Organic Letters
Letter
Hydroarylation of cyclohexene and cyclopentene provided low
yields of the products (20 and 21).
Our optimized conditions were ineffective when employing
substrates with basic functional groups (i.e., pyridyl), which
prompted us to probe the mechanism of the reaction (Table 2).
excellent yields while avoiding harsh conditions and wasteful use
of reagents. We are currently performing mechanistic studies in
an effort to elucidate the active catalyst and reactive
intermediates.
ASSOCIATED CONTENT
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a
S
* Supporting Information
Table 2. Mechanistic Probe
The Supporting Information is available free of charge on the
Experimental details, characterization data, and NMR
spectra for new compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
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acid source
(mol %)
ZnBr2
(mol %)
entry
yield of 1a (%) yield of 1b (%)
Notes
b
1
TMSCl (5)
TMSCl (5)
TMSCl (5)
HCl(g)
1
1
1
1
0
0
0
0
c
2
d
3
0
0
The authors declare no competing financial interest.
4
5
80
0
12
0
ACKNOWLEDGMENTS
HCl(g)
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a
Yield was determined by uncalibrated GC/MS analysis of the crude
Financial support from Loyola University Chicago is gratefully
acknowledged. We thank James Devery (Loyola) for insightful
discussions.
b
reaction mixture relative to an internal standard. Reaction performed
with 5 mol % of di-tert-butylpyridine. Reaction performed with 1
equiv of K2CO3. Reaction performed with 10 mol % of pyridine at 60
c
d
°C.
REFERENCES
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(1) (a) Perego, C.; Ingallina, P. Catal. Today 2002, 73, 3. (b) Perego,
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Utilizing bases such as 2,6-di-tert-butylpyridine, potassium
carbonate, and pyridine completely disrupted any reactivity
(entries 1−3). Increased temperatures under basic conditions
were also ineffective at promoting the reaction (entry 3).
Removal of the TMSCl and introduction of gaseous HCl
provided comparable results to our optimized conditions (entry
4); however, HCl(g) alone did not provide the hydroarylation
products (entry 5). In addition, other Brønsted acids were tested
and afforded the products with diminished yields compared to
3). These combined results suggest that the TMSCl/ZnBr2
cocatalyst system likely operates through both a Brønsted acid
and Lewis acid mechanism. The TMSCl presumably releases
HCl to act as the Brønsted acid; however, the Lewis acidic ZnBr2
is required to complete the reaction.22 Further investigations to
determine the mechanism and the identity of the active catalyst
are currently underway and will be reported in due course.
Finally, to demonstrate the practicality of this process, the scale
of the hydroarylation reaction was increased. On a 5 g scale, the
hydroarylation of styrene with 2,6-dimethylphenol gave product
6 in 82% yield (Scheme 4). This yield is comparable to the small-
scale reaction in Scheme 2, which demonstrates that the process
is scalable.
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In conclusion, we have developed a low-cost, mild, and scalable
catalyst system for the efficient hydroarylation of olefins. Our
method provides valuable diarylmethine products in good to
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Scheme 4. Scaled-up Hydroarylation Reaction
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C
Org. Lett. XXXX, XXX, XXX−XXX