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Y. Hayashi et al. / Tetrahedron Letters 46 (2005) 681–685
Table 1. a- and c-Benzoyloxylation under several reaction conditionsa
O
O
O
PhCO2Na
additive
I
OBz
+
1
2
3
OBz
Entry
Additive
Equiv
Solvent
Temp. (°C)
Time (h)
Yield 2/%b
Yield 3/%b
1
n-Bu4NHSO4
n-Bu4NBr
BnEt3NCl
1.2
1.2
1.2
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.8
DMF
DMF
23
23
5.5
8
43
0
16
0
2
3
DMF
DMF
23
23
6.5
7
16
47
43
50
21
40
20
14
2
11
29
40
24
55
29
62
51
63
4
n-Bu4NHSO4
n-Bu4NHSO4
n-Bu4NHSO4
n-Bu4NHSO4
n-Bu4NHSO4
n-Bu4NHSO4
n-Bu4NHSO4
18-Crown-6
5
Acetone
CH3CN
t-BuOH
DMSO
THF
40
50
1
6
1
7
50
50
1
8
1
9
50
Reflux
Reflux
2
10
11c
Toluene
Acetone
2
6
a
˚
The reaction was performed with 1 (1.0 equiv), PhCO2Na (2.5 equiv), additive and MS 4 A (200 wt %) in solvent (0.2 M).
b Isolated yield.
c Phenol was isolated in 35% yield.
obtained in 27% and 34% yield, respectively, indicating
caesiumbenzoate is not better nucleophile in this reac-
tion. Instead of n-Bu4NHSO4, however, crown ether
such as 18-Crown-6 was also found to be a suitable
additive, affording the c-adduct 3 predominately. That
is, when 1 was treated with sodiumbenzoate in the pres-
ence of 18-Crown-6 in acetone under reflux, the reaction
proceeded efficiently, providing the c-adduct 3 and the
a-adduct 2 in 63% and 2% yield, respectively, along with
phenol in 35% yield (entry 11).
amounts. The expected products, 2-benzoyloxy-cyclo-
hept-2-en-1-one and 4-benzoyloxy-cyclohept-2-en-1-
one, were obtained in 20% and 15% yield, respectively,
with 2-benzoyloxy-cyclohept-3-ene-1-one being formed
in 41% yield under conditions A (entry 9). Predominant
formation of the c-benzoyloxylated product was
observed under conditions B: 4-benzoyloxy-cyclohept-
2-en-1-one was formed in 58% yield (entry 10). An acy-
clic a,b-enone showed a different profile. a-Benzoyloxy-
lated products were obtained selectively under both
reaction conditions. Under conditions A, 3-benzoyl-
oxy-hept-3-en-2-one was obtained in 72% yield without
c-benzoyloxylated product (entry 11). Under conditions
B, 3-benzoyloxy-hept-3-en-2-one was obtained in 40%
yield along with the a-benzoyloxylated b,c-unsaturated
derivative in 21% yield (entry 12).
As we had found two suitable additives to sodiumbenzo-
ate, that is, n-Bu4NHSO4 (conditions A) and 18-Crown-6
(conditions B), the generality of the reaction under these
two reaction conditions was examined with various a-
halo-a,b-enones, with the results summarized in Table 2.
In the reaction of 2-iodo-3-methyl-cyclohex-2-en-1-one,
three products, that is, 2-benzoyloxy-cyclohex-2-en-1-
one, 4-benzoyloxy-cyclohex-2-en-1-one and 3-benzoyl-
oxy-methyl-cyclohex-2-en-1-one were obtained in 30%,
20% and 19% yield, respectively, under conditions A
(entry 3), while the c- and c0-isomers were obtained
selectively without the a-isomer under conditions B.
Namely, 3-benzoyloxymethyl-cyclohex-2-en-1-one, the
c0-isomer, and 4-benzoyloxy-3-methyl-cyclohex-2-en-1-
one, the c-isomer, were obtained in 68% and 17% yield
(entry 4). When the 3-ethyl derivative was examined,
the a/c-selectivity under conditions A was similar to that
of the 3-methyl derivative, giving three products (entry
5). Reaction is slow under conditions B, affording the
c- and c0-benzoyloxylated product in 46% and 27%
yield, respectively, with a small amount of a-benzoyl-
oxylated product (6%, entry 6). When there is a substi-
tuent at the 4-position, the phenol was obtained in
good yield. That is, 4-tert-butyl-2-iodo-cyclohex-2-en-
1-one was converted into 4-tert-butylphenol in good
yield irrespective of the reaction conditions (entries 7
and 8). In the case of a cycloheptene derivative, the
b,c-unsaturated derivative was obtained in substantial
Not only a-iodoenones, but also a-bromoenone can be
employed, reacting with sodium benzoate under both
reaction conditions (A and B) to afford a- and c-benzoyl-
ated cyclohexenone, though longer reaction time is nec-
essary compared with that of a-iodoenones (entries 13
and 14).
3-Bromo-pent-3-ene-2-one is reported to react with phe-
nol in the presence of K2CO3 to afford 3-phenoxy-pent-
3-en-2-one, a reaction for which the AdSNE mechanism8
has been proposed.4 The present reaction does not pro-
ceed via an AdSNE process, because b,c-unsaturated
derivatives are isolated. The mechanism is shown in
Scheme 1 for the reaction of 2-iodo-cyclohex-2-en-1-
one (1). Sulfate anion (conditions A) and benzoate
anion (conditions B) act as a base to generate the dieno-
late, which reacts with some kind of proton source
such as another cyclohexenone molecule, the acetone
solvent, or the hydrogensulfate anion, affording 2-
iodo-cyclohex-3-en-1-one. 4-Benzoyloxy-cyclohex-2-en-
1-one (2) was obtained by an SN20 benzoyloxylation,
while SN2 benzoyloxylation and isomerization afford
2-benzoyloxy-cyclohex-2-en-1-one (3). In spite of the