Organic Letters
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yield (Table 1, entry 18). A slight erosion of the yield was
gained when using 3.0 equiv of AgOAc (Table 1, entry 19).
Decreasing the amount of K2CO3 to 3.0 equiv resulted in a
lower product yield (Table 1, entry 20). Changing the amount
of Se to 2.0 or 4.0 equiv did not produce better results (Table
1, entries 21 and 22). In addition, only a trace amount of 2a
was observed when the reaction was carried out without TBAI
(Table 1, entry 23). TBAI may act as a phase transfer catalyst,
increasing the dissolution of selenium and K2CO3 in the
nonpolar solvent DCM. In the absence of silver salt or base, no
product was obtained (Table 1, entries 24 and 25). Removal of
the additive led to a 63% yield (Table 1, entry 26).
TMEDA, at 60 °C in DCE for 12 h, providing the desired 3a in
80% yield (eq 2).
Encouraged by the above results, we investigated the
substrate range of the cyclization reaction. As shown in Figure
2, a variety of diynes 1 were tested, and the corresponding
With the optimized reaction conditions in hand, the
substrate scope of diynes 1 for the synthesis of cyclopenta[c]-
thiophenes 3 was examined (Figure 3). Various functionalized
Figure 2. Substrate scope of diynes 1 to synthesize cyclopenta[c]-
selenophenes 2. Reaction conditions: 1 (0.2 mmol), Se (0.6 mmol),
AgOAc (0.4 mmol), K2CO3 (0.8 mmol), Co(OAc)2·4H2O (0.02
a
mmol), TBAI (0.3 mmol), DCM (2.0 mL), air, isolated yields. 60
°C.
Figure 3. Substrate scope of diynes 1 to synthesis cyclopenta[c]-
thiophenes 3. Reaction conditions: 1 (0.2 mmol), S8 (0.2 mmol),
AgOAc (0.4 mmol), TMEDA (0.4 mmol), Cu(OAc)2 (0.02 mmol),
DCE (2.0 mL), air, isolated yields.
cyclopenta[c]selenophene products 2a−2r were smoothly
synthesized in 39−93% yields. Notably, various functional
groups, including ester, nitrile, ketone, amide, sulfone, and silyl
ether, were well tolerated under the reaction conditions.
However, when 1,6-heptadiyne was used, we did not observe
the formation of corresponding product 2s. In further
investigations of the applicability, we found that diyne with a
phenyl substituent at one triple bond failed to give the desired
products 2t under standard conditions, and the staring material
was recovered. It indicates that terminal diacetylenes are
indispensable to the formation of cyclopenta[c]selenophenes.
Subsequently, we tried to apply this method to the
cyclization reaction of diyne 1a with elemental sulfur to
synthesize cyclopenta[c]thiophene. Unfortunately, only a trace
amount of 3a was detected (eq 1). In order to improve the
yield of 3a, different reaction parameters, such as temperature,
silver salts, bases, additives, and solvents, were screened (see
result for the preparation of 3a was to use 1.0 equiv of S8, 10
mol % Cu(OAc)2, 2.0 equiv of AgOAc, and 2.0 equiv of
diynes could successfully react with elemental sulfur under
standard conditions, offering the desired thiophene products in
moderate to good yields (3a−3v). The functionalities such as
ester, nitrile, ketone, amide, sulfone, and silyl ether, were all
well compatible. Similarly, neither 1,6-heptadiyne nor diyne
with a phenyl substituent at one triple bond could deliver the
corresponding thiophene products by this method (3w, 3x).
We next investigated the potential synthetic utility of these
synthetic strategies. First, gram-scale reactions were performed,
and we obtained the corresponding products 2a and 3a in 64%
and 73% yields, respectively (Scheme 2a). Then, further
derivatization of cyclopenta[c]selenophene 2a was carried out.
For example, 2a could react with NBS or NIS to give its 2,5-
dibromo or diiodo product 4a or 5a in 82% and 84% yields,
respectively.2b Besides, the ester groups of 2a could be reduced
to hydroxyl groups by lithium aluminum hydride, providing 6a
5913
Org. Lett. 2021, 23, 5911−5916