Platinum(II)-catalyzed intermolecular hydroarylation of unactivated alkenes with indoles

Article abstract of DOI:10.1039/b607286k

Ethylene, α-olefins, and vinyl arenes undergo platinum-catalyzed hydroarylation with substituted indoles in moderate to good yield. The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b607286k

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Platinum(II)-catalyzed intermolecular hydroarylation of unactivated
alkenes with indoles{
Zhibin Zhang, Xiang Wang and Ross A. Widenhoefer*
Received (in Berkeley, CA, USA) 22nd May 2006, Accepted 29th June 2006
First published as an Advance Article on the web 31st July 2006
DOI: 10.1039/b607286k
conversion of 1 to 3 was such that 0.05 mol% of 2 was sufficient to
achieve 90% isolated yield of 3 (TON = 900; Table 1, entry 1). The
Pt-catalyzed hydroarylation of ethylene tolerated the presence of
either an electron-donating or electron-withdrawing group at the
C(5) position of the indole moiety or a phenyl group at the C(2)
position of the indole moiety (Table 1, entries 2–5). Substitution at
the C(2) position of the indole appeared to facilitate intermolecular
hydroarylation, but was not required (Table 1, entry 6).
Ethylene, a-olefins, and vinyl arenes undergo platinum-
catalyzed hydroarylation with substituted indoles in moderate
to good yield.
The intermolecular hydroarylation of unactivated alkenes has
attracted considerable attention as an atom-economical approach
to the functionalization of arenes. However, despite prolonged
effort in this area, general and effective methods for the selective
intermolecular hydroarylation of unactivated alkenes remain
scarce.1 Strong Lewis acids such as AlCl3 catalyze the hydroaryla-
tion of unactivated alkenes, but these approaches suffer from poor
selectivity and limited functional group compatibility.2 Ru(II)-3
and Rh(I)-4 phosphine complexes catalyze the intermolecular
hydroarylation of unactivated alkenes with arenes that possess a
suitable directing group or that are predisposed to the formation of
a stabilized carbene intermediate, respectively. Ir(III),5 cationic
Pt(II),6 and Ru(II) hydridotris(pyrazolyl)borate complexes7 cata-
lyze the hydroarylation of unactivated alkenes with benzene, but
require forcing reaction conditions (¢180 uC) or a large excess of
benzene. Brønsted acids catalyze the addition of aniline to
norbornene and vinyl arenes to form mixtures of hydroarylation
and hydroamination products.8 The cationic zirconocene complex
Cp2Zr(CH3)(THF)+ catalyzes the hydroarylation of propene with
a-picoline but is restricted to this lone example.9
ð1Þ
a-Olefins also underwent Pt-catalyzed hydroarylation with
indoles with predominant formation of the Markovnikov addition
product. For example, reaction of 1 with propene (50 psi) and a
catalytic amount of PtCl2 (5 mol%) in dioxane that contained a
trace (5 mol%) of HCl at 90 uC for 14 h led to isolation of a 6 : 1
mixture of 3-isopropyl-1,2-dimethylindole (4a) and 3-n-propyl-1,2-
dimethylindole (4b) in 88% combined yield (Table 2, entry 1).§
Likewise, Pt-catalyzed reaction of 1 with 1-butene (30 psi) led to
isolation of a 6 : 1 mixture of 5a and 5b in 74% combined yield
(Table 2, entry 2). Vinyl arenes also underwent Pt-catalyzed
hydroarylation with indoles. In an initial experiment, reaction of 1
and p-chlorostyrene with a catalytic amount of PtCl2 (5 mol %)
in dioxane at 120 uC for 16 h led to .95% conversion to form a
6.5 : 10.3 : 1.0 mixture of Markovnikov adduct 6a, anti-
Markovnikov adduct 6b, and oxidized Markovnikov product 6c
in 89% combined yield (GC, Scheme 1). Unfortunately, neither
unreacted 1 nor 6c could be separated from 6a and 6b by flash
chromatography. Thus, the crude reaction mixture was first
treated with 1,4-benzoquinone to consume unreacted 1 and then
hydrogenated to convert 6c to 6a. Subsequent chromatography led
to isolation of a 1 : 1.6 mixture of 6a and 6b in 79% combined yield
(Table 2, entry 3)."
Absent from the catalytic systems noted in the preceding
paragraph are examples of the intermolecular hydroarylation of
unactivated alkenes with electron-rich arenes such as indoles.
Rather, hydroarylation of alkenes with indoles requires either an
electron-deficient Michael acceptor1 or prolonged heating under
highly acidic conditions.10 We recently reported effective Pt(II)-
catalyzed protocols for the intramolecular hydroarylation of
unactivated alkenes with indoles11,12 and for the intermolecular
hydroalkylation of ethylene with b-diketones.13 On the basis of
these two precedents, we considered that Pt(II) complexes might
also catalyze the intermolecular hydroarylation of unactivated
alkenes with indoles. Indeed, here we report the platinum-
catalyzed hydroarylation of ethylene, a-olefins, and vinyl arenes
with substituted indoles.
A number of styrene derivatives underwent platinum-catalyzed
hydroarylation with 1 in moderate yield (Table 2, entries 4–8).
Noteworthy was that the Markovnikov/anti-Markovnikov (a : b)
selectivity of the Pt-catalyzed hydroarylation of 1 increased from
2.0 : 1 for the hydroarylation of p-methylstyrene to 1 : 5.8 for the
hydroarylation of p-nitrostyrene (Table 2, entries 4–8). A plot of
the log of the Markovnikov/anti-Markovnikov (a : b) ratio versus
the Hammett s-parameter was linear with slope r = 20.98 (see
Supporting Information{), which points to the increasing con-
tribution of the zwitterionic resonance structures B and C with the
Reaction of 1,2-dimethylindole (1), ethylene (50 psi), and a
catalytic amount of [PtCl2(H2CLCH2)]2 (2; 0.5 mol %) in dioxane
at 90 uC for 6 h led to isolation of 3-ethyl-1,2-dimethylindole (3) in
99% yield (eqn (1)).{ The efficiency of the platinum-catalyzed
P. M. Gross Chemical Laboratory, Duke University, Durham,
North Carolina, USA. E-mail: rwidenho@chem.duke.edu;
Fax: +1-919-6601605; Tel: +1-919-6601533
{ Electronic supplementary information (ESI) available: general methods.
See DOI: 10.1039/b607286k
14
increasing electron donating ability of the para substituent.I
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Table 1 Reaction of ethylene with indoles catalyzed by [PtCl2(H2CLCH2)]2 (2) at 90 uC for 3–6 h
Entry
Indole
Cat load (mol %)
Product
Yield (%)a
1
2
3
4
R1 = Me, R2 = H (1)
R1 = Me, R2 = OMe
R1 = Me, R2 = Cl
R1 = Ph, R2 = H
0.05
0.5
0.5
0.5
3
90
99
99
76
5
6
a
R1 = Et, R2 = Ph
R1 = Me, R2 = H
0.5
0.5
86
71
Isolated yield of .95% purity.
In summary, we have developed effective Pt(II)-catalyzed
protocols for the intermolecular hydroarylation of ethylene,
a-olefins and vinyl arenes with indoles. We continue to work
toward the development of more active and more selective
hydroarylation catalysts.
Acknowledgment is made to the NSF (CHE-0304994 and
CHE-0555425), the Camille and Henry Dreyfus Foundation, and
GlaxoSmithKline for support of this research.
Scheme 1
Table 2 Platinum-catalyzed reaction of 1,2-dimethylindole (1) (0.5 M)
with a-olefins and vinyl arenes
Notes and references
{ Control experiments ruled out the possibility of acid-catalyzed back-
ground reactions for the hydroarylation of ethylene, a-olefins, and vinyl
arenes with indoles (see Supporting Information{).
§ Employment of 2 as a catalyst for the hydroarylation of a-olefins or vinyl
arenes led to contamination of the product with small amounts of the
corresponding 3-ethyl indole.
" PtCl4 is also an effective catalyst for the hydroarylation of vinyl arenes
(see Supporting Information{) and for the intramolecular hydroarylation
of alkynes.15
Yield
Conditionsa Product (a + b)b Ratio (a:b)
Entry
R
I We have previously shown that the Pt(II)-catalyzed intramolecular
hydroarylation of alkenes with indoles occurs via outer-sphere attack of the
indole on a Pt-complexes alkene.11
1
2
3
4
5
6
7
8
a
Me
Et
A
A
B
B
B
B
B
B
4
5
6
7
8
9
10
11
88
74
79
55
43
56
51
39
6 : 1
6 : 1
1 : 1.6
1.1 : 1
2.0 : 1
1 : 2.5
1 : 3.1
1 : 5.8
4-C6H4Cl
4-C6H4H
4-C6H4Me
4-C6H4CN
4-C6H4CF3
4-C6H4NO2
1 G. A. Olah, R. Krishnamurti and G. K. S. Prakash, Friedel–Crafts
Alkylationsin Comprehensive Organic Synthesis, ed. B. M. Trost and
I. Fleming, Pergamon Press, Oxford, 1991, vol. 3, pp. 293–339.
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Conditions A: p(propene) = 50 psi, p(butene) = 30 psi, 90 uC,
5 mol% HCl, 14 h. Conditions B: [vinyl arene] = 1 M, 120 uC, 12 h;
the crude reaction mixture was treated sequentially with
p-benzoquinone (0.5 equiv., 45 uC, 7.5 h) and H2 (1 atm) on Pd/C
(25 uC) prior to isolation by chromatography. Isolated yield of
.95% purity.
b
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Chem. Commun., 2006, 3717–3719 | 3719