Tin Tetrachloride-Catalyzed Regiospecific Allylic Substitution of Quinone Monoketals
Experimental Section
General Procedure for the Synthesis of Benzofurans
3a–q (3a as Example)
To a stirred solution of 4,4-dimethoxycyclohexa-2,5-dienone
1a (69 mg, 0.45 mmol) and 4,4-bis(methylthio)but-3-en-2-
one 2a (40.5 mg, 0.25 mmol) in dry acetonitrile (2 mL) was
added an acetonitrile solution of SnCl4 (1 mL, c=0.0025
mol/L, 0.0025 mmol) at room temperature. The reaction
mixture was stirred for 10 min to consume the starting mate-
rial 2a as indicated by TLC. The resulting mixture was
poured into saturated aqueous NaCl (10 mL), neutralized
with aqueous NaHCO3, and extracted with CH2Cl2 (3ꢂ
10 mL). The combined organic phase was washed with
water (3ꢂ10 mL), dried over MgSO4 and concentrated
under vacuum. The residue was purified by flash silica gel
chromatography (petroleum ether:ethyl acetate=40:1, v/v)
to give 3a as a white solid; yield: 59 mg (99%).
Scheme 3. Proposed mechanism for the formation of benzo-
furan 3a.
Acknowledgements
We acknowledge NNSFC (21172031/21072027/20972029),
NENU (10JCXK009, 10SSXT140), and the State Key Labo-
ratory of Fine Chemicals (KF1003) for funding support of
this research.
The above transformation represents a tandem al-
lylic substitution, intramolecular cyclization, and elim-
ination of thiol process. The high efficiency and selec-
tivity of 2a in the nucleophilic attack at the a-position
of the carbonyl of intermediate B should be noted.
Besides the strong nucleophilicity of 2, a pseudo-in-
tramolecular[6] process might be involved to well ex-
plain the selectivity although it remains to be clari-
fied. Coordination of SnCl4 to the carbonyls of both B
and 2a can put 2a close to the a-position of 1a
(shaded part in Scheme 3). It facilitates the following
allylic substitution. In fact, it has been found that the
structural nature of the carbonyl in 2 plays a key role
for the reaction (Table 2, entries 1–17 versus
entry 18).[16] From the point of view of the pseudo-in-
tramolecular process, it is easy to understand that 2f
is sluggish in the above process due to the inefficient
coordination of its bulky carbonyl group with an un-
satisfying conformation (Table 2, entry 18).[13]
In conclusion, a new allylic substitution of quinone
monoacetals has been developed. Accordingly,
a range of substituted benzofurans was synthesized in
high to excellent yields from quinone monoacetals
and ketene dithioacetals via a formal [3+2]cycloaddi-
tion under mild conditions. The reaction is anticipated
to involve a pseudo-intramolecular process which
leads to high regioselectivity and efficiency of the re-
actions. Additionally, the method was extended to
allow the synthesis of bioactive coumestans in a single
step from the reaction of quinone monoacetals and vi-
nylogous thioesters. Further studies on mechanism
and applications are in progress.
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