gathered through isolation of intermediates suggests
possible intermediacy of an acylotropic shift during the
de-symmetrization of 1,3-diones.
Financial support of this work by the Council of Scientific
and Industrial Research, INDIA (Grants 01(2121)/07/EMR-II)
and by the Department of Science and Technology, INDIA
(Grants SR/S1/OC-13/2007) is gratefully acknowledged.
PG thanks IIT Madras and SN thanks CSIR for Research
Fellowships.
Fig. 4 Comparison of 6a with known natural products.
contaminants such as sulfur6 or sodium nitrite7 was investigated.
Results from experiments conducted thus far have not shown a
clear correlation between the formation of 6a, 8b and 9b and
presence of these oxidants. Similar oxidation propensities of
disulfide intermediates8 and possible involvement of diketone
derived by-products9 are currently being investigated to gather
more information on this transformation.
Notes and references
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In order to improve the overall yields of reactions depicted
in Schemes 1 and 2, we have attempted to use 2-bromosulfenyl-
benzoyl chloride10 in place of dithiodibenzoylchloride (3).
Trial experiments involving this and the diones 4a, 4b and
10a resulted in comparable yields of 7a, 7b and 13a but
compounds of the type 6a, 8b and 9b were not detected under
this condition. A search for desymmetrization propensities of
1,3-diones has shown that such compounds on reaction with
2-chloroselenobenzoyl chloride can lead to benzoselenophenes.11
To the best of our knowledge, there is no report on the
formation of products such as 6a, 8b and 9b from 1,3 diones
so far. Formation of these products are remarkable and
involves almost six tandem reactions including an unexpected
methylene oxidation. The compound 6a possesses some
composite features of natural products such as longianone,12
trachyspic acid,13 and jatrophone.14 Its comparative display
with these natural products is presented in Fig. 4.
Friedel–Crafts acylation,15 or lithiation followed by
alkylation16 are common methods to functionalize the C-3
position of benzothiophene. Strategies toward 2,3-disubstituted
analogs in general require synthesis of starting materials such as
phenylthioethenes,17 S-substituted mercaptobenzophenones18
or benzyl o-ethynylphenylsulfides19 prior to the cyclization
step. Other notable approaches toward such systems include
(i) a gold-catalyzed cyclization route involving (o-alkynyl
phenyl) sulfides by Nakamura and co-workers,20 and (ii) a
one pot method using arylbromide, an internal alkyne and
sulfur dichloride through the intermediacy of a zirconocene-
benzyne complex, reported by Buchwald and Fang.21 In the
present communication, we have demonstrated a method to
prepare highly functionalized benzothiophenes in just one
synthetic operation from readily available starting materials.
Various functional groups present in these products provide
avenues for further synthetic elaboration to generate new
analogs for biological testing.
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To summarize, a novel one-pot methodology that gives
access to benzothiophenes containing spiroketal, lactone,
carbonyl, hydroxyl and carboxylic acid functionalities is
demonstrated. Formation of some of these products involves
as many as six tandem reactions in one step! Information
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 7131–7133 | 7133