Organic Letters
Letter
room temperature (Table 1, entries 1−6). To our delight, 10
mol % of AgSbF6 catalyst provided the desired meta-
Scheme 2. Substrate Scope for O-tethered
Cyclohexadienones
a b
,
a
Table 1. Optimization of Reaction Conditions
b
entry [Ag] catalyst mol %
solvent
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
time (h) yield (%)
1
2
3
4
5
6
7
8
AgSbF6
AgNTf2
AgBF4
AgOTf
PhCO2Ag
AgPF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
10
10
10
10
10
10
10
15
5
12
12
12
12
12
12
1
45
<10
12
<10
<10
11
63
78
c
1
9
CH2Cl2
CH2Cl2
1
57
10
11
12
13
14
15
2.5
1
1
<10
44
15
15
15
15
15
CH2Cl2 at 50 °C
ClCH2CH2Cl
THF
1,4-dioxane
CH3CN
1
54
1
<5
a
Reaction conditions: 1 (0.3 mmol), AgSbF6 (15.1 mg, 15 mol %) in
1
1
<10
<5
CH2Cl2 (0.1 M) at room temperature under a N2 atmosphere.
b
c
Isolated yields. Starting material was decomposed.
a
Reaction conditions: 1a (0.12 mmol) and [Ag] catalyst in 0.1 M
b
solvent at room temperature under a N2 atmosphere. Isolated yields.
c
substituted phenol 2m in 58% yield. Unfortunately, substrates
with phenyl and methoxy substituents at the quaternary carbon
center and a methyl substituent at the α-position of the
cyclohexadienone were ineffective and decomposed during the
course of the reaction (entries 2n−2p). Interestingly, the
treatment of silyl ether 1q under optimized conditions gave 2-
benzoxepine 3 in 52% yield via an aromatization/desilylation/
oxa-Michael addition sequence (Scheme 3a). A similar result
Further increase in catalyst loading did not influence the reaction
yield.
substituted phenol 2a in higher yield (45%) than other
catalysts (entry 1). Additional optimization revealed that the
starting material is completely consumed within 1 h to afford
2a in 63% yield (entry 7). Increasing the catalyst loading led to
a further increase in the reaction yield (entry 8). However,
decreasing the catalyst loading or increasing the temperature
was found to be inferior in terms of yield (entries 9−11). The
effect of other solvents was also examined. Moderate to lower
yields were observed in all cases (entries 12−15). Other
transition-metal catalysts were ineffective under standard
all, the annulation/aromarization progressed very efficiently
with 15 mol % AgSbF6 catalyst in CH2Cl2 solvent at room
temperature (entry 8). The structure and regioselectivity of the
compound 2a was confirmed by NMR analysis and X-ray
crystallography.
Scheme 3. Other Miscellaneous Transformations on O-
Tethered Cyclohexadienones
With the optimal reaction conditions in hand, the scope of
various O-tethered cyclohexadienones 1 was investigated, and
the results are summarized in Scheme 2. With the substituent
at the prochiral carbon center as methyl, ethyl, or n-butyl, the
reactions proceeded smoothly in high yields (74−78%, entries
2a−2c). All two-, three-, and four-substituted aryl rings gave
the corresponding products in good yields (2d−2k). However,
the sterically bulky ortho substituent and the strong electron-
donating para substituent on the phenyl ring afforded the
corresponding products 2e and 2h in moderate yields. The
heteroaryl ring also had a similar effect on the rearomatization
reaction and gave the desired product 2l in 70% yield.
Pleasingly, the aliphatic substituent on alkyne reacted well
under standard conditions to give the corresponding meta-
was observed with acetate 1r in 56% yield. The reaction of 1a
in the presence of MeOH (4 equiv) under standard reaction
conditions afforded a mixture of the desired product 2a and
the methoxy product 2a′ in 71 and 18% yields, respectively,
due to the ketalization of the carbonyl group with methanol
(Scheme 3b).
On the basis of the above experimental results and related
literature reports,14d,15 a plausible reaction mechanism is
proposed, as depicted in Scheme 4a. The highly alkynophilic
Ag(I) catalyst undergoes complexation with alkyne 1a to
generate a (η2-alkyne)silver intermediate A, which leads to the
318
Org. Lett. 2021, 23, 317−323