 2.0
M solution in methanol) gave rise to a comparable rate and
yield for the coupling of (E)-1 with 1-iodonaphthalene (cf.
entries 3 and 5, Table 1). However, the product is ac-
companied by 2.5% of the cine rearrangement product.
The similarity in rate and yield for the cross-coupling of
silacyclobutanes and dimethylsilanols was indeed satisfying.
Selectivities obtained with the dimethylsilanols were slightly
lower than those observed with the silacyclobutanes; up to
(
5) For recent reports on the preparation and synthetic transformations
of silanols, see: (a) Lickiss, P. D. AdV. Inorg. Chem. 1995, 42, 147. (b)
Hirabayashi, K. Takahisa, E.; Nishihara, Y.; Mori, A.; Hiyama, T. Bull.
Chem. Soc. Jpn. 1998, 71, 2409. (c) Hirabayashi, K.; Nishihara, Y.; Mori,
A.; Hiyama, T. Tetrahedron Lett. 1998, 39, 7893. (d) Chan, T. H.; Chen,
L. M.; Wang, D. J. Chem. Soc., Chem. Commun. 1988, 1280. (d) Chan, T.
H.; Chen, L. M.; Wang, D.; Li, L. H. Can. J. Chem. 1993, 71, 60 (e)
Yamamoto, K.; Kawanami, Y.; Miyazawa, M. J. Chem. Soc., Chem.
Commun. 1993, 436. (f) Li, L. H.; Chan, T. H. Tetrahedron Lett. 1997, 38,
01. (g) Takaku, K.; Shinokubo, H.; Oshima, K. Tetrahedron Lett. 1996,
7, 6781. (h) Takaku, K.; Shinokubo, H.; Oshima, K. Tetrahedron Lett.
997, 38, 5189. (i) Uehara, S.; Takaku, H.; Shinokubo, K.; Oshima, K.
Synlett 1998, 1096. (j) Trost, B. M.; Ito, N.; Greenspan, P. D. Tetrahedron
Lett. 1993, 34, 1421. (k) Soderquist, J. A.; Vaquer, J.; Diaz, M. J.; Rane,
A. M.; Bordwell, F. G.; Zhang, S. Tetrahedron Lett. 1996, 37, 2561. (l)
Akiyama, T.; Imazeki, S. Chem. Lett. 1997, 1077.
1
3
1
(10) Silanols (E)- and (Z)-1 and (E)- and (Z)-2 were all obtained in
geometrically pure form (>99%), as established by capillary GC analysis.
(11) Miller, R. B.; McGarvey, G. J. Org. Chem. 1978, 43, 4424.
(12) 1 M TBAF solutions were prepared from commercially available
(6) Hiyama has recently described the palladium-catalyzed cross-coupling
of aryl- and (E)-alkenylsilanols with aryl halides in the presence of 200
mol % of silver(I) oxide. These reactions required 36 h at 60 °C and may
also be mechanistically distinct from the couplings described herein.
Hirabayashi, K.; Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Org.
Lett. 1999, 1, 299.
1
9
crystalline TBAF and freshly distilled THF. Analysis by F NMR
spectroscopy showed one single signal at -115.9 ppm (vs CFCl3). The
commercially available 1 M solution contained more than five different
signals in the 19F NMR spectrum. Silacyclobutanes could be cross-coupled
in high yields and conversions, using only 2 equiv of the freshly prepared
TBAF solution.
(7) (a) Sieburth, S. McN.; Mu, W. J. Org. Chem. 1993, 58, 6314. (b)
Sieburth, S. McN.; Fensterbank, L. J. Org. Chem. 1993, 58, 7584.
(
(
8) Kropp, P. J.; Crawford, S. D. J. Org. Chem. 1994, 59, 3102.
9) Ravid, U.; Silverstein, R. M.; Smith, L. R. Tetrahedron 1978, 34,
(13) The silanol is partly converted into the disiloxane during isolation;
however mass balance accounts for 93% of the initially employed silanol.
1
449.
566
Org. Lett., Vol. 2, No. 4, 2000

Table 1. Palladium-Catalyzed Cross-Coupling of (E)-1 and (Z)-1 with Aryl Iodidesa
R1
R2
aryl
time, min
product
yield, %
b
ratio, E/ Z
c
entry
silane
1
2
3
4
5d
6e
7e
8
9f
0g
(E)-1
(Z)-1
(E)-1
(Z)-1
(E)-1
(E)-1
(Z)-1
(E)-1
(E)-1
(E)-1
(Z)-1
(E)-1
(Z)-1
n-C5H11
H
n-C5H11
H
n-C5H11
n-C5H11
H
n-C5H11
n-C5H11
n-C5H11
H
H
C6H5
C6H5
1-naphthyl
1-naphthyl
1-naphthyl
10
10
30
30
30
180
180
10
60
180
10
(E)-3a
(Z)-3a
(E)-3b
(Z)-3b
(E)-3b
(E)-3c
(Z)-3c
(E)-3d
(E)-3d
(E)-3d
(Z)-3d
(E)-3e
(Z)-3e
91
90
89
85
76
83
81
93
87
74
92
95
94
97.8/2.2
2.7/97.3
96.5/3.5
3.3/96.7
96.6/3.4 (2.5% cine)
95.7/4.3
2.5/97.5
96.5/3.5
95.5/4.5
96.9/3.1
n-C5H11
H
n-C5H11
H
H
2-thienyl
2-thienyl
n-C5H11
H
H
H
n-C5H11
H
n-C5H11
4-(CH3CO)C6H4
4-(CH3CO)C6H4
4-(CH3CO)C6H4
4-(CH3CO)C6H4
4-(CH3O)C6H4
4-(CH3O)C6H4
1
1
1
1
1
2
3
4.8/95.2
97.2/2.8
2.6/97.4
n-C5H11
H
10
10
a
All reactions employed 1.1 equiv of 1 unless otherwise noted. b Yield of chromatographically homogeneous materials. c Determined by GC analysis.
d
.0 equiv of tetrabutylammonium hydroxide (2.0 M solution in CH3OH) was employed. e 1.2 equiv of 1 used. 1.0 equiv of TBAF was used. 1.2 equiv
f
g
2
of 1 and 2.5 mol % of [allylPdCl]2 were used with 4-bromoacetophenone; after 2 h, an additional equivalent of TBAF and 1.25 mol % of [allylPdCl]2 were
added.
5
.5% of the geometrical isomer was observed, starting from
The experiments described in Table 1 clearly demonstrate
that the influence of the different functional groups present
on the aryl iodide is minimal. The rate and yield of the
reactions are not affected, and the presence of electronically
neutral (entries 1-5), donating (entries 10 and 11), and
withdrawing (entries 8 and 9) substituents is well tolerated.
As was the case with alkenylsilacyclobutanes, silanols
(E)-1 and (Z)-1 undergo rapid and specific cross-coupling
with alkenyl iodides as well. For this study, geometrically
isomeric electrophiles (E)- and (Z)-6-iodo-5-hexenols were
employed (Table 3). Under conditions identical to those
employed previously, the vinyl iodides reacted with the
silanols to give conjugated dienes 4 in good yield. The
reactions were generally slower than the coupling reactions
with aryl iodides. In all cases, the desired products were
contaminated with a small and variable amount of isomeric
a single, pure isomer of the (E)- or (Z)-silanol.
Accordingly, the influence of the nontransferable group
on the rate and specificity of the coupling was studied by
submitting the diisopropylsilanols ((E)- and (Z)-2) to the
coupling reaction conditions. The results summarized in
Table 2 show clearly that the rates for the cross-coupling
are independent of the substituents on the silicon atom.
However, the selectivity of the reaction is now comparable
to the selectivity observed with silacyclobutane and sub-
stantially improved over the selectivity obtained with the
dimethylsilanols (for example, cf. Table 1, entries 1 and 2,
and Table 2, entries 1 and 2). Moreover, when tetrabutyl-
ammonium hydroxide was used as the activator (cf. Table
1, entry 5, and Table 2, entry 5), no cine rearrangement
product was observed.
Table 2. Palladium-Catalyzed Cross-Coupling of (E)-2 and (Z)-2 with Aryl Iodidesa
R1
R2
aryl
time, min
product
yield, %
b
ratio, E/ Z
c
entry
silane
1
2
3
4
5
6
7
(E)-2
(Z)-2
(E)-2
(Z)-2
(E)-2d
(E)-2
(Z)-2
n-C5H11
H
n-C5H11
H
n-C5H11
n-C5H11
H
H
C6H5
C6H5
1-naphthyl
1-naphthyl
1-naphthyl
10
10
30
30
30
10
10
(E)-3a
(Z)-3a
(E)-3b
(Z)-3b
(E)-3b
(E)-3d
(Z)-3d
82
81
85
79
78
80
86
99.2/0.8
0.6/99.4
98.4/1.6
2.3/97.7
99.2/0.8
>99.5/0.5
1.0/99.0
n-C5H11
H
n-C5H11
H
H
4-(CH3CO)C6H4
4-(CH3CO)C6H4
n-C5H11
a
All reactions employed 1.1 equiv of 2. b Yield of chromatographically homogeneous materials. c Determinded by GC analysis. d 2.0 equiv of
tetrabutylammonium hydroxide was used instead of TBAF.
Org. Lett., Vol. 2, No. 4, 2000
567

Table 3. Palladium-Catalyzed Cross-Coupling of (E)-1 and (Z)-1 Alkenyl Iodidesa
R1
R2
R3
R4
R5
time, min
product
yield, %
b
ratiosc,d
ratio 4/5
d
entry
silane
1
2
3
4
5e
6e
(E)-1
(E)-2
(Z)-1
(E)-1
(Z)-1
(Z)-2
n-C5H11
n-C5H11
H
n-C5H11
H
H
H
H
Me
i-Pr
Me
Me
Me
i-Pr
(CH2)4OH
(CH2)4OH
(CH2)4OH
H
H
H
H
H
H
90
90
90
90
300
300
(E,E)-4
(E,E)-4
(E,Z)-4
(Z,E)-4
(Z,Z)-4
(Z,Z)-4
91
87
72
73
64
68
95.8/4.2f
97.8/2.2
95.4/4.6g
5.9/94.1
12.2/87.8h
7.6/92.4h
86/14
96/4
91/9
>99/1
>99/1
93.2/6.8
n-C5H11
H
n-C5H11
n-C5H11
(CH2)4OH
(CH2)4OH
(CH2)4OH
a
b
c
All reactions employed 1.1 equiv of 1 and 5 mol % Pd(dba)2 unless otherwise noted. Yield of chromatographically pure materials. Isomeric purity
of major component. Determined by GC analysis. 1.5 equiv of 1 and 2.5 mol % of [allylPdCl]2 were used. Ratio (E,E)/(E,Z). g Ratio (Z,E)/(Z,Z)+(E,E).
Ratio (Z,Z)/all other isomers.
d
e
f
h
+
-
diene 5 which presumably arose from a cine rearrangement
pathway that was also observed previously. Stereospecificity,
again, is similar to that obtained with aryl iodides, and some
loss in configurational homogeneity of the double bond
arising from the silanol is observed, whereas the double bond
originating from the iodide is not affected. In entry 5, up to
transmetalation event.15 Both types of activators (R
4
N X
and Ag O) are in principle capable of acting as bases to
2
deprotonate the silanol and thus assist in the association with
the palladium intermediate. However, they differ in that both
fluoride and hydroxide can also act as nucleophiles and
further promote the transmetalation by forming siliconate
complexes. This is probably not possible with silver(I) oxide.
In summary, we have demonstrated that alkenylsilanols
can undergo highly stereospecific, palladium-catalyzed cross-
coupling reactions with either aryl or vinyl iodides under
extremely mild conditions. The reactions proceed cleanly and
in high yields with good functional group compatibility.
Current investigations focus on the scope of the silanol-based
cross-coupling as well as the mechanism of this unique
process.
10% of the stereoisomeric (E,Z)-4 was formed; although this
compound may be prone to isomerization, there is almost
twice as much isomerization as with silacyclobutane. In this
2
case a different palladium catalyst, [allylPdCl] , had to be
used, as Pd(dba) was not effective and led to even more
2
isomerization. When the methyl groups on the starting
silanols were replaced with isopropyl groups (entries 2 and
6), the selectivities were again improved to the ratios
observed with silacyclobutane.
The dramatic difference between the rate of coupling of
the alkenylsilanols in this report and those described recently
by Hiyama merits comment. Foremost among probable
explanations is the use of different palladium sources and
Acknowledgment. We are grateful to the National
Science Foundation for generous financial support (CHE
500397 and 9803124). D.W. thanks the Swiss National
Science Foundation for a postdoctoral fellowship.
9
3 4
activators. Hiyama employs Pd(PPh ) and silver(I) oxide
in DMF solution. In our hands, phosphine ligands inhibit
the process, but other additives can be helpful to keep the
palladium from precipitating in slow coupling reactions.
Furthermore, we have found that either tetrabutylammonium
fluoride or hydroxide is an effective promoter. Our working
hypothesis invokes an important association between the
silanol and the palladium center prior to and facilitating the
Supporting Information Available: Procedures for the
preparation and full characterization of (E)-1, (Z)-1, (E)-2,
and (Z)-2, spectroscopic data for 3a-3e and 4a-4c, and
representative procedures for coupling reactions. This mate-
rial is available free of charge via the Internet at http://
pubs.acs.org.
4
b,14
OL005565E
(14) Wang, Z., unpublished observations from these laboratories.
(15) Matos, K.; Soderquist, J. A. J. Org. Chem. 1998, 63, 461.
568
Org. Lett., Vol. 2, No. 4, 2000