Palladium-catalyzed direct arylation of cyclic enamides with aryl silanes by sp2 C-H activation

Full text of DOI:10.1002/anie.200901884

Angewandte
Chemie
DOI: 10.1002/anie.200901884
À
C H Activation
Palladium-Catalyzed Direct Arylation of Cyclic Enamides with Aryl
2
À
Silanes by sp C H Activation**
Hai Zhou, Yun-He Xu, Wan-Jun Chung, and Teck-Peng Loh*
The Hiyama coupling reaction, which involves the palladium-
catalyzed coupling between organohalides or other surrogates
Table 1: Screening conditions for the palladium(II)-catalyzed direct
arylation of 1a with phenyltrimethoxysilane.[a]
À
with organosilanes, is one of the most useful tools for C C
bond formation.[1] Compared with similar coupling reactions
using organostannane, Grignard, and organoboron reagents,
Hiyama coupling has many advantages, such as environ-
mental benignity, atomic efficiency, and safe handling.
Entry
[Pd]
Fluoride
Solvent
Yield [%][b]
À
À
Recently, new C C bond forming methods involving C H
activation have attracted much interest among chemists.[2]
Although many groups have reported direct arylation with
organoboronic acids,[3,2g] there is still very few studies on the
1
2
3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
[Pd(PPh3)2Cl2]
[Pd(OTFA)2][d]
[Pd(PhCN)2Cl2]
PdCl2
CuF2
TBAF[d]
CsF
dioxane
dioxane
dioxane
dioxane
dioxane
DCE
12
0
0
4
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
AgF
73
61
30
25
44
37
32
47
51
18
5[c]
6
À
direct coupling using organosilanes by C H functionaliza-
tion.[2i] Herein, we present the first direct cross-coupling
reaction between an enamide and organosilanes via vinylic
7
8
9
10
11
12
13
toluene
DMF
À
C H bond activation using a palladium catalyst.
CH3CN
dioxane
dioxane
dioxane
dioxane
Recently, our group has successfully developed a direct
cross-coupling reaction between cyclic enamides and arylbor-
onic acid[4a] or acrylate[4b] involving C H bond activation. We
À
envisioned the same substrate could also be used in the direct
arylation with organosilane reagents. We began our inves-
tigation by studying the Hiyama-type coupling reaction of 4-
chromanone-derived enamide 1a with trimethoxyphenylsi-
lane 2a in the presence of Pd(OAc)2 as a catalyst under
various reaction conditions (Table 1).[5] In our initial screen-
ing of fluoride sources, it was gratifying to find that AgF could
afford the desired product in high yield (Table 1, entry 4). We
hypothesized that AgF not only plays a role as a simple
fluoride to activate the organosilane, but also as an oxidant to
reoxidize Pd0 to PdII and thus fulfill the catalytic cycle. Three
equivalents each of both AgF and PhSi(OMe)3 was found
necessary for complete consumption of the substrates
(Table 1, entries 4 versus 5). Other additional inorganic
oxidants, such as Cu(OAc)2, were screened with this coupling
reaction, but afforded the desired product in low yields.
Among the different solvents screened, dioxane is the most
suitable for this transformation (Table 1, entries 4, 6–9).
Various palladium species were also examined, but the
[a] Conditions: 10 mol% Pd(OAc)2, 3 equiv of 2a, 3 equiv of fluoride,
808C, 16 h. [b] Yields of isolated products. [c] Conditions: 10 mol%
Pd(OAc)2, 2 equiv of 2a, 2 equiv of fluoride, 808C, 16 h. [d] OTFA=
trifluoroacetate, TBAF=tetra-n-butylammonium fluoride.
transformation works well only in the presence of Pd(OAc)2
as a catalyst (Table 1, entries 4, 10–13).
The direct arylation of 4-chromanone-derived enamide 1a
with various trialkoxy aryl silanes was surveyed with
10 mol% Pd(OAc)2 and 3 equiv AgF in dioxane (Table 2).
Triethoxyphenylsilane was a little less reactive than trime-
thoxyphenylsilane (Table 2, entries 1 versus 2). The arylated
products were obtained in moderate to high yields by the
coupling with different triethoxy aryl silanes having electron-
donating or electron-withdrawing groups on the phenyl ring.
The position of these substituents has a great influence on this
transformation. Meta and para substituents introduced on the
phenyl ring of phenylsilane could afford the coupling
products in good yields. However, ortho-substituted phenyl-
silanes give very little of the desired products, which perhaps
arises from steric effects. It is noteworthy that a chloro
substituent on the trialkoxy phenylsilane shows tolerance
toward this coupling reaction, which could serve as a handle
for further transformation (Table 2, entry 5).
[*] H. Zhou, Y. H. Xu, W. J. Chung, Prof. T. P. Loh
Division of Chemistry and Biological Chemistry,
School of Physical and Mathematical Sciences,
Nanyang Technological University,
Singapore 637371 (Singapore)
Fax: (+65)6515-8229
To examine the scope of this direct arylation, various
cyclic enamides were subjected to the reaction conditions
(Table 3). Both electron-donating and electron-withdrawing
groups on the phenyl ring of 4-chromanone-derived enamides
1 afforded the coupling products in moderate to excellent
yields (Table 3, entries 1–4). Of note, a chloro group on the
phenyl ring of enamide, which tolerated the reaction con-
E-mail: teckpeng@ntu.edu.sg
[**] We gratefully acknowledge the Nanyang Technological University
and the Singapore Ministry of Education Academic Research Fund
Tier 2 (T206B1221; T207B1220RS) for the financial support of this
research.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200901884.
Angew. Chem. Int. Ed. 2009, 48, 5355 –5357
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Table 2: Palladium-catalyzed direct arylation of 1a with silyl reagents 2.[a]
Table 3: Palladium-catalyzed direct arylation of various cyclic enamides 1
with phenyltrimethoxysilane 2a.[a]
Entry
2
3
Yield
[%][b]
Entry
1
1
3
Yield [%][b]
73
1
2
2a
2b
3aa
3aa
73
66
1a
1b
1c
1d
1e
1 f
3aa
3ba
3ca
3da
3ea
3 fa
2
72
47
95
43
19
3
4
5
6
7
8
2c
2d
2e
2 f
3ac
3ad
3ae
3af
51
54
55
56
50
40
3
4
5[c]
6
7[d]
1g
1h
3ga
3ha
81
43
2g
2h
3ag
3ah
8[d]
[a] Conditions: 10 mol% Pd(OAc)2, 3 equiv of 2a, 3 equiv of fluoride,
808C, 16 h. [b] Yields of isolated products. [c] 55% of the starting
material was recovered. [d] Some aromatized byproduct of the starting
material was observed in the reaction.
[a] Conditions: 10 mol% Pd(OAc)2, 3 equiv of 2, 3 equiv of fluoride,
808C, 16 h. [b] Yields of isolated products.
cycle 4 to give palladium species 5, which, upon reductive
elimination, produced the cross-coupling product and palla-
ditions, could also be used for further transformation (Table 3,
entry 4). Substitution on the alicyclic ring of enamides could
also be applied to give the coupling products, but in relatively
low yields. In particular, for the substrate disubstituted on the
alicyclic ring, the yield was only 19% (Table 3, entry 6). This
may well result from large steric hindrance to the adjacent
À
vinylic C H position of the enamide. Furthermore, applica-
tion of this transformation to a-tetralone-derived enamides
also produced the desired product in high yields (Table 3,
entries 7 and 8).
Although there is the possibility of a Heck-type reaction
pathway for this coupling reaction, we believe that the
reaction may go through palladation of cyclic enamides,
which is similar to the mechanism of direct arylation of
enaminones[2m] and to that of aromatic C H activation
À
reported by the groups of Inuoe[6] and Shi[2i] (Scheme 1).
Assisted by the acetamino group, six-membered palladacycle
4 is first formed. Next, with activation by fluoride, the aryl
group from trialkoxy silane 2 is transmetalated with pallada-
Scheme 1. Proposed mechanism of the direct arylation of cyclic
enamides.
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dium(0). The elemental palladium is then reoxidized to PdII
by AgI to fulfill the catalytic cycle.
In conclusion, we have developed a palladium-catalyzed
direct cross-coupling method for arylation of cyclic enamides
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À
with trialkoxy aryl silanes by a C H activation to produce a
wide variety of enamide derivatives.[7] Future studies will
focus on its potential application and on understanding of the
mechanism of this transformation.
Experimental Section
General procedure for cross-coupling of cyclic enamides with
trialkoxy aryl silanes: Cyclic enamide 1 (0.27 mmol), Pd(OAc)2
(6.7 mg, 0.03 mmol, 10 mol%), trialkoxy aryl silane 2 (0.81 mmol,
3 equiv) and anhydrous 1,4-dioxane (4 mL) were added to a 8 mL
vial. AgF (102 mg, 0.81 mmol, 3 equiv) was slowly added to the
mixture, and the vial was then capped tightly and stirred for 10 min at
room temperature. The reaction was heated for 16 h at 808C in an oil
bath and the progress of the reaction monitored by thin-layer
chromatography. After removal of the solvent, the residue was
purified by flash chromatography to give pure products 3.
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Received: April 8, 2009
Published online: June 16, 2009
À
À
Keywords: arylation · C C coupling · C H activation ·
enamides · palladium
.
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