Journal of the American Chemical Society
Page 4 of 5
The products shown refer to products upon D2O quenching
medicinal interest and benzodipyrrole of materials interest.
1
2
3
4
5
6
7
8
(except in entry 6), while the reaction yield and product structures
The present work not only adds to the synthetic repertoire of
c
,
dimetallic compounds21 22 but also presents a rare example of
were determined for the corresponding protio compounds. The
C2/C3 regioselectivity (when applicable) for the major product
the control of regioselectivity upon electrophilic trapping by
the use of uncatalyzed or transitionꢀmetal catalyzed reaction
conditions.5–8 The reaction mechanism where two metals
cooperatively lower the energy barrier of the AꢀtoꢀB
cyclization, and the structural and synthetic chemistry of the
bimetallic intermediate are intriguing subjects for future
studies.
d
was >99% for all entries. The yield for the major product is
based on pure isolated protio product, and the yields of the
byproducts are based on either isolation, GLC, or NMR analysis. e
f
nd = not detected. Deuterium was incorporated 100% at C2 and
91% at C3. g The reaction proceeded in the presence of 1 equiv of
CuCN•2LiCl, then allyl bromide was added.
9
Interestingly,
the
reaction
of
B2
with
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chlorotrimethylstannane19 occurred selectively at C2 to give a
2ꢀstannylindole in good yield (entry 5). Chlorotrimethylsilane
gave a C2ꢀsilylation product in only 9% yield. This and the
reactivity described above suggest that the carbonyl addition
and the stannylation reactions are not simple nucleophilic
reactions but occur through electron transfer.20
ASSOCIATED CONTENT
Supporting Information
Experimental procedures and physical properties of the
compounds. This material is available free of charge via the
Finally, we discuss the structure of the zinc intermediates as
correlated to the reactivity and regioselectivity of the observed
reactions. The crystal structure of a structurally similar 2,3ꢀ
dialuminoindole is known, for which we can draw the
resonance scheme shown in Figure 1a.2 We can similarly
consider a dimeric structure for B1 in Figure 1b, where ZnCl2
groups are coordinated to the indole πꢀsystem to form a
zwitterion, where the C3ꢀcarbon is tetrahedral while the C2ꢀ
AUTHOR INFORMATION
Corresponding Author
*laur@chem.s.uꢀtokyo.ac.jp; nakamura@chem.s.uꢀtokyo.ac.jp
Author Contributions
The manuscript was written with contributions from all authors.
All authors have given approval to the final version of the
manuscript.
carbon is trigonal. Such
a
vicinal tetragonal/trigonal
coordination is also known for a 1,2ꢀdimagnesiobenzene
tetramer [(C6H4Mg)4], which is not
a very reactive
ACKNOWLEDGMENT
nucleophile.18 We ascribe the low nucleophilicity of B1 (e.g.,
to carbonyl compounds) to such a dimeric structure where the
potentially nucleophilic C3ꢀcarbon is coordinated to two Lewis
acidic metal atoms and hence is deactivated. When transitionꢀ
metal catalysis is involved, the trigonal C2ꢀcarbon reacts
preferentially with the catalyst to form a new C–C bond at C2
(e.g., Table 1, entry 3 vs. 4).
We thank MEXT for financial support (the Strategic Promotion
of Innovative Research, JST, and GrantꢀinꢀAid no. 15H05754 to
E.N.). We thank Takenari Sato and Shusuke Ochi for help with
several experiments.
REFERENCES
When we used only 1 equiv of PhZnBr, the cyclization
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to give a zincate, as shown in Figure 1c. The C3ꢀcarbon in B2
is expected to be more nucleophilic than the C3ꢀcarbon in B1
as is experimentally observed (cf. Table 2).
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(
6
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(
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Subsequent electrophilic treatment provides
a modular
approach to expeditious synthesis of a variety of indoles,
including 2,3ꢀsubstituted derivatives, indenoindolone of
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