Organic Letters
Letter
brings the axial chirality to the molecule. Also, we expect the
charge-transfer complex formed from in-situ-generated iodine
and DMSO to catalyze the conversion of thioketone to simple
ketones via the halogen bond.
Scheme 8. Proposed Catalytic Cycle for 2a and 3a
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
Experimental procedures, characterization data for all
products, NMR spectra (PDF)
Accession Codes
crystallographic data for this paper. These data can be obtained
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
subsequently undergoes ligand replacement by xanthate,
leading to the formation of intermediate B and KI as a
byproduct. The liberated byproduct KI may be oxidized to
iodine by using DMSO. Intermediate B will be converted to
intermediate C by reductive elimination. The intermediate C
will generate thiolate anion intermediate D via base hydrolysis.
There are two possibilities for the formation of product 3
from intermediate D. In path a in Scheme 8, intermediate D
may undergo nucleophilic ring opening of cyclopropane,
followed by Krapcho decarboxylation in the presence of halide
anion in DMSO, by expelling CO2 as a gas to form
intermediate E. Intermediate E then undergoes direct
oxidation by halogen, which leads to the formation of 3.
Alternatively, the addition of a stoichiometric amount of acetic
acid to intermediate D will give intermediate F via rapid
thionation of ketone chemoselectively over the ester.
Intermediate F will be oxidized to thioflavothione 2 by in-
situ-formed halogen. Because of the poor orbital overlap
between two elements that differ significantly in size, the
carbon−sulfur π-bond has high reactivity; also, the enethiol
tautomer is favored to a greater extent than in keto−enol
tautomerism. Upon comparison, the rate of the transformation
from F to 2 is rapid, compared to the rate of the
transformation from E to 3. Finally, compound 2 will be
immediately converted to 3 in the presence of an in-situ-
generated charge-transfer complex. It is important to mention
that we were able to isolate the thioflavothione 2 by
performing this reaction in DMF, instead of DMSO. The
driving force for the rapid conversion of intermediate 2 to 3 is
the CT complex formation between the in-situ-generated
halogen with DMSO. Hence, the formation of both 2 and 3
primarily follows path b in Scheme 8.
In summary, we have disclosed an efficient Cu-catalyzed
domino strategy for the synthesis of 3-alkyl-carbonated
thioflavones via intramolecular ring opening of easily accessible
2′-halosubstituted D−A cyclopropane, using xanthate as a
sulfur surrogate. To the best of our knowledge, this is the first
example that takes advantage of intramolecular D−A cyclo-
propane ring opening reaction via in-situ-generated thiolate
anions, followed by oxidation using I2 that is generated from
waste byproduct KI using DMSO as an oxidant. Furthermore,
this methodology is extended for the domino synthesis of
chemoselective 3-alkyl-carbonated thioflavothione using xan-
thate and AcOH as thionating reagents. This can be a better
alternative for existing thionating reagents. Also, we found that
the substitution of ortho and meta position of phenyl ring
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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G.S. thanks IIT Madras (No. CHY/17-18/847/RFIR/GSEK)
for financial support. N.S. thanks CSIR, New Delhi for a senior
research fellowship. We thank DST and Department of
Chemistry, IIT Madras for Instrumentation facilities.
DEDICATION
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Dedicated to Prof. H. Ila on the occasion of her 75th birthday.
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