374
W. F. Lo et al. / Tetrahedron Letters 48 (2007) 371–375
OEt
O
OEt
Pd(PPh3)2Cl2
dation (DFG) for financial support of this work. Dr. C.
Fischer, Mrs. C. Mewes, Mrs. A. Lehmann, Mrs. S.
Buchholz (all Leibniz-Institut fur Katalyse e.V. an der
¨
Universita¨t Rostock), Dr. D. Go¨rdes, and Mr. E.
Schmidt (all CELISCA) are acknowledged for their
technical and analytical support. Special thanks are gi-
ven to AllyChem Co. Ltd., Dalian, China (www.
bis(pinacolato)diborane (2).
+
PhI
1,4-dioxane/H2O,
K2CO3, microwave,
150 oC, 1.5 h
N
H
N
H
O
BPin
Ph
3a
5 73%
Scheme 2. Suzuki-Miyaura cross-coupling of 3a with PhI.6a
2-position,6,18 while borylation of N-methylindole gave
a mixture of 2- and 3-borylated products in a ratio of
56:44.18a Thus, it is likely that the indole N–H group
is a directing group for the borylation reaction.
References and notes
In most of the reported borylation procedures, the are-
nes are usually used in excess with respect to 2 when
more than one unhindered C–H bond exists in order
to obtain the mono-boronate in good yield.6,18 How-
ever, 2-substituted indoles gave full conversion with high
selectivity towards 7-borylated indoles in the presence of
an equimolar or a slight excess amount of 2 (Table 2, en-
tries 1, 3 and 4). This is an important advantage because
more expensive starting materials may also be further
functionalized through the boronate using our protocol.
It is noteworthy that in principle both boronate groups
in bis(pinacolate)diborane (2) are effective to the bory-
lation reaction and generate only hydrogen as by-product
(Tables 1 and 2). Hence this reaction is a clean, atom
efficient and direct method towards 2,7-disubstituted
indoles.
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As a demonstration for the use of the borylated indoles,
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substituted product 5 in 73% yield under microwave
conditions (Scheme 2).6a
o1062338p; (b) Neumann, H.; Strubing, D.; Lalk, M.;
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Fischer indole synthesis.19
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Clearly, the method presented here provides a more gen-
eral access to this substitution pattern and may contrib-
ute to medicinal chemistry and pharmaceutical industry
in the future.
In conclusion, we have shown the application of the irid-
ium-catalyzed borylation reaction to 2-substituted
indoles. Excellent regioselectivity towards 7-borylated
indoles was observed. In the presence of an excess of
the borylation reagent, 2,4,7-trisubstituted indoles are
obtained preferentially. The scope and limitation of
the catalytic system are demonstrated on indoles with
various functional groups with moderate to excellent
yields. Further functionalization of the 7-borylated
indoles to potentially bioactive compounds is in progress
in our group.
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Acknowledgements
The authors thank the Federal Ministry of Education
and Research (BMBF) and the German Research Foun-