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Organic & Biomolecular Chemistry
Page 4 of 5
ARTICLE
Journal Name
carbonyl group, was used. The corresponding product 4t was
not formed.
Based on above mechanistic studies, a reasonable reaction
mechanism was proposed (Scheme 5). Initially, acid catalyzed
Conflicts of interest
There are no conflicts to declare.
DOI: 10.1039/C9OB01422E
intramolecular cyclization of
2 occurred, after which
Acknowledgements
The project was supported by the Fundamental Research Funds
for the Central Universities (KYZ201751) and Nanjing
Agricultural University.
dehydration reaction and hydrogen atom transfer happened to
afford the key intermediate B. When R1 is an alkyl group, B can
release a H+ to form intermediate C, which can be successfully
captured by 1,3,5-trimethoxylbenzene via 1,6-conjugate
addition. To some extent, formation of 4a from intermediate B
can be excluded since when substrate 2t (R1 = phenyl) was used,
the 1,6-conjugate addition reaction can’t occur. In the absence
Notes and references
1
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of 1,3,5-trimethoxylbenzene,
B
will then convert to
intermediate D along with elimination of H+ which enters the
next catalytic cycle. Finally, D was oxidized by NBS to form
benzofuran derivatives 3. It is worth noting that during the
oxidation step, one equivalent of HBr was formed which could
also promote the cyclization reaction.
2
3
See selected examples: (a) Z. L. Shen, K. K. K. Goh, H. L.
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work, 2,3-unsaturated cyclohexanone was used as starting
material and stoichiometric amount of PTSA was required to
promote the reaction. Thus, a more general method that uses
a cyclohexanone as starting material for the de novo synthesis
of benzofurans, is in high demand..
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Experimental
General procedure for the synthesis of benzofuran derivatives
Procedure for the synthesis of 3a-3r
A Schlenk tube with a magnetic stir bar charged with 2-hydroxy-1,4-
diones 2 (0.20 mmol), trifluoroacetic acid (0.04 mmol, 0.2 equiv.),
1,2-dichloroethane (DCE, 2.0 mL) and N-Bromobutanimide (NBS,
0.30 mmol, 1.5 equiv.). The reaction mixture was then heated to 80
oC and stirred for 6 hours. The reaction mixture was then allowed to
cool to ambient temperature and all of the volatiles were removed
under vacuum, the crude product was purified on flash
chromatography, eluting with petroleum ether/ethyl acetate, to
provide substituted benzofuran 3.
4
Procedure for the synthesis of 3t-3aa
5
6
A Schlenk tube with a magnetic stir bar charged with 2-hydroxy-
1,4-diones 2 (0.20 mmol), trifluoroacetic acid (0.04 mmol, 0.2
equiv.), 1,2-dichloroethane (DCE, 2.0 mL) and N-
Bromobutanimide (NBS, 0.30 mmol, 1.5 equiv.). The reaction
mixture was then heated to 130 oC and stirred for 36 hours. The
reaction mixture was then allowed to cool to ambient
temperature and all of the volatiles were removed under
vacuum, the crude product was purified on flash
chromatography, eluting with petroleum ether/ethyl acetate,
to provide substituted benzofuran3.
Conclusions
In summary, we have developed an efficient one-pot protocol
for the synthesis of benzofuran derivatives starting from 2-
hydroxy-1,4-diones. The reaction features easily available
starting materials, simple reaction conditions and broad
substrate scope. Further application of these novel 2-hydroxy-
1,4-diones in the synthesis of highy functionalized furans and 2-
methylene-2,3-dihydrofuran derivatives were underway in our
laboratory.
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