Platinum oxide catalyzed silylation of aryl halides with triethylsilane: An efficient synthetic route to functionalized aryltriethylsilanes

Article abstract of DOI:10.1021/ol052996u

The first platinum-catalyzed selective silylation of aryl halides including aryl iodides and bromides having an electron-withdrawing group is described. The reaction takes place rapidly in NMP with triethylsilane as a silicon source and sodium acetate to provide functionalized aryltriethylsilanes in moderate to good yields. Heteroaromatic halides also were found to be readily silylated with triethylsilane. The procedure is chemoselective and tolerates a wide variety of functional groups.

Full text of DOI:10.1021/ol052996u

ORGANIC
LETTERS
2006
Vol. 8, No. 5
931-934
Platinum Oxide Catalyzed Silylation of
Aryl Halides with Triethylsilane: An
Efficient Synthetic Route to
Functionalized Aryltriethylsilanes
Abdallah Hamze, Olivier Provot, Mouaˆd Alami,* and Jean-Daniel Brion
Laboratoire de Chimie The´rapeutique, BioCIS - CNRS (UMR 8076),
UniVersite´ Paris-Sud XI, Faculte´ de Pharmacie, rue J.B. Cle´ment,
92296 Chaˆtenay-Malabry Cedex, France
mouad.alami@cep.u-psud.fr
Received December 12, 2005
ABSTRACT
The first platinum-catalyzed selective silylation of aryl halides including aryl iodides and bromides having an electron-withdrawing group is
described. The reaction takes place rapidly in NMP with triethylsilane as a silicon source and sodium acetate to provide functionalized
aryltriethylsilanes in moderate to good yields. Heteroaromatic halides also were found to be readily silylated with triethylsilane. The procedure
is chemoselective and tolerates a wide variety of functional groups.
Arylsilanes are valuable intermediates in organic synthesis,
and their use has been demonstrated in a number of reviews
which deal with Hiyama1 coupling and other related transi-
tion-metal-catalyzed coupling reactions.2
Accordingly, many synthetic efforts have been devoted
to their preparation. Classical synthetic routes to arylsilanes
consist of the reaction of aryl Grignard or aryllithium
compounds with silicon electrophiles.3 More recent strategies
involve the conversion of an sp2-carbon-halogen bond to
an sp2-carbon-silicon bond under transition-metal catalysts.
Typically, the palladium-catalyzed cross-coupling reaction
of aryl halides with disilanes as silicon sources has proven
to be a useful route to functionalized arylsilanes.4 Silylation5
with hydrosilanes has also been reported, indicating their
potential use as silylating reagents in the presence of
transition-metal complexes. Masuda6 and DeShong7 reported
the palladium-catalyzed silylation of aryl halides (I, Br) with
triethoxysilane.8 These reactions are effective with electron-
rich and -neutral para-substituted aryl halides. However, with
(3) (a) Lulinski, S.; Serwatowski, J. J. Org. Chem. 2003, 68, 9384-
9388. (b) Nishide, K.; Miyamoto, T.; Kumar, K.; Ohsugi, S. I.; Node, M.
Tetrahedron Lett. 2002, 43, 8569-8573. (c) Manoso, A. S.; Ahn, C.; Soheili,
A.; Handy, C. J.; Correira, R.; Seganish, W. M.; DeShong, P. J. Org. Chem.
2004, 69, 8305-8314. (d) Schlosser, M.; Heiss, C. Eur. J. Org. Chem.
2003, 4618-4624. (e) Oestreich, M.; Auer, G.; Keller, M. Eur. J. Org.
Chem. 2005, 184-195.
(4) (a) Denmark, S.; Kallemeyn, J. M. Org. Lett. 2003, 5, 3483-3486.
(b) Goo-en, L. K.; Ferwanah, A.-R. S. Synlett 2000, 1801-1803 and
references therein.
(1) For selected reviews on the Hiyama cross-coupling reaction, see: (a)
Hiyama, T. in Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; p 421. (b) Hiyama, T.;
Shirakawa, E. In Topics in Current Chemistry; Miyaura, N., Ed.; Springer-
Verlag: Heidelberg, 2002; Vol. 219, p 61. (c) Horn, K. A. Chem. ReV.
1995, 95, 1317-1350. (d) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845-
853. (e) Pierrat, P.; Gros, P.; Fort, Y. Org. Lett. 2005, 7, 697-700. (f) Ito,
H.; Sensui, H.; Arimoto, K.; Hosomi, A. Chem. Lett. 1997, 639-640. (g)
Fu, J. M.; Snieckus, V. Can. J. Chem. 2000, 78, 905-919. (h) Yoshikawa,
E.; Radhakrishnan, K. V.; Yamamoto, Y. Tetrahedron Lett. 2000, 41, 729-
731.
(5) For a recent review, see: Handy, C. J., Manoso, A. S.; McElroy, W.
T., Seganish, W. M., DeShong, P. Tetrahedron 2005, 61, 12201-12225.
(6) Murata, M.; Suzuki, K.; Watanabe, S.; Masuda, Y. J. Org. Chem.
1997, 62, 8569-8571.
(2) The Chemistry of Organic Silicon Compounds; Patai, S., Rappoport,
Z., Eds.; Wiley & Sons: New York, 2000.
(7) Manoso, A., S.; DeShong, P. J. Org. Chem. 2001, 66, 7449-7455.
10.1021/ol052996u CCC: $33.50
© 2006 American Chemical Society
Published on Web 02/08/2006

electron-deficient aryl halides the side reduction of the
carbon-halogen bond predominated. Murata9 reported that
a limited number of electron-deficient aryl bromides and
iodides also react with triethoxysilane in the presence of Rh(I)
catalyst. Quite recently, triethylsilane10 has been used as a
silylating reagent to achieve the silylation of aryl halides
under palladium catalysis,11 but again, this procedure is
restricted to electron-rich and -neutral para-substituted aryl
iodides.12 Yamanoi also mentioned that the presence of a
para electron-withdrawing group (e.g., -NO2) on the aromatic
ring interfered with the coupling reaction. Therefore, it would
be desirable to develop a new selective procedure that would
tolerate a wide range of functional groups to achieve the
direct trialkylsilyl transfer to electron-deficient aryl halides.
During the course of our study on the PtO2-catalyzed
hydrosilylation reaction of halogenated internal arylalkynes,13
we found that besides the H-Si bond addition, a side
halogen/silicon exchange-reaction occurred. A survey of the
literature revealed, to the best of our knowledge, that there
is no report of platinum-catalyzed silicon-aryl carbon bond
formation from aryl halides14 using hydrosilane derivatives.
Herein we report a useful and convenient synthetic route to
functionalized aryltriethylsilanes by PtO2-catalyzed silylation
of aryl halides including aryl iodides and bromides substi-
tuted with an electron-withdrawing group (Scheme 1).
Table 1. Optimization Reaction of Ethyl 4-Iodobenzoate 1a
with Triethysilane under Various Conditionsa
yieldb (%)
entry
base
i-Pr2NEt
Et3N
N-Me-piperidine NMP
Cs2CO3
AcOK
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
AcONa
solvent
[Pt]
PtO2
2a
3a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
NMP
NMP
54c
50
66
5d
67
90e
72
65
67
0
22
16
16
9
14
8
28
26
19
0
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
PtO2
NMP
NMP
NMP
DMA
DMF
DMPUf
CH2Cl2
dioxane PtO2
neat
NMP
NMP
NMP
NMP
0
0
7
PtO2
Pt(PPh3)4
Pt/C
PtCl2
H2PtCl6
12
20g
87h
30
17
29
13
70
83
a Reactions of ethyl 4-iodobenzoate 1a (1.0 mmol) with triethylsilane
(1.5 mmol) were performed at 70 °C for 1 h in 3 mL of solvent by using
PtO2 (5 mol %) and base (3 mmol). b Yields were determinated by GC
analysis. c No reaction occurred at room temperature. d 15% conversion were
observed by GC analysis after 1 h. e 2a was easily purified by flash
chromatography on silica gel; isolated yield of 2a 73%. f DMPU: 1,3-
dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. g 49% conversion were
observed by GC analysis after 1 h. h Isolated yield of 2a 70%.
Scheme 1
dinone) was first evaluated with i-Pr2NEt as a base. Thus,
at room temperature, no silylation occurred and starting
material 1a was recovered unchanged. However, at 70 °C
for 1 h, the reaction proceeded to give a mixture of the
silylated derivative 2a and the reduced byproduct 3a (entry
1, Table 1). It should be noted that this selectivity markedly
in favor of the desired product 2a was dependent on the
nature of the base (entries 2-6). Thus, in the presence of
tertiary amine, especially N-methylpiperidine, the formation
of 2a was improved (entry 3), whereas the use of mineral
base Cs2CO3 induced a lowering of the conversion rate and
the selectivity (entry 4). The use of sodium acetate was found
to be the most effective base for the selective formation of
arylsilane 2a (entry 6). Under these conditions, pure com-
pound 2a was obtained in a 73% isolated yield. It should be
noted that decreasing the amount of sodium acetate from
3.0 to 1.5 equiv had no effect on the yield and the selectivity
of the silylation (72% vs 73%). The influence of the solvent
was next investigated. Among several polar solvents tested
including DMA (N,N-dimethylacetamide), DMF, or DMPU
(entries 7-9), NMP is the unrivaled solvent choice for this
silylation. No reaction occurred in other solvents, such as
CH2Cl2 or dioxane (entries 10 and 11).
Initially, the silylation of ethyl 4-iodobenzoate 1a, as a
model substrate, was examined under various conditions.
This study showed that the selectivity of the reaction
(silylation vs reduction) depends greatly on the solvent, the
base, and the platinum catalyst. The results are summarized
in Table 1.
The reaction of 1a with triethylsilane (1.5 equiv) in the
presence of PtO2 (5 mol %) in NMP (N-methyl-2-pyrroli-
(8) Triethoxysilane is highly toxic, and contact with the eyes may cause
blindness; see: Encyclopedia of Reagents for Organic Synthesis; Paquette,
L. A., Ed.; Wiley: New York, 1995; Vol. 7, p 5083.
(9) Murata, M.; Ishikura, M.; Nagata, M.; Watanabe, S.; Masuda, Y.
Org. Lett. 2002, 4, 1843-1845.
(10) Triethylsilane generally works as a reducing reagent in the presence
of a palladium catalyst; see: Boukherroub, R.; Chatgilialoglu, C.; Manuel,
G. Organometallics 1996, 15, 1508-1510. See also ref 6.
(11) Yamanoi, Y. J. Org. Chem. 2005, 70, 9607-9609.
(12) For the coupling of butyldiethylsilane polystyrene with Boc-4-
iodophenylalanine methyl ester in the presence of palladium catalyst, see:
Gu, W.; Liu, S.; Silverman, R. B. Org. Lett. 2002, 4, 4171-4174.
(13) Hamze, A.; Provot, O.; Alami, M.; Brion, J.-D. Org. Lett. 2005, 7,
5625-5628.
(14) For the Pt-catalyzed coupling of silane Si-H bonds with aromatic
and aliphatic C-H bonds, see: (a) Tsukada, N.; Hartwig, J. F. J. Am. Chem.
Soc. 2005, 127, 5022-5023. For Ru-catalyzed silylation of aromatic C-H
bonds, see: (b) Kakiuchi, F.; Matsumoto, M.; Tsuchiya, K.; Igi, K.;
Hayamizu, T.; Chatani, N.; Murai, S. J. Organomet. Chem. 2003, 686, 134-
144.
In addition, the effect of platinum catalysts on the catalytic
activity was also evaluated. The use of Pt(PPh3)4 produced
an equal mixture of the arylsilane 2a and the reduced
derivative 3a (entry 13). In the presence of Pt/C, as catalyst,
however, the silylation reaction of 1a was effective, affording
a selectivity similar to that obtained with PtO2 catalyst
(compare entries 6 and 14), and 2a was obtained in a 70%
932
Org. Lett., Vol. 8, No. 5, 2006

isolated yield. When the reaction is carried out in the
presence of PtCl2 or H2PtCl6 as catalysts, the formation of
undesirable 3a predominated (entries 15 and 16). These
results clearly indicated that platinum catalysts with a
chlorine atom had a strong tendency to produce competitively
the reduced byproduct 3a. Accordingly, when exposing 1a
to Et3SiH (1.5 equiv) in NMP at 70 °C for 2 h in the presence
of BnNBu3Cl (1 equiv), Pt/C (5 mol %), and AcONa (3
equiv), the reduced byproduct 3a became dominant. The GC
analysis of the reaction mixture indicated the formation of a
mixture of 1a/2a/3a in a 30:30:40 ratio.
Table 2. PtO2-Catalyzed Silylation of Various Aryl Halides 1:
Synthesis of Functionalized Aryltriethylsilanes 2
Finally, the effect of other hydrosilanes under our opti-
mized conditions (PtO2, AcONa, NMP, 70 °C) was exam-
ined. The use of triethoxysilane induced a lowering of the
reactivity and prevented the formation of the siloxane
derivative.15 Other hydrosilanes16 including, PhMe2SiH, Me2-
EtOSiH, Ph2MeSiH, and i-Pr3SiH were also examined in this
reaction, but none of these reagents were more effective than
Et3SiH. Our study demonstrates that triethylsilane under PtO2
catalyst selectively acted as a silicon source for the coupling
of electron-deficient aryl iodide 1a. Moreover, since the
desired functionalized aryltriethylsilane 2a and the reduced
byproduct 3a were easily separated by flash chromatography
on silica gel, this new silylation complements the previous
procedure11 and provides a simple and widely available route
to functionalized aryl-triethylsilanes 2.
To demonstrate the scope of this new platinum-catalyzed
silylation reaction, a variety of representative aryl halides
was examined. Results summarized in Table 2 show that
the yield of the silylation reaction was affected by the
electronic and steric characteristics of the substrates used.
On the contrary, of the previous palladium-catalyzed sily-
lations,11 best yields of aryltriethylsilane 2 were obtained for
aryl halides with a π-electron-withdrawing group. As ex-
pected, the reactivity of aryl bromides was moderate in
comparison with aryl iodides (compare entries 1, 2 and 5,
6), but unfortunately, the corresponding electron-deficient
aryl chloride did not have enough reactivity, and as a
consequence, compound 1e was recovered unchanged (entry
4). Interestingly, the presence of a wide variety of electro-
philic functional groups (e.g., -CO2R, -CN, -NO2, -SO2-
NHR, -CHdNPh, -COR, -CHO, ...) on the aryl halides
1 did not interfere with the outcome of the present reaction
at 70 °C since the triethylsilane reactant was inert to many
functional groups (entries 1-17) even to the formyl func-
tionality17 (entry 15). The position of the substituent greatly
impacted the reaction outcome. Silylation of electron-
deficient para- and meta-substituted aryl halides gave in
moderate to good yields functionalized aryltriethylsilanes,
whereas the reaction with the ortho-substituted derivatives
a Reactions of aryl halide (1.0 mmol) with triethylsilane (1.5 mmol) were
performed at 70 °C in NMP (3 mL) in the presence of PtO2 (5 mol %) and
sodium acetate (3 mmol). b Isolated yield of silylated product after flash
chromatography on silica gel. c Yield was determinated by GC analysis.
d After purification, sensitive imine 2r was contaminated with a substantial
amount (22%) of aldehyde 2p. e Starting material was recovered unchanged.
(15) The GC analysis of the reaction mixture indicated the only formation
of the reduced product (15%) and starting halide (85%) after stirring for 1 h.
(16) Silylation yields of 1a with other hydrosilanes under the catalytic
conditions (PtO2 5 mol %, AcONa 3 equiv in NMP at 70 °C) are as
follows: PhMe2SiH 2x, 36%; Me2EtOSiH, traces; Ph2MeSiH, traces; i-Pr3-
SiH, traces.
(17) Exposing 4-iodobenzaldehyde 1p to Et3SiH at 70 °C for 2 h in the
absence of PtO2 catalyst gave 4-iodobenzyl alcohol (30%) and starting halide
(70%) after GC analysis of the reaction mixture.
gave poor yields of the silylated product due to a chelation
and/or a steric hindrance (entry 10).
Org. Lett., Vol. 8, No. 5, 2006
933

The reaction was also effective with neutral aryl iodides
and silylation of iodobenzene gave 70% of the corresponding
phenyltriethylsilane (entry 18). However, in contrast to
electron-deficient and -neutral para-substituted aryl iodides,
no silylation occurred with electron-rich para-substituted aryl
iodides and starting material was recovered unchanged (Table
2, entry 19). In the following examples, it is interesting to
note that heteroaromatic iodides and bromides were readily
silylated with triethylsilane without any difficulty. For
instance, 3-bromoquinoline (1u), 2-chloro-5-iodopyridine
(1v) and 3-iodopyridine (1w) afforded the corresponding
3-triethylsilanylquinoline (2u), 2-chloro-5-triethylsilanylpy-
ridine (2v), and 3-triethylsilanylpyridine (2w) in 50%, 67%,
and 48% yield, respectively (Table 2, entries 20-22).
Although there is no clear experimental evidence, we
suppose that the reaction proceeds as shown in Scheme 2.
intermediate B, in view of the high reactivity of Pt(II) toward
aryl halides demonstrated for some systems to give Pt(IV)
species.20 Accordingly, the formation of the intermediate B
via an oxidative addition process would be favorable in the
case of electron-deficient aryl halides and unfavorable with
electron-rich aryl halides. Reductive elimination of B in the
presence of AcONa would lead to a Pt(II) species C. A
subsequent reductive elimination21 of C produces the aryl-
silane product 2 and regenerates the platinum catalyst. The
reduced byproduct 3 would occur in the case that reductive
elimination of Et3SiX22 from B proceeded. However, at
present, we cannot rule out an alternative possibility that the
aryl halide and the Pt(II) species A evolve according to a
σ-bond metathesis between Si-Pt bond and C-X bond.
Species D1/D2 would produce the arylsilanes 2 and species
E1/E2 would give the reduced byproduct 3. However, since
there are many factors governing this elemental step, it is
not easy to conclude any clear rationale at this stage.
In conclusion, the present paper shows for the first time
that PtO2 proved to be a powerful and efficient catalyst for
the direct trialkylsilyl transfer to a variety of electron-
deficient and -neutral aryl halides using triethylsilane as
silylating reagents in the presence of AcONa. The procedure
is chemoselective and was also effective in the case of
heteroaromatic halides. This coupling reaction complements
the previous procedures11 and provides a new and efficient
synthetic route to a wide range of functionalized arytrieth-
ylsilanes. The investigations for silylation with other organic
halides or pseudo halides are currently in progress in our
laboratory.
Scheme 2
Acknowledgment. The CNRS is gratefully acknowledged
for financial support of this research.
Supporting Information Available: Experimental pro-
cedures and spectroscopic data of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
18
Initially, the PtO2 catalyst is probably reduced to metal
platinum and triethylsilane would add to the metal catalyst
to generate the H-PtII-SiEt3 complex A.19 Then a further
oxidative addition of Ar-X would form a platinum(IV)
OL052996U
(20) (a) Canty, A. J.; Patel, J.; Rodemann, T.; Ryan, J. H.; Skelton, B.
W.; White, A. H. Organometallics 2004, 23, 3466-3473. (b) Yahav, A.;
Goldberg, I.; Vigalok, A. Organometallics 2005, 24, 5654-5659. (c)
Anderson, C. M.; Puddephatt, R. J.; Fergusson, G.; Lough, A. J. J. Chem.
Soc., Chem. Commun. 1989, 1297-1298. (d) Canty, A. J.; Honeyman, R.
T.; Skelton, B. W.; White, A. H. J. Organomet. Chem. 1990, 389, 277-
288. (e) Canty, A. J.; Patel, J.; Skelton, B. W.; White, A. H. J. Organomet.
Chem. 2000, 599, 195-199.
(18) Similar results were obtained when the silylation of 1a was carried
out in the presence of PtO2 or Pt/C catalysts; compare entries 6 and 14 in
Table 1.
(19) For the formation of platinum metal silyl hydride complexes, see:
(a) Chan, D.; Duckett, S. B.; Heath, S. L.; Khazal, I. G.; Perutz, R. N.;
Sabo-Etienne, S.; Timmins, P. L. Organometallics 2004, 23, 5744-5756.
(b) Heyn, R. H.; Tilley, D. T. J. Am. Chem. Soc. 1992, 114, 1917-1919.
(c) Braddock-Wilking, J.; Levchinsky, Y.; Rath, N. P. Organometallics 2000,
19, 5500-5510.
(21) For the C(sp2)-Si reductive elimination from Pt(II) species, see:
Ozawa, F.; Tani, T.; Katayama, H. Organometallics 2005, 24, 2511-2515.
(22) Roy, A. K.; Taylor, R. B. J. Am. Chem. Soc. 2002, 124, 9510-
9524.
934
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