Fluoride-free cross-coupling of organosilanols

Full text of DOI:10.1021/ja016021q

J. Am. Chem. Soc. 2001, 123, 6439-6440
6439
Fluoride-Free Cross-Coupling of Organosilanols
Scott E. Denmark* and Ramzi F. Sweis
oxygen-palladium linkage (ii, Scheme 2) as a preassociation step
prior to transmetalation, thus rendering the rate-determining step
intramolecular.9 If the prerequisite for transmetalation is to
generate a pentacoordinate silicon, we hypothesized that a suitably
activated species (iii) might be accessible by attachment of a
second molecule of the silyloxide i with the arylpalladium
silyloxide ii as shown in Scheme 2. In this species the transferable
alkenyl group is on an “activated” silicon (central in iii) which
can then collapse to products though an accelerated transmetal-
Department of Chemistry, UniVersity of Illinois
00 South Mathews AVenue, Urbana, Illinois 61801
6
ReceiVed April 14, 2001
The palladium-catalyzed, cross-coupling reactions of organo-
silicon compounds to organic halides has, over the past decade,
emerged as a viable alternative to the well-established and
1
versatile Stille-Migita-Kosugi coupling of organostannanes and
10
ation step.
2
Suzuki-Miyaura coupling of organoboranes. Pioneering studies
3
by Kumada and Hiyama have shown that activation of organo-
Scheme 2
functional silicon compounds is possible by addition of a fluoride
source to promote the palladium-catalyzed, cross-coupling reac-
tions to various organic halides. Since this discovery, chloro- and
4
fluoroorganosilanes and orthosiliconates have been successfully
employed in cross-coupling reactions.
Recent disclosures from these laboratories (Scheme 1) have
5
a-c
demonstrated the synthetic potential of silacyclobutanes,
silanols,5 silyl hydrides, and cyclic silyl ethers for extremely
d,e
5e
5f
mild cross-coupling reactions which employ tetrabutylammonium
fluoride (TBAF‚3H O) as the activator.
2
Scheme 1
To test this hypothesis would simply involve the formation of
a soluble silyloxide salt in the presence of an appropriate
palladium catalyst. The results from our survey of bases and
solvents using (1-heptenyl)dimethylsilanol (E)-1 and 1-iodonaph-
thalene are collected in Table 1. Whereas the lithium silyloxide
was unreactive, the sodium salt, generated with NaH in THF
clearly manifested the feasibility of this new process (entries 1-4).
We found that 2.0 equiv of base was needed for complete
conversion, which was then used throughout.11 The reaction is
considerably faster in DMF and DME. Other sodium bases (i.e.,
NaOt-Bu) were less effective promoters. The use of potassium
hydride had a dramatic effect on the rate, giving complete con-
version within 15 min in DME. Finally, potassium tert-butoxide
was also able to promote the reaction and gave the highest yield
despite having the lowest rate of coupling. Weaker bases, such
Although significant progress has been made in advancing the
structural versatility of organosilicon cross-coupling, one serious
limitation is the use of a fluoride source as the promoter. The
need for this agent precludes employment of this reaction in, for
example, complex molecule synthesis where either of the coupling
substrates contains silyl protective groups. Moreover, TBAF is
not inexpensive and it also makes reaction workup cumbersome
on a large scale. Herein we report our successful efforts toward
the development of a non-fluoride-activated, organosilicon cross-
coupling using inexpensive commercially available reagents.7
Our discovery that all of the organofunctional silane precursors
converge to a common silanol intermediate in the presence of
6a
2
TBAF‚3H O illuminated the crucial role played by the hydroxyl
8
group on silicon. An intriguing proposal for the facility of this
silicon-based cross-coupling is the formation of a silicon-
2 3 3 4
as K CO and K PO , were ineffective. In all cases examined,
(
1) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b) Farina,
the reaction was shown to highly stereospecific.
Application of the optimal reaction conditions to the coupling
of (Z)-1 with 1-iodonaphthalene gave rapid cross-coupling but
V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1998, 50, 1. (c) Mitchell, T.
N. In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J.,
Eds.; Wiley-VCH: Weinheim, 1998; Chapter 4.
(
2) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (b) Suzuki, A.
In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, 1998; Chapter 2. (c) Suzuki, A. J. Organomet. Chem.
Table 1. Palladium-Catalyzed Coupling of (E)-1 with
-Iodonaphthalenea
1
1
999, 576, 147.
(
3) For a recent review of the field, see: Hiyama, T. In Metal-Catalyzed
Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998; Chapter 10.
(
4) (a) Tamao, K.; Kobayashi, K.; Ito, Y. Tetrahedron Lett. 1989, 30, 6051.
(
b) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684. (c) Mowery,
M. E.; DeShong, P. Org. Lett. 1999, 1, 2137. (d) Lee, H. M.; Nolan, S. P.
Org. Lett. 2000, 2, 2053.
entry
base
solvent
time, min
yield, %b
E/Z-2a
(
5) (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. (c) Denmark, S. E.; Wang,
Z. Synthesis 2000, 999. (d) Denmark, S. E.; Wehrli, D. Org. Lett. 2000, 2,
1
2
3
4
5
6
7
MeLi
NaH
NaH
NaH
KH
THF
THF
DMF
DME
THF
DME
DME
1440
480
90
-c,d
5
65. (e) Denmark, S. E.; Neuville, L. Org. Lett. 2000, 2, 3221. (f) Denmark,
85
99.7/0.3
99.5/0.5
99.5/0.5
99.7/0.3
99.6/0.4
99.4/0.6
S. E.; Pan, W. Org. Lett. 2001, 3, 61.
6) (a) Tetrabutylammonium fluoride trihydrate (Fluka): $624/mol. (b)
78
(
60
81
Potassium trimethylsilanolate (Aldrich): $63/mol.
120
15
180
85
(
2
7) Hiyama and Mori have reported the use of stoichiometric amounts of
KH
82
Ag
O as a coupling activator: (a) Hirabayashi, K.; Kawashima, J.; Nishihara,
KOt-Bu
90
Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1, 299. (b) Hirabayashi, K.; Mori,
A.; Kawashima, J.; Suguro, M.; Nishihara, Y.; Hiyama, T. J. Org. Chem.
a
All reactions performed with 2.0 equiv of base and 5 mol %
2
000, 65, 5342. Hiyama has also reported the use of 6 equiv of NaOH to
b
c
activate chlorosilanes in cross-coupling reactions: (c) Hagiwara, E.; Gouda,
Pd(dba)
2
.
Yields of chromatographically homogeneous material. 47%
d
K.; Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1997, 38, 439.
recovery of 1-iodonaphthalene. 40% yield of 1-methylnaphthalene.
1
0.1021/ja016021q CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/08/2001

6440 J. Am. Chem. Soc., Vol. 123, No. 26, 2001
Communications to the Editor
Table 3. Palladium-Catalyzed Coupling of (E)- and (Z)-1 with Aryl Iodidesa
entry
silane
R1
R2
aryl
time, h
product
yield, %
93c
ratio, E/Zb
1
2
3
4
5
6
7
8
9
1
1
1
1
1
(E)-1
(Z)-1
(E)-1
(Z)-1
(E)-1
(Z)-1
(E)-1
(Z)-1
(E)-1
(Z)-1
(E)-1
(Z)-1
(E)-1
(Z)-1
n-C
5
5
5
5
5
5
5
H
11
11
11
11
11
11
11
H
1-naphthyl
1-naphthyl
phenyl
2
9
0.5
7.5
9
13
1
9.5
0.25
0.25
0.25
0.25
9
(E)-2a
(Z)-2a
(E)-2b
(Z)-2b
(E)-2c
(Z)-2c
(E)-2d
(Z)-2d
(E)-2e
(Z)-2e
(E)-2f
(Z)-2f
(E)-2g
(Z)-2g
97.9/2.1
2.8/97.2
99.3/0.7
1.8/98.2
98.8/1.2
2.9/97.1
c
H
n-C
H
5
H
5
H
5
H
5
H
5
H
5
H
5
H
11
11
11
11
11
11
11
88
91
86
82
83
88
91
95
85
85
83
80
c
n-C
H
n-C
H
n-C
H
n-C
H
n-C
H
n-C
H
H
H
H
H
H
H
c
n-C
H
phenyl
c
4-(CH
4-(CH
4-(CH
4-(CH
3
3
3
3
CO)C
CO)C
6
H
H
4
c
n-C
H
6
4
c
d
O)C
O)C
6
H
H
4
99.3/0.7
1.1/98.9
c
e
n-C
H
6
4
f
4-(NO
4-(NO
2
)C
)C
6
H
H
4
98.5/1.5
3.8/96.2
99.8/0.2
0.7/99.3
99.5/0.5
f
0
1
2
3
4
n-C
H
2
6
4
f
4-(EtO
4-(EtO
2
C)C
C)C
2-(TBSOCH
2-(TBSOCH
6
H
4
f
n-C
H
2
6
H
4
f
2
)C
)C
6
6
H
H
4
f
g
n-C
2
4
14.5
76
2.0/98.0
a
Reactions employed 1.1 equiv of 1. Determined by GC analysis. c Yield of chromatographed, distilled products. Accompanied by 3.8%
b
d
e
f
g
cine-rearranged product. Accompanied by 6.2% cine-rearranged product. Yield of analytically pure material. at 50 °C.
in markedly lower yields, Table 2, entry 1. The remainder of the
mass balance was identified as naphthalene, presumably arising
from the formation of a palladium hydride species from the excess
KH. Although the formation of naphthalene could be suppressed
by the use of KOt-Bu, the reaction rate with this base was far
too low to be synthetically viable. Apparently, KOt-Bu is able to
compete with the silyloxide for the palladium center, thus serving
as a competitive inhibitor. From this observation, we reasoned
that the ideal base need only be strong enough to produce a meas-
urable equilibrium concentration of the silyloxide, be capable of
associating with and activating species such as ii, and not be a
in DME at room temperature. The results in Table 3 illustrate
that cross-coupling products were obtained in excellent yields with
reasonable rates. High stereospecificities and good yields were
obtained in the coupling of (E)- and (Z)-1 to 1-iodonaphthalene
and iodobenzene. In addition, both electron-rich (entries 7 and
8) and electron-deficient (entries 5-6 and 9-12) arenes couple
quite well, although with varying rates. In general, electron-
deficient electrophiles couple most rapidly, except 4-iodo-
acetophenone. Apparently, the presence of a moderately acidic
proton in the substrate has a detrimental effect on the rate of cou-
pling, although the yields were still high and no other byproducts
were observed. In contrast to the fluoride-activated couplings of
silanols, the rates of coupling with (Z)-1 were significantly lower
than those with (E)-1. The synthetic potential of this new method
was clearly demonstrated by the compatibility of a silyl protective
group as shown in entries 13-14. The coupling reaction occurs
cleanly in the presence of a TBS-protected alcohol on the aryl
iodide, 9g, without any obserVable deprotection.14
competitive inhibitor. Logically, the first choice would be another
silyloxide such as the inexpensive6b and soluble agent KOSiMe
12
3
.
We were delighted to find that 2.0 equiv of this mild base could
effect the cross-coupling at room temperature, in excellent yield,
with stereospecificity and without reduction byproducts (albeit
more slowly than KH).13 Neither increasing nor decreasing the
amount of KOSiMe
3
improved the rate of the coupling.
In conclusion, we have developed a synthetically useful non-
fluoride-activated, silicon-based, cross-coupling reaction that
employs inexpensive, commercially available reagents. The
success of in situ generated silyloxide also demonstrates the
mechanistically fascinating duality of the silanol moiety as a
prosthetic group for controlled carbon-carbon bond formation
and as an activator for the coupling. Current efforts to expand
the scope of coupling partners with this method as well as to
elucidate the kinetic behavior and detailed mechanism of the
reaction are in progress.
Table 2. Palladium-Catalyzed Coupling of (Z)-1 with
a
1
-Iodonaphthalene
entry
base
KH
KOt-Bu
KOSiMe
KOSiMe
KOSiMe
KOSiMe
equiv
time, h
yield, %
Z/E-2a
b
1
2
3
4
5
6
2.0
2.0
2.0
3.0
1.0
0.25
24
8
8
18
8
48
98.3/1.7
85.5/14.5
98.0/2.0
-
-
-
Acknowledgment. We are grateful to the National Science Foundation
for generous financial support (NSF CHE 9803124). We also thank Dr.
Daniel Wehrli for important preliminary experiments and discussions.
R.F.S. thanks R. W. Johnson for a graduate fellowship.
c
53
3
3
3
3
88
d
73
d
74
e
d
Supporting Information Available: Representative procedures for
the coupling reactions (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
2.0
85
a
. b 30% of naphthalene
All reactions employed 5 mol % Pd(dba)
2
c
d
isolated. 65% conversion of 1-iodonaphthalene. Conversion, %.
.25 equiv of (Me Si) O added.
3 2
e
JA016021Q
0
(
11) We surmise that the need for 2.0 equiv of base is due to the competitive
1
formation of symmetrical disiloxane (observed by H NMR) with lesser
amounts of base.
The scope of this new, fluoride-free coupling process was
examined under the optimal conditions of 2.0 equiv of KOSiMe
3
(12) Potassium trimethylsilanolate has found use for dealkylative cleavage
of esters, and hydrolysis of nitriles. (a) Laganis, E. D.; Chenard, B. L.
Tetrahedron Lett. 1984, 25, 5831. (b) Merchant, K. J. Tetrahedron Lett. 2000,
41, 3747.
(
8) (a) Denmark, S. E.; Wehrli, D.; Choi, J. Y. Org. Lett. 2000, 2, 2491.
(
b) Wehrli, D. Unpublished studies in these laboratories.
(9) Such an interaction has been proposed for the Suzuki coupling
(13) We were concerned that the in situ formation of (Me
some way influence the reaction. Thus, we added this reagent to the reaction
with KOSiMe (Table 2 entry 6) and observed only negligible effects.
(14) The compatibility of a TES group to KOSiMe (10 equiv) has been
3 2
Si) O might in
recently: (a) Matos, K.; Soderquist, J. A. J. Org. Chem. 1998, 63, 461. (b)
Ridgway, B. H.; Woerpel, K. A. J. Org. Chem. 1998, 63, 458.
3
(
10) For a discussion of the how oxygen substituents on palladium
3
accelerate transmetalation, see: Miyaura. N.; Yamada, K.; Suginome, H.;
documented as well. Barrett, A. G. M.; Pe n˜ a, M.; Willardsen, J. A. J. Org.
Chem. 1996, 61, 1082.
Suzuki, A. J. Am. Chem. Soc. 1985, 107, 972.