Silanol as a removable directing group for the pdII-catalyzed direct olefination of arenes

Article abstract of DOI:10.1002/chem.201103171

Need some direction? Silanol was developed as a directing group for the Pd^II-catalyzed oxidative Heck-type reaction of arenes. A one-pot C-H activation/desilylation process of benzyldiisopropylsilanol was also demonstrated, providing a powerful approach for the synthesis of ortho-alkenyl-substituted alkylarenes (see scheme). Considering the easily attachable and readily removable properties of the silanol group, this reaction will find broad synthetic applications.

Full text of DOI:10.1002/chem.201103171

COMMUNICATION
DOI: 10.1002/chem.201103171
Silanol as a Removable Directing Group for the PdII-Catalyzed Direct
Olefination of Arenes
Cong Wang and Haibo Ge*[a]
Aryl alkenes are important structural units in natural
products, organic materials, and medicinal compounds,
therefore a variety of synthetic methods have been devel-
oped to introduce this group.[1] Among them, the palladium-
catalyzed Mizoroki-Heck reaction of aryl halides is a fre-
quently used approach due to its high regio- and stereoselec-
tivity, high functional group tolerance, and mild reaction
conditions.[2] In many cases, the prerequisite regioselective
introduction of a halide onto an arene requires several syn-
thetic steps, which reduces the overall efficiency of this
method.
Scheme 1. Synthesis of benzyldiisopropylsilanols (2).
ogen-containing solvents are the best for this reaction, with
optimal results obtained with CHCl3 (Table 1, entry 1). Fur-
ther investigation showed that a PdII source is required for
this reaction (Table 1, entry 5), whereas the use of Li2CO3 is
optional (Table 1, entry 6). Thus, other sources of palladium
were examined, and it was found that this reaction could
The oxidative Heck-type reaction of arenes through PdII-
À
catalyzed C H functionalization offers an attractive alterna-
tive since this method does not require the prefunctionaliza-
tion of arenes.[3] Such reactions often rely on the use of di-
also be catalyzed by 10 mol% of [PdACTHNURGTNEUNG(MeCN)2Cl2] or
recting groups, which coordinate a metal and subsequently
20 mol% of [(h3-C3H5)2Pd2Cl2], albeit with a lower yield
[4]
À
direct the metalation of a specific C H bond. Often, the
(Table 1, entries 7 and 8). It is noteworthy that increasing
the amount of [PdACHTGUNTERNNU(G MeCN)2Cl2] to 20 mol% did not improve
installation and removal of common directing groups re-
quires multiple steps and/or harsh reaction conditions, which
limits the potential application of this transformation.
Therefore, the need for novel, readily accessible substrates
containing easily attachable and removable directing groups
is clear. In such cases, the reactions will be directed by these
groups to ensure the regioselectivity, and the initial products
will, following removal of the directing group, be trans-
formed into synthetically useful products.[5] In pursuit of this
objective, we directed our attention to silanol-based arenes
because of their ready accessibility (Scheme 1)[6] and the
easy removability of the silanol group.[7] Herein, we report
the PdII-catalyzed silanol-directed oxidative Heck-type reac-
tion of benzyldiisopropylsilanols (2a).[8]
the reaction yield. Interestingly, the addition of a stoichio-
metric or catalytic amount of acid such as KH2PO4, AcOH,
EtCO2H, H3PO4, or HO2CCO2H improved the reaction
yield, with optimal results obtained with KH2PO4 (Table 1,
entries 11–15). Further investigation of the reaction condi-
tions showed that the choice of an oxidant is crucial in this
reaction (Table 1, entries 16 and 17). Furthermore, the yield
slightly decreased with a lower concentration of alkene 3a
(Table 1, entry 18), or when the reaction was performed at
an elevated reaction temperature (Table 1, entry 19). In ad-
dition, it was observed that reducing the amount of [Pd-
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
Inspired by the recent reports of the PdII-catalyzed hy-
A
ACHTUNGTRENNUNG
[4n,9]
À
droxyl-directed C H activation from the Yu group,
we
to produce the corresponding desired product in a moderate
yield, decomposition of this substrate occurred using the
current catalytic system.
began our investigation on direct olefination of benzyldiiso-
propylsilanol (2a) with ethyl acrylate (3a) in the presence
of [Pd
(OAc)2] (20 mol%), AgOAc (2 equiv), and Li2CO3
The compatibility of alkenes 3 is summarized in Table 2.
All terminal acrylates gave the corresponding products in
good yields (4a–f, 72–83%), whereas N,N-dimethylacryl-
amide provided a moderate yield of the product (4g, 56%).
Furthermore, a,b-unsaturated ketones, sulfonates, and ni-
triles were also effective substrates (4h–j, 50–60%). In com-
parison, the more electron-rich olefin such as styrene and 2-
vinylnaphthalene gave poor or no yield of the product (4k
(2 equiv; Table 1). Solvent screening demonstrated that hal-
[a] Dr. C. Wang, Prof. Dr. H. Ge
Department of Chemistry and Chemical Biology
Indiana University Purdue University Indianapolis
402 N. Blackford St. Indianapolis, IN 46202 (USA)
Fax : (+1)317-274-4701
and 4l) due to their low reactivity, which is an often encoun-
E-mail: geh@iupui.edu
II
À
tered limitation in the Pd -catalyzed C H activation of
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201103171.
arenes.[10]
Chem. Eur. J. 2011, 17, 14371 – 14374
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
14371

Table 1. Optimization of reaction conditions.[a]
À
quential one-pot, two-step C
functionalization followed
H
by desilylation, could be car-
ried out to provide the desired
product
5 in a good yield,
making this transformation a
powerful approach for the syn-
thesis of ortho-alkenyl-substi-
tuted alkylarenes, which are
not easily or efficiently ach-
ieved by current methods
(Scheme 2, reaction 2).[2c] It is
Entry
N
Oxidant
[2 equiv]
Additive
ACHTUNGTRNE(NUNG equiv)
Solvent
Yield
[%][b]
R
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18[d]
19[e]
20
N
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
Ag2CO3
Li2CO3 (2)
Li2CO3 (2)
Li2CO3 (2)
Li2CO3 (2)
Li2CO3 (2)
–
Li2CO3 (2)
Li2CO3 (2)
KHCO3 (2)
NaOAc (2)
KH2PO4 (2)
HOAc (0.1)
EtCO2H (0.1)
H3PO4 (0.1)
HO2CCO2H (0.05)
KH2PO4 (2)
KH2PO4 (2)
KH2PO4 (2)
KH2PO4 (2)
KH2PO4 (2)
CHCl3
CH2Cl2
CH2Br2
DCE
63
45
41
32
0
51
54
40
E
N
R
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
N
noteworthy that
a
one-pot
G
PdII-catalyzed direct olefina-
tion of N,N-dimethylbenzyl-
AHCTUNGTERGaNNUN mines followed by removal of
the group under reductive con-
ditions was achieved recently
by Shi and co-workers, to se-
R
55
48
R
C
76 (73)[c]
66
ACHTUNGTRENNUNG
G
60
62
65
35
23
66
62
44
N
lectively
functionalize
the
E
N
ortho-position of toluene deriv-
atives.[11] However, alkenes and
halogens were not compatible
under conditions used for re-
moval of the N,N-dimethyl-
G
CuN
G
AgOAc
AgOAc
AgOAc
T
A
[a] Conditions: 2a (0.3 mmol), 3a (0.6 mmol), [PdX2], oxidant, solvent (3.0 mL), 1008C, 16 h unless otherwise
noted. [b] Yields determined by crude 1H NMR spectroscopy using an internal standard based on 2a. [c] Iso-
lated product yield based on 2a. [d] 3a (0.45 mmol). [e] 1208C.
AHCTUNGTERGaNNUN mino group, thus restricting
the product diversity.
According to our proposed
reaction pathway, this process
is initiated by the regioselec-
The compatibility of benzyldiisopropylsilanols (2) is sur-
veyed in Table 3. Both electron-donating and electron-with-
drawing groups were successful with our catalytic system,
with the former generally providing higher yields. In addi-
tion, halogens such as Cl and F were tolerated under these
reaction conditions (4n, 4q, and 4r). Furthermore, diiso-
propyl(1-phenylethyl)silanol and diisopropyl(naphthalen-2-
ylmethyl)silanol also provided good yields of the products
(4x and 4y).
The removability of the silanol directing group was con-
firmed by the treatment of 4a with tetrabutylammonium
fluoride (TBAF) at room temperature to provide a high
yield of product 5 (Scheme 3, reaction 1). In addition, a se-
tive cyclopalladation of benzyldiisopropylsilanols (2) with a
PdII source, directed by the silanol group (Scheme 3). Coor-
dination of the resulting PdII–Ar species I with an olefin 3,
followed by 1,2-migratory insertion and subsequent b-hy-
dride elimination, provides the desired product 4. Pd0 gener-
ated in situ is re-oxidized to PdII by the AgI species.
In summary, silanol was demonstrated as an effective di-
recting group for the direct olefination of arenes through
À
palladium-catalyzed C H activation. In addition, the remov-
Scheme 2. Desilylation of ortho-olefinated benzyldiisopropylsilanol (4a),
À
and a one-pot C H activation/desilylation.
Scheme 3. Plausible catalytic cycle.
14372
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Chem. Eur. J. 2011, 17, 14371 – 14374

Silanol as a Removable Directing Group
COMMUNICATION
Table 2. Scope of olefins (3).[a,b]
Table 3. Scope of benzyldiisopropylsilanols (2).[a,b]
Product
Yield
[%]
Product
Yield
[%]
Product
Yield Product
[%]
Yield
[%]
4a
4b
4c
4d
4e
4 f
73
76
81
72
73
83
4g
4h
4i
56
56
60
50
36
0
4m 71
4t 68
4n 49
4u 68
4o 91
4v 59
4j
4k
4l
4p 88
4w 62
4q 71
4r 70
4s 36
4x 85
4y 79
[a] Conditions: 2a (0.3 mmol),
3 (0.6 mmol, 2 equiv), [PdACHTUNTGERNUN(G OAc)2]
(0.06 mmol, 20 mol%), AgOAc (0.6 mmol, 2 equiv), KH2PO4 (0.6 mmol,
2 equiv), CHCl3 (3.0 mL), 1008C, 16 h. [b] Isolated product yields based
on 2a.
ability of the silanol group on the product 4a was confirmed
À
under mild conditions. Furthermore, a one-pot C H activa-
tion/desilylation process of benzyldiisopropylsilanol was also
developed. The reaction sequence provides a novel and at-
tractive approach for the synthesis of ortho-alkenyl-substi-
tuted alkylarenes.
[a] Conditions:
2 (0.3 mmol), 3a (0.6 mmol, 2 equiv), [PdACHTUNGTRENNUNG(OAc)2]
(0.06 mmol, 20 mol%), AgOAc (0.6 mmol, 2 equiv), KH2PO4 (0.6 mmol,
2 equiv), CHCl3 (3.0 mL), 1008C, 16 h. [b] Isolated product yields based
on 2.
Acknowledgements
We gratefully acknowledge Indiana University Purdue University Indian-
apolis for financial support. The Bruker 500 MHz NMR spectrometer
was purchased using funds from a NSF-MRI award (CHE-0619254).
Experimental Section
General procedure for direct olefination of benzyldiisopropylsilanols: A
20 mL oven-dried pressure tube was charged with benzyldiisopropylsila-
nol (2, 0.3 mmol), olefin (3, 0.6 mmol), KH2PO4 (0.6 mmol), [PdACTHNUTRGNEUNG(OAc)2]
(0.06 mmol), AgOAc (0.6 mmol), and CHCl3. The reaction tube was then
sealed, heated to 1008C, and stirred for the noted time. The reaction mix-
ture was cooled to room temperature, diluted with EtOAc, filtered
through a pad of Celite, and the filtrate was then removed under vacuo.
The crude product was purified by flash chromatography on silica gel
(gradient eluent of EtOAc in hexane: 0 to ca. 10%, v/v) to yield the
product 4.
Keywords: arenes
palladium · silanols
·
directing groups
·
olefination
·
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Received: October 7, 2011
Published online: November 17, 2011
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Chem. Eur. J. 2011, 17, 14371 – 14374