5396
R. Singha, J.K. Ray / Tetrahedron Letters 57 (2016) 5395–5398
Table 2
right side. Thus, after workup with water, we will get the O-acety-
lated product 3.
Acetylation of different arylmethanols.a,b
O
i. KOtBu, DMSO,
Argon, 10 min
OH
n
Ar
O
n
Results and discussion
Ar
ii. EtOAc (1 mL), 10 min
iii. water workup
2a-z
At first we had chosen naphthalen-2-ylmethanol as the model
substrate and treated it with different bases in various solvents
for 10 min and then we added excess amount of ethyl acetate to
the reaction mixture and stirred for the required times. The results
are given in Table 1.
3a-z
OAc
OAc
MeO
OAc
OAc
At first we stirred the substrate 2a with KOtBu (1.0 equiv.) in
DMSO (2 mL) at room temperature for 10 min and then 1.0 mL of
ethyl acetate was added and the progress of the reaction were
monitored by TLC. After 10 min, we observed that the substrate
was vanished and then we isolated the acetylated product 3a in
81% yield. Then we increased the amount of base and found that
it gave 92% of acetylated product with two equivalents of KOtBu
and on further increase of equivalent of base did not affect the
yield of product. Then we varied the solvents and we found that
DMF, DMA and MeCN gave the product in poor yields (Table 1,
entries 4–6). The hydrocarbon solvents benzene and toluene also
resulted the acetylated product in moderate yields (entry 7, 9).
Then we employed different bases and observed that NaOAc,
Na2CO3 and K2CO3 were failed to carry out the reaction. We also
employed NaOtBu and it afforded 2a in 77% of yield. In absence
of KOtBu the starting material remained unreacted. Thus the opti-
mized reaction conditions were: substrate (0.5 mmol), KOtBu
(1.0 mmol), DMSO (2 mL) and stirred at room temperature under
argon atmosphere for 10 min. Then 1.0 mL of EtOAc was added
and stirred for an additional 10 min. Then the reaction mixture
was diluted with water.
After getting the standard reaction conditions we employed dif-
ferent substrates to examine the versatility of the methodology. At
first different aryl-2-ylmethanols were used for the reaction and
the corresponding acetylated products were obtained in moderate
to good yields (Table 2). It was found that the electron rich sub-
strates (Table 2, entries 3b, 3d, 3e, 3g, 3o, 3p) gave slightly higher
yields than the electron poor substrates (entries 3c and 3f). The
halogen containing substrates (entries 3i-3l) gave the products in
moderate yields. The thiophene-2-ylmethanol and furan-2-
ylmethanol afforded the product in lower yields probably due to
the decomposition of the substrates under strong basic conditions.
The biphenyl-2-ylmethanols gave the product in good yields
whereas the (4-nitrophenyl)methanol did not give any acetylated
product due to the decomposition of the substrates as no starting
MeO
3b, Y= 87%
OMe
3d, Y= 92%
3c, Y= 76%
OAc
3a, Y= 92%
OAc
MeO
OAc
OAc
MeO
MeO
MeO
MeO
OMe
3g, Y= 86%
OMe
3e, Y= 88%
OAc
3f, Y= 83%
OAc
F
3h, Y= 84%
OAc
OAc
Cl
Br
Br
Cl
3i, Y= 72%
3j, Y= 60%
3k, Y= 67%
3l, Y= 75%
OAc
OAc
OAc
OAc
MeO
3n, Y= 82%
OMe
3p, Y= 85%
3m, Y= 84%
3o, Y= 94%
OAc
OAc
S
O
OAc
OAc
Br
3q, Y= 65%
3r, Y= 49%
3s, Y= 82%
3t, Y= 83%
OAc
OAc
Ph
OAc
O2N
OMe
OAc
3w, Y= 62%
3v, Y= 0 %
3u, Y= 88%
OAc
Ph
Ph
OAc
Ph
3z, Y= 96%
3x, Y= 86%
3y, Y= 97%
a
Isolate yields.
Reaction conditions: substrate (0.5 mmol), KOtBu (1.0 mmol), DMSO (2 mL) and
stirred at room temperature under argon atmosphere for 10 min. Then 1.0 mL of
EtOAc was added and stirred for an additional 10 min. Then the reaction mixture
was diluted with water.
b
Table 1
Screening of the reaction conditions.a
material was recovered. The propargyl acetate (3w) was formed
in moderate yield where as the cinnamyl alcohol got acetylated
in good yield (3x). The saturated long chain alcohols got acetylated
in quantitative yield (3y and 3z).
Entry
Solvent
Base
Time (min)
Yieldb
1
2
3
4
5
6
7
8
DMSO
DMSO
DMSO
DMF
KOtBu(1)
KOtBu(2)
KOtBu(3)
KOtBu(2)
KOtBu(2)
KOtBu(2)
KOtBu(2)
KOtBu(2)
KOtBu(2)
NaOAc(2)
Na2CO3(2)
K2CO3(2)
NaOtBu(2)
–
10
10
10
30
30
30
30
30
81
92
92
24
18
32
66
37
71
00
00
00
77
00
After successful acetylation of primary alcohols, we wished to
employ the screened reaction condition on different substituted
secondary alcohols to examine the scope of the reaction. When
we applied the standard reaction condition on 1-phenylethanol
(4a), we got the acetylated product only in 34% of yield. Then we
increased the reaction time both in step I and step II and we
observed the increase of yield to 51%. Then this modified reaction
condition was applied on various 2° alcohols and we got the corre-
sponding acetylated products in lower to moderate yields (Table 3).
The electron rich substrates (Table 3, entries 5b, 5c and 5h) gave
the products in slight higher yields than the analogous electron
poor substrates. The 1,2-dihydroacenaphthylen-1-ol afforded
higher yield than the other secondary alcohols.
DMA
MeCN
Benzene
Cy-hexane
Toluene
DMSO
DMSO
DMSO
DMSO
DMSO
9
30
10
11
12
13
14
120
120
120
30
120
a
Reaction conditions: (i) substrate 79 mg (0.5 mmol), base (equivalent), solvent
2 mL, r.t., 10 min; (ii) EtOAc (1 mL), r.t., 10 min, (iii) diluted with water.
b
Isolated yield.