Selective mono-acylation of 1,2- and 1,3-diols using (α,α- difluoroalkyl)amines

Article abstract of DOI:10.1016/j.tet.2010.08.029

In the reaction of N,N-diethyl-α,α-difluorobenzylamine (DFBA) with 1,2- or 1,3-diols, selective mono-benzoylation occurs to afford mono-esters of the diols in good yield. The reaction is completed under mild conditions in a short reaction time. Further, prim-, sec-, and tert-diols and catechol can be converted to the corresponding mono-benzoates. DFBA is used for the protection of the hydroxy group in sugars. The selective mono-nicotinylation, formylation and pivaloylation of diols are also performed by using the corresponding difluoroalkylamines.

Full text of DOI:10.1016/j.tet.2010.08.029

Tetrahedron 66 (2010) 7939e7945
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Tetrahedron
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Selective mono-acylation of 1,2- and 1,3-diols using (a,a-difluoroalkyl)amines
*
Natsumi Wakita, Shoji Hara
Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Accepted 10 August 2010
Available online 14 August 2010
In the reaction of N,N-diethyl-a,a-difluorobenzylamine (DFBA) with 1,2- or 1,3-diols, selective mono-
benzoylation occurs to afford mono-esters of the diols in good yield. The reaction is completed under
mild conditions in a short reaction time. Further, prim-, sec-, and tert-diols and catechol can be converted
to the corresponding mono-benzoates. DFBA is used for the protection of the hydroxy group in sugars.
The selective mono-nicotinylation, formylation and pivaloylation of diols are also performed by using the
corresponding difluoroalkylamines.
Keywords:
N,N-Diethyl-a,a-difluorobenzylamine
Mono-benzoylation
Diols
Ó 2010 Elsevier Ltd. All rights reserved.
Cyclic amide acetal
1. Introduction
2. Results and discussion
Acylation of alcohols is a fundamental and important organic
reaction; that has been frequently used for the protection of alcohols
in both simple and complex molecules. Although many acylation
methods are already known, a new and more efficient method is
required.1 Recently, we reported the selective fluorination of alco-
2.1. Benzoylation of alcohols with DFBA
As an acylation reagent, N,N-diethyl-a,a-difluorobenzylamine
(DFBA)2d,3 was used instead of DFMBA because it reacts with
alcohols to afford benzoyl esters. Initially, the reaction of DFBA
with 1-decanol (1a) was examined (Table 1). When the reaction
was carried out at 0 ꢀC for 30 min using 1.1 equiv of DFBA to 1a,
hols using a new fluorination reagent, N,N-diethyl-a,a-difluoro-m-
methylbenzylamine (DFMBA).2 In the reaction, a relatively high
temperature was required (>100 ꢀC), and at a lower temperature,
a significant amount of an ester (2) derived from alcohol (1) and
DFMBA was formed as a by-product. From these results, it can be
presumed that the formation of adduct (4) in the reaction of 1 and
DFMBA is fast, but the subsequent fluorination step is slow and 2
Table 1
Benzoylation of alcohols with DFBAa
is formed by quenching 4 with water. Therefore, we applied a,a-
difluoroalkylamines for acylation of the alcohols by carrying out the
reaction under mild conditions (Scheme 1).
PhCF2NEt2 (DFBA
)
R-OH
1
R-F
3
R-OBz
2
+
CH2Cl2,0.5 h
ReOH
Temp (ꢀC)
DFBA/ReOH
Yield (%)
2b
3c
+ R-F
3
Ar-CONEt2
O-R
slow
1-Decanol 1a
0
20
40
0
1.1
1.1
1.1
2.0
1.5
2.0
2.0
1.1
1.5
2.0
72
77
74
97
38 (43)
73 (20)
59 (22)
46 (24)
73 (11)
94 (4)
0
F
5
22
0
0
0
0
0
0
0
R
O
ArC=NEt2
4
-HF
fast
+ ArCF NEt
R-OH
1
2
2
ArC NEt2
4-tert-Butylphenol 1b
Cyclododecanol 1c
20d
20e
40e
0
DFMBA
F
H2O
Ar: m-Tolyl
OR
ArC=O 2
20
40
Scheme 1. Reaction mechanism in the fluorination of alcohols with DFBA.
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2 for 0.5 h.
Isolated yield based on 1 used. In parentheses, recovered 1.
GC yield.
The reaction time is 1 h.
The reaction time is 3 h.
b
c
d
e
* Corresponding author. Tel./fax: þ81 11 706 6556; e-mail address: shara@
eng.hokudai.ac.jp (S. Hara).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.029

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N. Wakita, S. Hara / Tetrahedron 66 (2010) 7939e7945
decyl benzoate (2a) was obtained in 72% yield without the for-
mation of decyl fluoride (3a). At 20 ꢀC, the yield of 2a increased
to 77%, but the formation of 3a (5%) was also observed. At 40 ꢀC,
a significant amount of 3a (22%) was formed. These results sug-
gested that the fluorination of 1a proceeds at temperatures
higher than 0 ꢀC and can be prevented by carrying out the re-
action at temperatures below 0 ꢀC. Consequently, 2a could be
obtained in 97% yield without the formation of 3a by carrying out
the reaction at 0 ꢀC using 2 equiv of DFBA. The benzoylation of 4-
tert-butylphenol (1b) and cyclododecanol (1c) is slow, and
a higher reaction temperature (20e40 ꢀC) was required. How-
ever, the fluorination of these substrates is non-feasible or slower
than that of 1a, and the corresponding benzoate (2b) or (2c) was
obtained without the formation of the fluoride (3b) or (3c) under
these conditions.
Table 2
Mono-benzoylation of diols with DFBAa
Entry
Substrate
Temp (ꢀC)
Product
Yield (%)b
84c (5)
HO
HO
OH
1
20
OBz
6a
5a
5b
2d
3
20
20
82c (4)
94 (4)
HO
OBz
HO
HO
OH
OH
6b
HO
OBz
5c
6c
OBz
OH
OBz
OH
OH
OH
4e
20
40
70c (12)
71 (0)
2.2. Mono-benzoylation of diols
5d
6d
Selective mono-benzoylation of diols is useful in organic syn-
thesis, and many methods have been reported.4 In the fluorination
of 1,2- and 1,3-diols with DFMBA, selective mono-fluorination
occurred through a cyclic intermediate and acylated fluorohydrins
were obtained.2c Therefore, we applied DFBA to the selective
mono-benzoylation of diols.5 When prim-diols were used, the
reaction was completed at 20 ꢀC and the corresponding mono-
benzoylated products were obtained in good yields (entries 1e4 in
Table 2). With cyclic diols, the reaction was carried out at 40 ꢀC to
afford mono-benzoates in good yields (entries 8e10). The reaction
of DFBA with diols is fast and is applicable to the mono-benzoy-
lation of less-reactive catechol and the sterically hindered pinacol
(entries 7 and 11). Even when 2 equiv of DFBA to the diols was used,
mono-benzoates were obtained selectively (entries 6e11). Fur-
thermore, from the isolated mono-benzoate (6j), the di-benzoate
(7j) was obtained in good yield under the mono-benzoylation
conditions (entry 12).
Therefore, the selectivity observed in the mono-benzoylation of
diols with DFBA is not attributed to the steric hindrance generated
in the second benzoylation but to the reaction mechanism that
includes a cyclic intermediate.8 As in the case of the fluorination
reaction of diols with DFMBA, a cyclic amide acetal (8) must be
initially formed in the reaction of diol 5 with DFBA.2c The amide
acetal 8 exists stably under the conditions and changes to mono-
benzoate 6 upon the addition of water while excess DFBA is
decomposed to inert N,N-diethylbenzamide by the addition of
water. Therefore, the benzoylation of 6 to di-benzoate 7 scarcely
occurred during the reaction, and 6 was obtained selectively
(Scheme 2).
Generally, after the aqueous work-up, only mono-benzoate 6
was obtained and the presumed cyclic intermediate 8 could not be
isolated. However, in the reaction of diethyl tartrate 5e with DFBA,
the corresponding amide acetal 8e was isolated, and it changed to
mono-benzoate 6e under acidic conditions (Scheme 3).
Next, we examined the regioselectivity in the benzoylation of
unsymmetrical diols. With 1,3-butandiol (5l) having prim- and sec-
alcohol, regioselectivity was not observed, and 3-hydroxybutyl
benzoate (6l) and 4-hydroxybut-2-yl benzoate (6l0) were obtained
as a 1:1 mixture. On the other hand, in the reaction with 4-methyl-
2,4-pentandiol (5m) having sec- and tert-alcohol, the benzoylation
selectively occurred at sec-alcohol to afford 4-hydroxy-4-methyl-
but-2-yl benzoate (6m) in 83% yield (Scheme 4).9
EtOOC
EtOOC
EtOOC
EtOOC
5
OH
6e
OH
5e
6f
40
91 (0)
HO
HO
OH
OBz
6f
5f
7f,g
20
40
86 (2)
92 (3)
5g
6g
HO OH
OH
5h
OH
OH
5i
OH
HO OBz
OBz
6h
OH
8f
OBz
6i
9f
40
40
87 (5)
95 (0)
OH
OH
OH
OBz
OH
10f
6j
5j
OH
OH
OBz
OH
11f
40
40
89 (4)
5k
6k
OBz
OBz
12f
6j
99
7j
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2 for 0.5 h
using 1.1 equiv of DFBA to substrate.
b
Isolated yield based on substrate used. In parentheses, yield of dibenzoate
obtained by GC.
c
1H NMR yield.
The reaction time is 3 h.
The reaction time is 5 h.
2 equiv of DFBA to the substrate was used.
The selective protection of one hydroxy group in sugars is im-
portant for their transformation to oligosaccharide.10 Therefore,
we applied the present benzoylation reaction to sugars. When
d
e
f
g
The reaction time is 1 h.
methyl 5-O-benzoyl-
action with DFBA, selective mono-benzoylation occurred to afford
methyl 3,5-di-O-benzoyl- -ribofuranose (10) and methyl 2,5-di-
b-D-ribofuranose (9) was subjected to the re-
b-D

N. Wakita, S. Hara / Tetrahedron 66 (2010) 7939e7945
7941
2.3. Acylation of diols with various a,a-difluoroalkylamines
(CH2)n
O
(CH2)n
R
R
R
R
(CH2)n
R
R
H2O
DFBA
NEt2
OH2
(CH2)n
As various difluoroalkylamines can be prepared from amides
in two steps,3 the present mono-benzoylation reaction of diols
can be extended to other acylation reactions. The selective mono-
nicotinylation, formylation and pivaloylation as well as 3-
methylbenzoylation of diols were achieved by using N-(difluoro
O
Ph
-2HF
O
O
HO
OH
Ph
NEt2
5
8
(CH )
(CH )
2 n R
R
2 n R
R
R
R
(pyridin-3-yl)methyl)-N,N-diethylamine,
N-(difluoromethyl)mor-
-H
pholine, N-(1,1-difluoro-2,2-dimethylpropyl)pyrrolidine and DFMBA
as shown in Table 3.
O
Ph
O
OH2
O
Ph
O
O
BzO
OH
6
H
n= 0 or 1
Scheme 2. Reaction mechanism in mono-benzoylation of diols with DFBA.
Table 3
Acylation of diols with various
a
,
a
-difluoroalkylaminesa
Alcohol
R2NCF2R0
Product
Yield (%)b
88 (0)c,d
EtOOC
COOEt
OH
CF2NEt2
1MHCl / THF
20 °C, overnight
DFBA
N
6e
5h
O
O
5e
OCO
20 °C, 10 min
31%
N
Ph NEt2
8e
88%
16
CF2NEt2
Scheme 3. Isolation and reaction of cyclic amide acetal 8e.
OCO m-Tol
5c
5i
92 (8)c,d
HO
17a
DFMBA
OH
OBz
OH
OH
OH
DFBA
+
BzO
HO
HO
1
87 (4)c,d
HO
DFMBA
0 °C, 0.5 h
5l
6l
6l'
OCO m-Tol
17b
1
:
79%
OBz
DFBA
20 °C, 0.5 h
HO
OH
5j
82 (4)
5m
HCF2N
O
6m
83%
OCOH
Scheme 4. Benzoylation of unsymmetrical diols with DFBA.
18
t
OCOBu
O-benzoyl-
With methyl
methyl 3-benzoyl-4,6-O-benzylidene-
was obtained in 54% yield with minor products of 2-benzoyl-4,6-O-
benzylidene- -glucopyranoside (14) (18%) and dibenzoate (15)
(6%) (Scheme 5).
b
-
D
-ribofuranose (11) in 34% and 38% yields, respectively.
4,6-O-benzylidene- -glucopyranoside (12),
-glucopyranoside (13)
HO
b-D
b-D
19
tBuCF2N
5m
89 (0)c
OH
b-D
tBuCOO
20
19:20 = 4:1
a
If otherwise not mentioned, the reaction was carried out in CH2Cl2 at 20 ꢀC for
0.5 h using 1.1 equiv of difluoroalkylamine to substrate.
BzO
OMe
BzO
OMe BzO
+
OMe
O
O
O
b
Isolated yield based on substrate used. In parentheses, yield of diacylated
DFBA (2.0 eq)
40 °C, 0.5 h
product.
c
2 equiv of difluoroamine to substrate was used.
The reaction was carried out at 40 ꢀC.
d
HO OH
9
BzO OH
HO OBz
11 38%
10 34%
Ph
Ph
O
O
HO
3. Conclusion
O
DFBA (1.2 eq)
40 °C, 0.5 h
OMe
The selective mono-benzoylation of 1,2- or 1,3-diols was
achieved by using N,N-diethyl-a,a-difluorobenzylamine (DFBA).
HO
12
The reaction was completed under mild conditions in a short
reaction time, and prim-, sec-, and tert-diols and catechol could
be converted to the corresponding mono-benzoates. It was
shown that the reaction proceeded through a cyclic amide ac-
etal. The selective mono-nicotinylation, formylation and piv-
aloylation of diols were also performed by using the
corresponding difluoroalkylamines.
Ph
O
O
O
O
O
O
OMe
OMe
+
+ Dibenzoate
15
HO
BzO
BzO
18%
HO
13
14
54%
6%
Scheme 5. Mono-Benzoylation of sugars with DFBA.

7942
N. Wakita, S. Hara / Tetrahedron 66 (2010) 7939e7945
4. Experimental
and the yield of dibenzoate was determined by GC (5%). Pure
6a was obtained by column chromatography (silica gel/
4.1. General
hexane:EtOAc¼2:1); IR (neat) 3424, 2952, 1719, 1277 cmꢂ1. 1H NMR
d
8.08e8.06 (m, 2H), 7.60e7.56 (m, 1H), 7.48e7.44 (m, 2H),
The IR spectra were recorded using a JASCO FT/IR-410. The 1H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded in
4.49e4.47 (m, 2H), 3.99e3.95 (m, 2H), 2.07 (t, J¼5.9 Hz, 1H). 13C
NMR
d 166.93, 133.12, 129.73, 129.60 (2C), 128.33 (2C), 66.56, 61.17.
CDCl3 on a JEOL JNM-A400II FT NMR and the chemical shift, d, were
referred to TMS. The EI and ESI high-resolution mass spectra were
measured on a JEOL JMS-T100GCV. DFMBA was donated from
Mitsubishi Gas Chemical Company, INC. DFBA, N-(difluoromethyl)
morpholine and N-(1,1-difluoro-2,2-dimethylpropyl)pyrrolidine
were prepared according to the previously reported procedures.3
N-(Difluoro(pyridin-3-yl)methyl)-N,N-diethylamine was prepared
from N,N-diethyl nicotinamide according to the literature (bp
52e54 ꢀC/0.1 mm Hg).3 They were stored in a Teflon bottle under
N2. The small scale reaction can be carried out using glasswares, but
use of Teflon wares is recommended.
4.3.2. 3-Hydroxypropan-1-yl benzoate (6b)14. The reaction was
carried out as in the case of Section 4.3.1 using DFBA (110 mg,
0.55 mmol) and 5b (38 mg, 0.5 mmol) at 20 ꢀC for 3 h. The yield of
6b (82%) was determined by 1H NMR using 1,4-dimethoxybenzene
as an internal standard. Pure 6b was obtained by column chro-
matography (silica gel/hexane:EtOAc¼2:1); IR (neat) 3416, 2960,
1718, 1277 cmꢂ1
.
1H NMR
d
8.04 (d, J¼7.3 Hz, 2H), 7.59e7.55
(m, 1H), 7.45 (dd, J¼7.7, 7.7 Hz, 2H), 4.50 (t, J¼6.2 Hz, 2H), 3.78 (dt,
J¼6.0, 6.0 Hz, 2H), 2.05e1.99 (m, 2H), 1.93 (t, J¼5.6 Hz, 1H). 13C
NMR
d 167.00, 133.04, 130.01, 129.57 (2C), 128.37 (2C), 61.73, 59.10,
31.84.
4.2. Benzoylation of alcohols with DFBA
4.3.3. 3-Hydroxy-2,2-dimethylpropan-1-yl benzoate (6c)15. The re-
action was carried out as in the case of Section 4.3.1 using DFBA
(110 mg, 0.55 mmol) and 5c (52 mg, 0.5 mmol) at 20 ꢀC for
30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼3:1) gave 6c (98 mg) in 94% yield; IR (neat) 3438,
4.2.1. Decyl benzoate (2a)11. To a CH2Cl2 solution (3 mL) of DFBA
(199 mg, 1.0 mmol) was added at 0 ꢀC under N2 atmosphere 1a
(79 mg, 0.5 mmol), and the mixture was stirred at 0 ꢀC for 30 min.
Then, the mixture was poured into satd aq NaHCO3 (20 mL) and
extracted with diethyl ether (20 mLꢁ3). The combined organic
layer was dried over MgSO4 and concentrated under reduced
pressure. Purification by column chromatography (silica gel/hex-
ane/Et2O¼10:1) gave 2a (127 mg) in 97% yield; IR (neat) 2925, 1721,
2963, 1720, 1274 cmꢂ1. 1H NMR
d
8.04 (d, J¼8.3 Hz, 2H), 7.57 (dd,
J¼7.4, 7.4 Hz, 1H), 7.45 (dd, J¼6.9, 6.9 Hz, 2H), 4.18 (s, 2H), 3.40 (s,
2H), 1.01 (s, 6H). 13C NMR
d
167.07, 133.08, 129.91, 129.55 (2C),
128.37 (2C), 69.68, 68.08, 36.64, 21.51 (2C).
1274 cmꢂ1. 1H NMR
d
8.06e8.04 (m, 2H), 7.56 (dd, J¼7.5, 7.5 Hz, 1H),
7.44 (dd, J¼7.5, 7.5 Hz, 2H), 4.32 (t, J¼6.7 Hz, 2H), 1.80e1.73 (m, 2H),
4.3.4. {1-(Hydroxymethyl)cyclopropyl}methyl benzoate (6d). The
reaction was carried out as in the case of Section 4.3.1 using DFBA
(110 mg, 0.55 mmol) and 5d (51 mg, 0.5 mmol) at 20 ꢀC for 5 h. The
yield of 6d (70%) was determined by 1H NMR using 1,4-dime-
thoxybenzene as an internal standard. Pure 6d was obtained by
column chromatography (silica gel/hexane:EtOAc¼2:1); IR (neat)
1.48e1.27 (m, 14H), 0.88 (t, J¼6.7 Hz, 3H). 13C NMR
d 166.64, 132.73,
130.49, 129.49 (2C), 128.26 (2C), 65.10, 31.86, 29.50 (2C), 29.27,
29.26, 28.69, 26.02, 22.65, 14.09.
4.2.2. 4-tert-Butylphenyl benzoate (2b). The reaction was carried
out as in the case of Section 4.2.1 using DFBA (199 mg, 1.0 mmol)
and 1b (75 mg, 0.5 mmol) at 20 ꢀC for 3 h. Purification by column
chromatography (silica gel/hexane/Et2O¼10:1) gave 2b (93 mg) in
73% yield; white solid. Mp 78 ꢀC (lit.12 80e82 ꢀC). IR (KBr) 2963,
3423, 2950,1714,1274 cmꢂ1. 1H NMR
d 8.07e8.05 (m 2H), 7.60e7.56
(m, 1H), 7.48e7.44 (m, 2H), 4.33 (s, 2H), 3.53 (d, J¼5.9 Hz, 2H), 2.16
(t, J¼6.1 Hz, 1H), 0.69e0.59 (m, 4H). 13C NMR
d 167.10, 133.06,
130.01, 129.62 (2C), 128.37 (2C), 68.65, 66.62, 22.56, 8.93 (2C).
HRMS (ESI) calcd for C12H14O3Na (MþþNa) 229.08352, found
229.08335.
1734,1264 cmꢂ1. 1H NMR
d
8.20 (d, J¼6.9 Hz, 2H), 7.65e7.62 (m,1H),
7.51 (dd, J¼7.6, 7.6 Hz, 2H), 7.44 (d, J¼8.7 Hz, 2H), 7.13
(d, J¼8.7 Hz, 2H), 1.34 (s, 9H). 13C NMR
d 165.34, 148.68, 148.56,
133.49, 130.15 (2C), 129.68, 128.52 (2C), 126.39 (2C), 120.98 (2C),
34.49, 31.42 (3C).
4.3.5. (2S,3S)-Diethyl 2-benzoyloxy-3-hydroxybutandioate (6e). The
reaction was carried out as in the case of Section 4.3.1 using DFBA
(110 mg, 0.55 mmol) and 5e (103 mg, 0.5 mmol) at 40 ꢀC for
30 min. After the reaction, THF (3 mL) and 1 M HCl (3 mL)
were added and the mixture was stirred at 20 ꢀC overnight. Then,
the mixture was poured into satd aq NaHCO3 (20 mL) and
extracted with diethyl ether (20 mLꢁ3). The combined organic
layer was dried over MgSO4 and concentrated under reduced
pressure. Purification by column chromatography (silica gel/
hexane:EtOAc¼1:1) gave 6e (110 mg) in 71% yield; white solid. Mp
51e53 ꢀC (lit.16 56e59 ꢀC). IR (KBr) 3428, 2982, 1763, 1748, 1718,
4.2.3. Cyclododecyl benzoate (2c)13. The reaction was carried out as
in the case of Section 4.2.1 using DFBA (199 mg, 1.0 mmol) and 1c
(92 mg, 0.5 mmol) at 40 ꢀC for 30 min. Purification by column
chromatography (silica gel/hexane/Et2O¼10:1) gave 2c (135 mg) in
94% yield; white solid. Mp 38e40 ꢀC. IR (KBr) 2935,1713,1276 cmꢂ1
.
1H NMR
J¼7.9, 7.4 Hz, 2H), 5.29e5.23 (m, 1H), 1.87e1.79 (m, 2H), 1.69e1.61
(m, 2H), 1.45e1.33 (m, 18H). 13C NMR
166.19, 132.60, 130.89,
d
8.24 (d, J¼8.0 Hz, 2H), 7.53 (dd, J¼7.6, 7.1 Hz,1H), 7.42 (dd,
d
129.45 (2C), 128.20 (2C), 72.85, 29.05(2C), 24.13(2C), 23.91, 23.28
(2C), 23.09 (2C), 20.82 (2C).
1265, 1225 cmꢂ1
.
1H NMR
d
8.05e8.03 (m, 2H), 7.59 (dd, J¼7.4,
7.4 Hz, 1H), 7.45 (dd, J¼7.8, 7.8 Hz, 2H), 5.66 (d, J¼2.2 Hz, 1H), 4.86
(dd, J¼7.5, 2.4 Hz, 1H), 4.33e4.21 (m, 4H), 3.26 (d, J¼7.3 Hz, 1H),
1.31 (t, J¼7.0 Hz, 3H), 1.20 (t, J¼7.2 Hz, 3H). 13C NMR
4.3. mono-Benzoylation of diols
d
170.87, 166.49, 165.23, 133.63, 129.92 (2C), 128.70, 128.49 (2C),
4.3.1. 2-Hydroxyethyl benzoate (6a)14. To a CH2Cl2 solution (3 mL)
of DFBA (111 mg, 0.55 mmol) was added at room temperature
under N2 atmosphere 5a (31 mg, 0.5 mmol), and the mixture was
stirred at 20 ꢀC for 30 min. Then, the mixture was poured into satd
aq NaHCO3 (20 mL) and extracted with diethyl ether (20 mLꢁ3).
The combined organic layer was dried over MgSO4 and concen-
trated under reduced pressure. The yield of 6a was determined by
1H NMR using 1,4-dimethoxybenzene as an internal standard (84%)
73.43, 70.66, 62.65, 62.16, 14.06, 14.03.
4.3.6. (2R,3R)-3-Hydroxybutan-2-yl benzoate (6f)17. The reaction
was carried out as in the case of Section 4.3.1 using DFBA
(199 mg, 1.0 mmol) and 5f (45 mg, 0.5 mmol) at 40 ꢀC for
30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼2:1) gave 6f (88 mg) in 89% yield; IR (neat) 3443,
2980, 1714, 1276 cmꢂ1 1H NMR
. d 8.07e8.05 (m, 2H), 7.60e7.56

N. Wakita, S. Hara / Tetrahedron 66 (2010) 7939e7945
7943
(m, 1H), 7.46 (dd, J¼8.0, 8.0 Hz, 2H), 5.07e5.00 (m, 1H),
3.95e3.89 (m, 1H), 2.00 (br s, 1H), 1.36 (d, J¼6.3 Hz, 3H), 1.27 (d,
73.62, 73.44, 26.18e21.45 (10C). HRMS (ESI) calcd for
C
26H32O4Na (MþþNa) 431.21928, found 431.22011.
J¼6.3 Hz, 3H). 13C NMR
d 166.23, 133.04, 130.21, 129.56 (2C),
128.37 (2C), 75.42, 70.10, 19.00, 16.21.
4.3.13. (4S,5S)-Diethyl 2-(diethylamino)-2-phenyl-1,3-dioxolane-4,5-
dicarboxylate (8e). To a CH2Cl2 solution (3 mL) of DFBA (199 mg,
1.0 mmol) was added at 20 ꢀC under N2 atmosphere 5e (206 mg,
1.0 mmol), and the mixture was stirred for 10 min. Then, the
mixture was poured into satd aq NaHCO3 (20 mL) and extracted
with diethyl ether (20 mLꢁ3). The combined organic layer was
dried over MgSO4 and concentrated under reduced pressure.
Purification by column chromatography (silica gel/hexane/
Et2O¼2:1) gave 8e (112 mg) in 31% yield. To a THF solution (3 mL) of
8e (112 mg, 0.31 mmol) was added 1 M aq HCl (3 mL) and the
mixture was stirred at 20 ꢀC overnight. The mixture was poured
into satd aq NaHCO3 (20 mL) and extracted with diethyl ether
(20 mLꢁ3). The combined organic layer was dried over MgSO4 and
concentrated under reduced pressure. Purification by column
chromatography (silica gel/hexane:EtOAc¼1:1) gave 6e (54 mg) in
88% yield. Compound 8e; IR (neat) 2981, 1748, 1117 cmꢂ1. 1H NMR
4.3.7. 3-Hydroxy-2,3-dimethylbutan-2-yl
benzoate
(6g)18. The
reaction was carried out as in the case of Section 4.3.1 using
DFBA (199 mg, 1.0 mmol) and 5g (59 mg, 0.5 mmol) at 20 ꢀC for
1
h. Purification by column chromatography (silica gel/
hexane:EtOAc¼3:1) gave 6g (95 mg) in 86% yield; IR (neat) 3439,
2988, 1714, 1287 cmꢂ1 1H NMR
7.99 (d, J¼7.0 Hz, 2H), 7.55
(dd, J¼7.3, 7.3 Hz, 1H), 7.44 (dd, J¼7.8, 7.8 Hz, 2H), 3.78 (s, 1H), 1.64
(s, 6H), 1.31 (s, 6H). 13C NMR
166.48, 132.84, 131.15, 129.40 (2C),
.
d
d
128.28 (2C), 89.89, 74.73, 25.13(2C), 21.78 (2C).
4.3.8. cis-2-Hydroxycyclohexyl benzoate (6h)19. The reaction was
carried out as in the case of Section 4.3.1 using DFBA (199 mg,
1.0 mmol) and 5h (58 mg, 0.5 mmol) at 40 ꢀC for 30 min. Purifi-
cation by column chromatography (silica gel/hexane:EtOAc¼2:1)
gave 6h (101 mg) in 92% yield; IR (neat) 3469, 2939,
d
7.63e7.60 (m, 2H), 7.34e7.32 (m, 3H), 4.73 (d, J¼6.2 Hz, 1H), 4.59
1716, 1279 cmꢂ1. 1H NMR
d
8.06 (d, J¼7.0 Hz, 2H), 7.58 (dd, J¼7.3,
7.3 Hz, 1H), 7.46 (dd, J¼7.9, 7.9 Hz, 2H), 5.24e5.21 (m, 1H), 3.97 (br
s, 1H), 2.06e1.38 (m, 8H). 13C NMR
166.23, 133.06, 130.37, 129.60
(d, J¼6.2 Hz, 1H), 4.28 (q, J¼7.0 Hz, 2H), 4.08e3.91 (m, 2H), 2.77 (q,
J¼7.1 Hz, 4H), 1.31 (t, J¼7.2 Hz, 3H), 1.14 (t, J¼7.2 Hz, 3H), 0.99 (t,
d
J¼7.2 Hz, 6H). 13C NMR
d 169.26, 169.02, 139.02, 128.67, 127.71 (2C),
(2C), 128.41 (2C), 74.61, 69.64, 30.40, 27.37, 21.81, 21.52.
127.55 (2C), 123.48, 75.91, 75.13, 61.74, 61.49, 40.28 (2C), 14.08,
13.99 (2C), 13.90. HRMS (EI) calcd for C19H28O6N 366.19111, found
366.19214.
4.3.9. cis-2-Hydroxycyclopentyl benzoate (6i)19. The reaction was
carried out as in the case of Section 4.3.1 using DFBA (199 mg,
1.0 mmol) and 5i (51 mg, 0.5 mmol) at 40 ꢀC for 30 min. Purification
by column chromatography (silica gel/hexane:EtOAc¼2:1) gave 6i
(90 mg) in 87% yield; IR (neat) 3468, 2970,1715,1278 cmꢂ1. 1H NMR
4.3.14. 3-Hydroxybutyl benzoate (6l)22 and 4-hydroxybut-2-yl ben-
zoate (6l0)22. The reaction was carried out as in the case of Section
4.3.6 using DFBA (149 mg, 0.75 mmol) and 5l (45 mg, 0.5 mmol) at
0 ꢀC for 30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼1:1) gave a mixture of 6l and 6l0 (77 mg) in 79%
yield (inseparable). From 1H NMR spectra, 6l and 6l0 were found to
d
8.05 (d, J¼7.1 Hz, 2H), 7.58 (dd, J¼7.8, 7.8 Hz, 1H), 7.45 (dd, J¼7.7,
7.7 Hz, 2H), 5.26e5.22 (m, 1H), 4.34e4.30 (m, 1H), 2.17e1.60 (m,
6H). 13C NMR
166.39, 133.04, 130.07, 129.57 (2C), 128.34 (2C),
d
77.36, 73.30, 30.78, 28.12, 19.41.
be formed in 1:1 ratio. 1H NMR
d 8.06e8.03 (m, 2H), 7.59e7.55 (m,
1H), 7.47e7.43 (m, 2H), 5.43e5.34 (m, 0.5H, 6l0), 4.64e4.58 (m,
0.5H, 6l), 4.41e4.36 (m, 0.5H, 6l), 3.98e3.97 (m, 0.5H, 6l), 3.70e3.66
(m, 1H, 6l0), 2.53 (br s, 0.5H), 2.14 (br s, 1H), 1.99e1.80 (m, 2H), 1.38
(t, J¼0.7 Hz, 1.5H, 6l0), 1.25 (t, J¼0.8 Hz, 1.5H, 6l).
4.3.10. cis-2-Hydroxycyclododecyl benzoate (6j). The reaction was
carried out as in the case of Section 4.3.1 using DFBA (199 mg,
1.0 mmol) and 5j (100 mg, 0.5 mmol) at 40 ꢀC for 30 min. Purifi-
cation by column chromatography (silica gel/hexane:EtOAc¼2:1)
gave 6j (144 mg) in 95% yield; white solid. Mp 1ꢂ111 ꢀC (lit20
.
1H NMR
4.3.15. 4-Hydroxy-4-methylpentan-2-yl benzoate (6m)23. The re-
action was carried out as in the case of Section 4.3.1 using
DFBA (199 mg, 1.0 mmol) and 5l (59 mg, 0.5 mmol) at 20 ꢀC for
30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼2:1) gave 6m (92 mg) in 83% yield; IR (neat) 3480,
112.5e113.5 ꢀC). IR (KBr) 3523, 2926, 1700, 1276 cm
d
8.07e8.05 (m, 2H), 7.59e7.55 (m, 1H), 7.45 (dd, J¼7.8, 7.4 Hz, 2H),
5.32 (t, J¼6.0 Hz, 1H), 4.00 (d, J¼5.2 Hz, 1H), 1.88e1.36 (m, 20H). 13C
NMR d 166.70, 133.02, 130.25, 129.61 (2C), 128.36 (2C), 71.46, 71.42,
28.89e21.31 (10C).
2975, 1714, 1281 cmꢂ1 1H NMR
. d 8.06e8.02 (m, 2H), 7.59e7.39
(m, 3H), 5.48e5.37 (m, 1H), 2.07 (dd, J¼14.8, 8.7 Hz, 1H), 1.77 (dd,
4.3.11. 2-Hydroxyphenyl benzoate (6k). The reaction was carried
out as in the case of Section 4.3.1 using DFBA (199 mg, 1.0 mmol)
and 5k (55 mg, 0.5 mmol) at 40 ꢀC for 30 min. Purification by
column chromatography (silica gel/hexane:EtOAc¼3:1) gave 6k
(95 mg) in 89% yield; white solid: mp 130 ꢀC (lit.21 130 ꢀC). IR (KBr)
J¼14.9, 3.3 Hz, 1H), 1.39 (d, J¼6.3 Hz, 3H), 1.28 (s, 3H), 1.26 (s, 3H).
13C NMR
d 166.17, 132.94, 130.44, 129.46 (2C), 128.37 (2C), 70.00,
69.36, 49.02, 29.91, 29.68, 21.76.
4.3.16. Methyl 3,5-di-O-benzoyl-
b-D-ribofuranoside (10) and methyl
3411, 1715, 1273 cmꢂ1. 1H NMR
d
8.24e8.22 (m, 2H), 7.68 (dd, J¼7.5,
7.5 Hz, 1H), 7.54 (dd, J¼7.7, 7.7 Hz, 2H), 7.22e7.17 (m, 2H), 7.09e7.07
(m, 1H), 7.01e6.97 (m, 1H), 5.43 (s, 1H). 13C NMR
165.07, 147.25,
2,5-di-O-benzoly- -ribofuranoside (11). The reaction was carried
b-D
out as in the case of Section 4.3.6 using 2.0 equiv of DFBA (199 mg,
1.0 mmol) at 40 ꢀC for 30 min. The yields of 10 (34%) and 11 (38%)
were determined by 1H NMR using 1,4-dimethoxybenzene as an
internal standard, respectively. Pure 10 and 11 were obtained by
column chromatography (silica gel/CHCl3:acetone¼20:1); 1024; IR
d
138.77, 134.04, 130.38 (2C), 128.73, 128.71 (2C), 127.18, 122.50,
121.12, 118.06.
4.3.12. cis-1,2-Dibenzoyloxycyclododecane (7j). The reaction was
carried out as in the case of Section 4.3.6 using DFBA (199 mg,
1.0 mmol) and 6j (152 mg, 0.5 mmol) at 40 ꢀC for 30 min.
(neat) 3469, 2936, 1724,1273 cmꢂ1. 1H NMR
7.60 (dd, J¼7.6, 7.4 Hz, 1H), 7.54 (dd, J¼7.5, 7.4 Hz, 1H), 7.45
(dd, J¼7.8, 7.8 Hz, 2H), 7.38 (dd, J¼7.8, 7.7 Hz, 2H), 5.54 (dd, J¼6.3,
4.8 Hz, 1H), 4.98 (s, 1H), 4.67e4.46 (m, 4H), 3.38 (s, 3H). 13C NMR
d
8.04 (d, J¼7.9 Hz, 4H),
Purification
hexane:EtOAc¼5:1) gave 7j (205 mg) in 99% yield; IR (neat)
2935, 1715, 1259 cmꢂ1 1H NMR
by
column
chromatography
(silica
gel/
d
166.25, 165.71, 133.62, 133.09, 129.78 (2C), 129.71, 129.68 (2C),
.
d
8.01 (d, J¼7.7 Hz, 4H), 7.55
128.91, 128.52 (2C), 128.32 (2C), 108.48, 78.35, 74.71, 74.30, 64.95,
(dd, J¼7.6, 7.3 Hz, 2H), 7.42 (dd, J¼7.7, 7.6 Hz, 4H), 5.50 (t,
55.26. Compound 11; white solid. Mp 136 ꢀC (lit.24 132e133 ꢀC). IR
J¼6.3 Hz, 2H), 2.01e1.83 (m, 4H), 1.59e1.25 (m, 16H). 13C NMR
(KBr) 3409, 2943, 1723, 1274 cmꢂ1. 1H NMR
7.60 (dd, J¼7.6, 7.4 Hz, 1H), 7.54 (dd, J¼7.5, 7.4 Hz, 1H), 7.45 (dd,
d
8.04 (d, J¼7.9 Hz, 4H),
d
166.11 (2C), 132.86 (2C), 130.37 (2C), 129.60 (4C), 128.29 (4C),

7944
N. Wakita, S. Hara / Tetrahedron 66 (2010) 7939e7945
J¼7.8, 7.8 Hz, 2H), 7.38 (dd, J¼7.8, 7.7 Hz, 2H), 5.54 (dd, J¼6.3,
4.8 Hz, 1H), 4.98 (s, 1H), 4.67e4.46 (m, 4H), 3.38 (s, 3H). 13C NMR
126.72, 77.30, 73.33, 30.83, 28.13, 21.24, 19.45. HRMS (ESI) calcd for
C
13H16O3Na (MþþNa) 243.09917, found 243.09905.
d
166.48, 166.10, 133.53, 133.11, 129.81 (2C), 129.75, 129.68 (2C),
129.08, 128.46 (2C), 128.34 (2C), 105.94, 80.78, 77.09, 71.11, 64.56,
55.14.
4.3.21. cis-2-Hydroxycyclodocecyl formate (18). The reaction was
carried out as in the case of Section 4.3.1 using N-(difluoromethyl)
morpholine (75 mg, 0.55 mmol) and 5j (100 mg, 0.5 mmol) at 20 ꢀC
for 30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼2:1) gave 18 (93 mg) in 82% yield; IR (neat) 3379,
4.3.17. Methyl
(13) and methyl 2-benzoyl-4,6-O-benzylidene-
3-benzoyl-4,6-O-benzylidene-
b
-
-
D
-glucopyranoside
-glucopyranoside
b
D
2947, 1727, 1200 cmꢂ1. 1H NMR
d
8.14 (s, 1H), 5.21 (t, J¼6.1 Hz, 1H),
(14). The reaction was carried out as in the case of Section 4.3.6
using DFBA (120 mg, 0.6 mmol) and 12 (141 mg, 0.5 mmol) at
40 ꢀC for 30 min. Purification by column chromatography (silica
gel/hexane:EtOAc¼2:1) gave 13 (104 mg) in 54% yield and 14
(35 mg) in 18% yield, and 15 (15 mg) in 6% yield, respectively. 13;
white solid. Mp 180e182 ꢀC (lit.22 183e184 ꢀC). IR (KBr) 3423,
3.90e3.88 (m, 1H), 1.79e1.35 (m, 20H). 13C NMR
d
161.11, 75.51,
71.48, 29.02, 24.65, 24.51, 24.41, 23.65, 23.52, 21.78, 21.74 (2C),
21.15. HRMS (ESI) calcd for C13H24O3Na (MþþNa) 251.16177, found
251.16185.
2866, 1725, 1276, 1080 cmꢂ1. 1H NMR
d 8.10e8.08 (m, 2H), 7.57 (t,
4.3.22. (4-Hydroxy-4-methylpentan-2-yl) pivalate (19) and (4-hy-
droxy-2-methylpentan-2-yl) pivalate (20). The reaction was carried
out as in the case of Section 4.3.6 using N-(1,1-difluoro-2,2-dime-
thylpropyl)pyrrolidine (177 mg, 1.0 mmol) and 5m (59 mg,
0.5 mmol) at 20 ꢀC for 30 min. Purification by column chroma-
tography (silica gel/hexane:EtOAc¼3:1) gave 19 (72 mg) in 71%
yield and 20 (36 mg) in 18% yield, respectively. Compound 19; IR
J¼7.4 Hz, 1H), 7.46e7.41 (m, 4H), 7.32e7.30 (m, 3H), 5.55 (br
s, 1H), 5.48 (t, J¼9.4 Hz, 1H), 4.47 (d, J¼7.5 Hz, 1H), 4.42 (dd, J¼8.5,
4.9 Hz, 1H), 3.87e3.80 (m, 2H), 3.75e3.70 (m, 1H), 3.64e3.58 (m,
1H), 3.63 (s, 3H), 2.73 (d, J¼3 Hz, 1H). 13C NMR
d 166.63, 136.78,
133.27, 129.92 (2C), 129.55, 129.00, 128.34 (2C), 128.17
(2C), 126.04 (2C), 104.57, 101.41, 78.55, 74.36, 73.60, 68.63, 66.45,
57.68. Compound 14; white solid. Mp 201e203 ꢀC (lit.25
(neat) 3446, 2974, 1725, 1169 cmꢂ1
2.22 (br s, 1H), 1,90 (dd, J¼14.9, 9.0 Hz, 1H), 1.66 (dd, J¼14.9, 3.1 Hz,
1H), 1.25e1.22 (m, 6H), 1.19 (s, 9H). 13C NMR
178.11, 69.91, 68.56,
. d 5.17e5.10 (m, 1H),
1H NMR
202e203 ꢀC). IR (KBr) 3552, 2871, 1710, 1281, 1096 cmꢂ1 1H
.
d
NMR
d
8.09 (d, J¼7.1 Hz, 2H), 7.61e7.38 (m, 8H), 5.60 (s, 1H), 5.19
48.75, 38.55, 29.70, 29.52, 26.97 (3C), 21.46. HRMS (ESI) calcd for
(dd, J¼9.0, 8.0 Hz, 1H), 4.62 (d, J¼7.8 Hz, 1H), 4.42 (dd, J¼10.4,
3.2 Hz, 1H), 4.07 (dt, J¼3.2, 9.1 Hz, 1H), 3.86 (t, J¼10.2 Hz, 1H),
3.58e3.54 (m, 1H), 3.52 (s, 3H), 2.63 (d, J¼3.3 Hz, 1H). 13C NMR
C11H22O3Na 225.14612, found 225.14613. Compound 20; IR (neat)
3446, 2972,1724, 1136 cmꢂ1. 1H NMR
d
4.12e4.09 (m,1H), 2.20 (br s,
1H), 1.96 (dd, J¼14.9, 9.2 Hz, 1H), 1.75 (dd, J¼14.8, 2.2 Hz, 1H), 1.54
(s, 3H), 1.52 (s, 3H), 1.23e1.19 (m, 3H), 1.17 (s, 9H). 13C NMR
177.69,
d
165.91, 136.84, 133.32, 129.94 (2C), 129.56, 129.33, 128.40 (2C),
d
128.36 (2C), 126.25 (2C), 102.37, 101.91, 80.90, 74.66, 72.42, 68.61,
66.16, 57.26. Compound 15.25 1H NMR
d
7.97e7.94 (m, 4H),
82.28, 64.76, 50.05, 39.25, 27.14 (3C), 26.84, 25.64, 24.56. HRMS
(ESI) calcd for C11H22O3Na (MþþNa) 225.14612, found 225.14614.
7.54e7.31 (m, 10H), 5.79 (t, J¼9.5 Hz, 1H), 5.56 (s, 1H), 5.47 (dd,
J¼8.0, 9.6 Hz, 1H), 4.71 (d, J¼7.8 Hz, 1H), 4.45 (dd, J¼4.9, 10.4 Hz,
1H), 3.96e3.88 (m, 2H), 3.74e3.68 (m, 1H), 3.54 (s, 3H).
Acknowledgements
We are grateful to Mitsubishi Gas Chemical Company, INC. for
their donation of DFMBA.
4.3.18. cis-2-Hydroxycyclohexyl nicotinate (16). The reaction was
carried out as in the case of Section 4.3.1 using N-(difluoro(pyridin-
3-yl)methyl)-N,N-diethylamine (200 mg, 1.0 mmol) and 5h (58 mg,
0.5 mmol) at 40 ꢀC for 30 min. Purification by column chroma-
tography (silica gel/hexane:EtOAc¼2:1) gave 16 (97 mg) in 88%
Supplementary data
yield; IR (neat) 3393, 2939, 1720, 1288 cmꢂ1. 1H NMR
d 9.24 (s, 1H),
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2010.08.029.
8.78 (d, J¼4.7 Hz, 1H), 8.31 (dd, J¼8.0, 3.2 Hz, 1H), 7.40 (dd, J¼7.8,
4.9 Hz, 1H), 5.28e5.26 (m, 1H), 4.01 (s, 1H), 2.21e1.41 (m, 8H). 13C
NMR
d 164.78, 153.14, 150.61, 137.16, 126.38, 123.30, 75.21, 69.25,
References and notes
30.35, 27.36, 21.61, 21.57. HRMS (ESI) calcd for C12H15O3NNa
(MþþNa) 244.09441, found 244.09473.
1. Green, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 3rd ed.; John
Wiley & Sons: New York, NY, 1999.
2. (a) Kobayashi, S.; Yoneda, A.; Fukuhara, T.; Hara, S. Tetrahedron Lett. 2004, 45,
1287e1289; (b) Kobayashi, S.; Yoneda, A.; Fukuhara, T.; Hara, S. Tetrahedron
2004, 60, 6923e6930; (c) Yoneda, A.; Fukuhara, T.; Hara, S. Chem. Commun.
2005, 3589e3590; (d) Nomoto, T.; Fukuhara, T.; Hara, S. Synlett 2006,
1744e1746.
3. Fukuhara, T.; Hasegawa, C.; Hara, S. Synthesis 2007, 1528e1534.
4. As for the selective mono-benzoylation of diols, see: (a) Kim, S.; Chang, H.; Kim,
W. J. J. Org. Chem. 1985, 50, 1751e1752 and references are cited therein; (b)
Reginato, G.; Ricci, A.; Roelens, S.; Scapecchi, S. J. Org. Chem. 1990, 55,
5132e5139; (c) Oikawa, M.; Wada, A.; Okazaki, F.; Kusumoto, S. J. Org. Chem.
1996, 61, 4469e4471; (d) Roelens, S. J. Org. Chem. 1996, 61, 5257e5263; (e)
Caddick, S.; McCarroll, A. J.; Sandham, D. A. Tetrahedron 2001, 57, 6305e6310;
(f) Clarke, P. A. Tetrahedron Lett. 2002, 43, 4761e4763.
5. N,N-Dimethylbenzamide diethylacetal was previously used as benzolyation of
diols.6 However it is not suitable for a benzolyation reagent because it is un-
stable and difficult to store for a long time.7
6. Hanessian, S.; Moralioglu, E. Can. J. Chem. 1972, 50, 233e245.
7. Suwada, M.; Fukuhara, T.; Hara, S. J. Fluorine Chem. 2007, 128, 1121e1125.
8. In the reaction of N,N-dimethylbenzamide dimethylacetal with diols, the cyclic
amide acetals were isolated and they changed to mono-benzoylated products
by acid treatment.6
4.3.19. 3-Hydroxy-2,2-dimethylpropan-1-yl 3-methylbenzoate (17a).
The reaction was carried out as in the case of Section 4.3.6 using
DFMBA (213 mg, 1.0 mmol) and 5e (51 mg, 0.5 mmol) at 40 ꢀC for
30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼3:1) gave 17a (96 mg) in 87% yield; IR (neat) 3447,
2962, 1719, 1279 cmꢂ1. 1H NMR
d 7.85e7.83 (m, 2H), 7.40e7.32 (m,
2H), 4.18 (s, 2H), 3.38 (d, J¼5.2 Hz, 2H), 2.41 (s, 2H), 2.32 (br s, 1H),
1.02 (s, 6H). 13C NMR
d
167.26, 138.16, 133.84, 130.08, 129.83, 128.25,
126.69, 69.60, 68.07, 36.69, 21.51 (2C), 21.21. HRMS (ESI) calcd for
C13H18O3Na (MþþNa) 245.11482, found 245.11487.
4.3.20. cis-2-Hydroxycyclopentyl 3-methylbenzoate (17b). The re-
action was carried out as in the case of Section 4.3.6 using
DFMBA (213 mg, 1.0 mmol) and 5i (51 mg, 0.5 mmol) at 40 ꢀC for
30 min. Purification by column chromatography (silica gel/
hexane:EtOAc¼3:1) gave 17b (97 mg) in 87% yield; IR (neat) 3470,
9. From NMR spectra of the crude mixture, formation of 4-fluoro-4-methylbut-2-
yl benzoate and 4-methyl-4-buten-2-yl benzoate was observed (<3%).
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the references are cited therein; (b) Wang, G.; Ella-Menye, J.-R.; Martin, M. S.;
Yang, H.; Williams, K. Org. Lett. 2008, 10, 4203e4206.
2968, 1714, 1280 cmꢂ1. 1H NMR
d 7.86e7.84 (m, 2H), 7.40e7.32 (m,
2H), 5.25e5.21 (m, 1H), 4.33e4.29 (m, 1H), 2.41 (s, 3H), 2.13e1.62
(m, 6H). 13C NMR
d
166.57, 138.18, 133.85, 130.08, 129.97, 128.26,

N. Wakita, S. Hara / Tetrahedron 66 (2010) 7939e7945
7945
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