A new method for the synthesis of carboxylic esters and lactones with di-2-thienyl carbonate (2-DTC) by the promotion of DMAP and iodine

Article abstract of DOI:10.1246/bcsj.78.1508

The esterification of carboxylic acids with alcohols by using di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino) pyridine (DMAP) proceeded smoothly to afford the corresponding esters in good-to-high yields along with 2(5H)-thiophenone. This esterification was accelerated by the addition of an equimolar amount of iodine to afford the esters in higher yields within a shorter reaction time. Further, cyclization of ω-hydroxycarboxylic acids with an equimolar amount of 2-DTC in the presence of a catalytic amount of DMAP, followed by the addition of 1-4 equimolar amounts of iodine, afforded the corresponding lactones in good-to-high yields under mild conditions. This method was successfully employed in the synthesis of erythro-aleuritic acid lactone.

Full text of DOI:10.1246/bcsj.78.1508

1508 Bull. Chem. Soc. Jpn., 78, 1508–1519 (2005)
Ó 2005 The Chemical Society of Japan
A New Method for the Synthesis of Carboxylic Esters and Lactones with
Di-2-thienyl Carbonate (2-DTC) by the Promotion of DMAP and Iodine
ꢀ;1;2
Yoshiaki Oohashi,1 Kentarou Fukumoto,1 and Teruaki Mukaiyama
1The Kitasato Institute, Center for Basic Research, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
2Kitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
Received January 27, 2005; E-mail: mukaiyam@abeam.ocn.ne.jp
The esterification of carboxylic acids with alcohols by using di-2-thienyl carbonate (2-DTC) in the presence of a
catalytic amount of 4-(dimethylamino)pyridine (DMAP) proceeded smoothly to afford the corresponding esters in good-
to-high yields along with 2(5H)-thiophenone. This esterification was accelerated by the addition of an equimolar amount
of iodine to afford the esters in higher yields within a shorter reaction time. Further, cyclization of !-hydroxycarboxylic
acids with an equimolar amount of 2-DTC in the presence of a catalytic amount of DMAP, followed by the addition of
1–4 equimolar amounts of iodine, afforded the corresponding lactones in good-to-high yields under mild conditions. This
method was successfully employed in the synthesis of erythro-aleuritic acid lactone.
The preparation of carboxylic esters from nearly equimolar
amounts of carboxylic acids and alcohols is one of the most
Results and Discussion
important and fundamental methods in synthetic organic
chemistry. Therefore, several useful methods for those esteri-
fications have been developed,1–11 and are widely employed
in the synthesis of natural or unnatural molecules that have
carboxylic ester moieties. Since the development of useful
coupling reagents is still an important topic, to design and pre-
pare active esters that possess a new efficient leaving group is
an important problem in synthetic chemistry. Thus, carboxylic
acid ester 1, derived from a five-membered hetero lactone 2,
such as 2(5H)-thiophenone 2b, was chosen because it would
behave as a useful reagent that reacts effectively accompanied
by the transformation of 2-oxyheteroaryl moieties of 1 to more
stable lactone 2, which is inert and no longer involved in fur-
ther reactions (Scheme 1). Next, the synthetic strategy for the
preparation of active ester 1 from carboxylic acid was planned;
namely, the desired active ester 1 is derived from the corre-
sponding carbonate 3 formed by the reaction of a carboxylic
acid with a coupling reagent, such as 4 (Scheme 2).
Esterification of Carboxylic Acids with Alcohols by Us-
ing Di-2-thienyl Carbonate (2-DTC) via 2-Thienyl Active
Esters. In the first place, the reaction of various 2-heteroaryl
benzoates 5 with alcohols was tried in the presence of DMAP
to examine the reactivity of various active carboxylic esters
(Table 1). The desired esters were formed most effectively
in the case when 2-furyl benzoate 5a was used (Entries 1
and 2). The corresponding esters were obtained in good yields
upon a treatment of 2-thienyl benzoate 5b with alcohols for a
long time (Entries 3 and 4) while reactions of 2-(1-methylpyr-
roryl) benzoate 5c with alcohols proceeded sluggishly and
afforded the desired esters in lower yields (Entries 5 and 6).
Next, syntheses of the corresponding coupling reagents 4
were examined to use in the preparations of 2-furanyl ester
1a (X ¼ O) and 2-thienyl ester 1b (X ¼ S). The reaction
was carried out by using commercially available ꢀ-crotonolac-
tone or 2(5H)-thiophenone and triphosgene in the presence of
various bases, such as NEt3 and i-Pr2NEt in CH3CN (Table 2).
Di-2-thienyl carbonate (2-DTC) 4b was prepared in good yield
In this communication, we would like to report on di-2-
thienyl carbonate (2-DTC), a new and effective coupling re-
agent, for the esterification of carboxylic acids with alcohols,
and also the lactonization of !-hydroxycarboxylic acids in
the presence of a catalytic amount of DMAP and 1–4 equimo-
lar amounts of iodine under mild conditions.
O
O
3
O
R
O
O
X
R
O
1
X
O
O
4
O
H
O
R
O
O
O
NuH
X
X
H
+
R
Nu
O
X
4
R
O
X
low nucleophilicity
1
4a: (X = O)
4b: (X = S)
4c: (X = NMe)
1a: (X = O)
1b: (X = S)
2
1c: (X = NMe)
Scheme 2. Preparation of 1 from carboxylic acid by using
new coupling reagents 4.
Scheme 1. Esterification by using new active esters.
Published on the web August 4, 2005; DOI 10.1246/bcsj.78.1508

Y. Oohashi et al.
Bull. Chem. Soc. Jpn., 78, No. 8 (2005) 1509
Table 3. Synthesis of 2-Thienyl 3-Phenylpropionate
Table 1. Esterification of Various Active Esters 5a–c Pre-
pared from Benzoic Acid with Alcohols in the Presence
of DMAP
O
O
O
O
S
S
O
ROH
O
2-DTC (1.0 equiv.)
O
(1.0 equiv.)
R
OH
R
O
S
Base (10 mol%)
CH2Cl2, rt
6 (1.0 equiv.)
R = Ph(CH2)2
Ph
OR
Ph
O
X
7
DMAP (10 mol%)
CH2Cl2, rt
5
Entry
Base
none
DMAP
TEA
DBU
Time/h
Yield/%
Entry
5
X
ROH
Time/h
Yield ( )a)/%
1
2
3
4
5
6
5
10 (min)
N.D.
quant.
83
77
64
1
2
3
4
5
6
5a
5a
5b
5b
5c
5c
O
O
S
S
NMe
NMe
BnOH
PhOH
BnOH
PhOH
BnOH
PhOH
1
1.5
48
24
48
24
80
90
72 (6)
85 (15)
39 (46)
44 (56)
10
4
32
4
Pyridine
TMEDA
93
a) Yield of active esters 5.
Table 4. Synthesis of 3-Phenylpropyl 3-Phenylpropionate
Ph(CH2)3OH
(1.0 equiv.)
O
Table 2. Synthesis of Di-2-thienyl Carbonate (2-DTC) from
2(5H)-Thiophenone
O
R
O
Ph
R
O
S
Base (10 mol%)
CH2Cl2, rt
O
8
7 (1.0 equiv.)
R = Ph(CH2)2
Cl3C
CCl3
O
O
O
triphosgene
Entry
Base
none
Time/h
Yield/%
O
O
O
X
X
2
X
1
2
3
4
5
6
22
4
22
6
22
22
N.D.
93
23
76
N.D.
16
Base (equiv.)
CH3CN
4
DMAP
TEA
DBU
Pyridine
TMEDA
4b (X ¼ S)
4a (X ¼ O)
Entry
Base/equiv
Time
/h
Yield
/%
Time
/h
Yield
/%
1
2
3
4
TEA (1.05)
Pyridine (1.05)
DBU (1.05)
i-Pr2NEt2 (1.0)
2,6-di-tBu-
Pyridine (1.05)
Proton spongea)
(1.05)
6
6
6
4
29
N.D.
trace
73
24
24
24
24
N.D.
N.D.
N.D.
N.D.
Table 5. Effect of Solvent
Ph(CH2)3OH
(1.0 equiv.)
O
O
R
R
OH
O
Ph
5
6
4
4
N.D.
N.D.
2-DTC (1.0 equiv.)
DMAP (10 mol%)
solvent, rt
6 (1.0 equiv.)
8
R = Ph(CH2)2
Entry
Solvent
Time/h
Yield/%
a) 1,8-Bis(dimethylamino)naphthalene.
1
2
3
4
5
6
CH2Cl2
Et2O
THF
CH3CN
Toluene
DMF
6
9
24
9
24
48
94
92
87
84
89
38
upon a treatment of 2(5H)-thiophenone with triphosgene in the
presence of i-Pr2NEt (Entry 4); however, the desired di-2-furyl
carbonate 4a was not prepared in the case when ꢀ-crotonolac-
tone was used. It is noted that di-2-thienyl carbonate (2-DTC)
4b is a stable crystalline compound, and can be stored under
argon at room temperature for over one month without any de-
composition.
Alcohol was added to mixture of RCO2H and 2-DTC, DMAP
in solvent at 10 min latter.
Then, the preparation of 2-thienyl 3-phenylpropionate 7 by
using 3-phenylpropionic acid and 2-DTC in the presence of
various bases was examined (Table 3). The reaction completed
immediately to afford thienyl ester 7 in high yield along with
the evolution of carbon dioxide when DMAP was used as a
base (Entry 2). On the other hand, the reaction did not proceed
effectively in the cases of using other bases, such as NEt3 or
pyridine (Entries 3–6).
Next, the effect of bases on the synthesis of the ester from
thus-formed thienyl ester 7 and 3-phenyl-1-propanol was stud-
ied (Table 4). The corresponding ester 8 was not detected
when the acylation of 3-phenyl-1-propanol with 7 was tried
in the absence of bases (Entry 1). On the other hand, this reac-
tion proceeded most smoothly when DMAP was used (En-
try 2). These results indicate that a catalytic amount of DMAP
worked as a useful activator, and the acylpyridinium salts are
considered to be key intermediates in the above two steps.
The esterification of 3-phenylpropionic acid with 3-phenyl-
1-propanol was then tried by using 2-DTC. The reaction pro-
ceeded smoothly in the presence of a catalytic amount of
DMAP in CH2Cl2 to afford the corresponding ester in high
yield.12 The desired ester was similarly afforded in other sol-
vents, such as Et2O, CH3CN, and toluene (Table 5).
The experimental results obtained by using various carbox-
ylic acids and alcohols are listed in Table 6. The condensation

1510 Bull. Chem. Soc. Jpn., 78, No. 8 (2005)
2-DTC Mediated Esterification Reactions
Table 6. Esterification of Various Carboxylic Acids and Alcohols by Using 2-DTC
O
O
2-DTC (1.0 equiv.)
+
R'OH
DMAP (10 mol%)
CH2Cl2, rt
R
OH
R
OR'
(1.0 equiv.)
(1.0 equiv.)
Entry
RCO2H
R0OH
RCO2R0
Time/h
Yield/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
PhCH2CH2CO2H
PhCH2CH2CO2H
PhCH2CH2CO2H
PhCH2CH2CO2H
PhCH2CH2CO2H
c-C6H11CO2H
PhMeCHCO2H
PhMeCHCO2H
Ph2CHCO2H
Ph2CHCO2H
3-PyCH2CH2CO2H
PhCH2CH2CO2H
PhCH(OTBS)CH2CO2H
(E)-PhCH=CHCO2H
PhCO2H
Ph(CH2)3OH
BnOH
Ph(CH2)2CHCH3OH
c-C6H11OH
PhOH
Ph(CH2)3OH
Ph(CH2)3OH
c-C6H11OH
Ph(CH2)3OH
Ph(CH2)2CHCH3OH
Ph(CH2)3OH
THPO(CH2)5OH
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
8
9
6
4
8
11
2
11
4
94
96
82a)
81a)
95
10
11
12
13
14
15
16
17
18
19
20
21
22
23
87
95a)
92a)
95a)
86a)
84
8
11
22
6
9
93
85
37
33
21
22
22
22
Me3CCO2H
N.D.
a) 1.2 equiv of alcohol was used.
O
O
N
O
2-DTC
(1)
+
R
OH
R
O
S
O
+
S
2b
X
DMAP
−CO2
O
X
O
N
-
1b
O
O
O
+S
(fast)
R
O
S
O
R
O
(2)
R'
2b
1b
1b + R'OH
R
O
DMAP
I
(slow)
O
R'OH
O
+
+
O
Scheme 3. Esterification of carboxylic acids with alcohols
using 2-DTC in the presence of DMAP.
R'
N
H
O
X
S
R
O
Scheme 4. Acylation of 2-thienyl ester 1b with alcohol
using halogenating reagents.
of 3-phenylpropionic acid with various alcohols afforded the
corresponding esters in good-to-high yields (Entries 1–5).
The corresponding esters were also obtained in good yields
when ꢁ,ꢁ-disubstituted carboxylic acids and secondary alco-
hols were used (Entries 8 and 10). In the case when substrates
possessing a basic part or acid-sensitive moieties in the same
molecule were used, esters were also obtained in good-to-high
yields (Entries 11–13). On the other hand, this method had
some disadvantages because it needed a relatively long reac-
tion time, and failed to work well when cinnamic acid, aromat-
ic acid, or hindered carboxylic acid, such as pivalic acid, were
used (Entries 14–16). Therefore, it was desired to develop a
more effective method of 2-DTC-mediated esterification appli-
cable to a variety of carboxylic acids.
This reaction is considered to proceed via a two-step proce-
dure: i.e., i) the reaction of carboxylic acid with 2-DTC that
formed thienyl ester 1b and ii) the formation of an ester from
thus-formed 1b and various alcohols (Scheme 3). Since it was
the second step that controlled the reaction rate, it was as-
sumed that acceleration of the acylation step of alcohol with
thienyl ester 1b was essential. Then, the halogenation of thi-
enyl ester 1b was studied first because 2-oxythiophene moiety
of the thienyl ester 1b was thought to behave as a nucleophile
in the coexistence of oxidants, such as halogenating reagents.
Since thienyl ester 1b was halogenated readily by using suit-
able halogenating reagents, such as N-haloimides, to form an
active intermediate I, the reaction was expected to proceed
smoothly under mild conditions to afford esters (Scheme 4).
Based on this consideration, the esterification of thienyl esters
with alcohols by using several halogenating reagents was stud-
ied next.
Then, the reaction of 2-thienyl 3-phenylpropionate 7 (R ¼
Ph(CH2)2) with 3-phenyl-1-propanol was tried by using vari-
ous halogenating reagents (Table 7). When N-haloimides, such
as N-bromosuccinimide, N-iodosuccinimide, N-chlorosuccin-
imide, and N-bromophthalimide, were used (Entries 3–6), the
desired esters were always obtained in low yields, and mostly
5-halogenated 2-thienyl 3-phenylpropionate 24 was afforded.
In the case of using copper(I) iodide, the desired ester was
not detected, although it was thought that the affinity of copper
to sulfur would promote this reaction (Entry 7). On the other

Y. Oohashi et al.
Bull. Chem. Soc. Jpn., 78, No. 8 (2005) 1511
Table 7. Effect of Halogenating Reagents
O
O
O
R'OH (1.2 equiv.)
+
X
(X=Cl, Br, I)
R
O
R
OR'
S
Activator
(1.0 equiv.)
R
O
S
(1.0 equiv.)
24
CH2Cl2, rt
Yield/%
Entry
R
R0
Activator
Time/h
Ester
24
1
2
3
4
5
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
PhCH2CH2
Ph
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Ph(CH2)3
Bn
none
DMAPa)
NBS
NIS
NCS
NBPb)
CuI
I2
Br2
I2
Br2
22
4
2
48
48
4
22
1
N.D.
93
23c)
40c)
22c)
36
N.D.
83
94
76
N.D.
N.D.
59
35
39
6
52
7d)
8
N.D.
N.D.
N.D.
N.D.
36
9
10
11
2
2.5
3
Ph
Bn
28
a) 10 mol % of DMAP was used. b) N-bromophthalimide. c) 1.0 equiv of alcohol was used.
d) CH3CN was used as a solvent.
tries 5 and 6). Further, it is noteworthy that even when the
amount of DMAP was reduced to 1=2, the formation of thienyl
ester 1b of the first step proceeded smoothly in CH3CN while
the reaction of forming 1b proceeded more sluggishly in
CH2Cl2 (Entries 7 and 8).
Table 8. Esterification of 3-Phenylpropionic Acid with 3-
Phenyl-1-propanol in the Presence of DMAP and Iodine
2-DTC
(1.0 equiv.)
DMAP
(mol%)
R'OH
(1.2 equiv.)
O
O
The results of esterifications using various carboxylic acids
and alcohols by the above-mentioned method of using only a
catalytic amount of DMAP (method A)12 or a method of the
combined use of a catalytic amount of DMAP and an equimo-
lar amount of iodine (method B)13 are listed in Table 9. The
esterification of 3-phenylpropionic acid with various alcohols
proceeded smoothly to afford the corresponding esters in
good-to-high yields when nearly equimolar amounts of pri-
mary or secondary alcohols were used (method B, Entries 1–
4). Also, esters were obtained in good-to-high yields in the
case when ꢁ,ꢁ-disubstituted carboxylic acids were used
(method B, Entries 5–7). A hindered carboxylic acid, such as
pivalic acid, also afforded the desired esters rapidly in good-
to-high yields, whereas the corresponding ester was not afford-
ed at all in the absence of iodine (method A, Entry 8). It is in-
teresting to note that these reactions completed rapidly in the
presence of iodine i.e. 30 min–1 h (method B, Entries 1–9).
On the other hand, it took a much longer time i.e. 2–48 h in
the absence of iodine (method A, Entries 1–8). Similarly, the
corresponding esters were also obtained rapidly in good-to-
high yields when trans-cinnamic acid as well as crotonic acid
and aromatic acids were used (method B, Entries 14–17, 20,
and 21), whereas these acids gave the corresponding esters
in low yields when the reactions were carried out under the
conditions of method A (Entries 14–16, 20, and 21). It is note-
worthy that the corresponding esters were obtained in good-to-
high yields when substrates containing active olefinic moieties,
such as trans-hexenoic acid or trans-styrylacetic acid, were
used in the presence of iodine (method B, Entries 18 and
19). However, it needed a relatively long reaction time, and
failed to work well when aliphatic acids having an aryl group
on the ꢁ-position of carbonyl or aromatic acids having elec-
R
OH
R
OR'
I2 (equiv.)
Solvent,
(1.0 equiv.)
rt, 10min.
R' = Ph(CH2)3
R = Ph(CH2)2
DMAP
/mol %
Entry
I2/equiv
Solvent
Time/h Yield/%
1
2
3
4
5
6
7
8
10
10
10
10
10
10
5
none
CH2Cl2
Et2O
THF
Toluene
CH2Cl2
CH3CN
6
2
2
1
0.5
0.5
1.5
0.5
94
94
71
82
91
91
92a)
94
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.1)
I2 (1.05) CH2Cl2
I2 (1.05) CH3CN
5
a) Reaction time for the formation of 2-thienyl ester, active
ester, became longer (1 h).
hand, the desired ester was obtained in good-to-high yields
when iodine or bromine was used as an activator (Entries 8
and 9). Then, the esterification of 2-thienyl benzoate 5b
(R ¼ Ph) with benzyl alcohol was further examined by using
iodine or bromine as an activator, and the corresponding ester
was obtained in a good yield when iodine was used (Entry 10).
In the case of using bromine, however, the yield was low and
5-bromo-2-thienyl benzoate was formed as a main product
(Entry 11). These results clearly indicated that iodine is effec-
tive for promoting of the present esterification.
The esterification of carboxylic acids with alcohols was then
tried by using 2-DTC (Table 8). The reaction proceeded rapid-
ly when an equimolar amount of iodine was added in the pres-
ence of a catalytic amount of DMAP in CH2Cl2 or CH3CN,
and the corresponding esters were obtained in high yields (En-

1512 Bull. Chem. Soc. Jpn., 78, No. 8 (2005)
2-DTC Mediated Esterification Reactions
Table 9. Esterification of Various Carboxylic Acids with Alcohols Using 2-DTC Promoted by DMAP and Iodine (Methods A
and B)
O
O
2-DTC (1.0 equiv.)
R'OH (1.2 equiv.)
R
OH
R
OR'
I
2 (1.05 equiv.)
DMAP (5 mol%)
CH3CN, rt
(1.0 equiv.)
Method B
Method A
Entry
RCO2H
R0OH
RCO2R0
Time/h
Yield/%
Time/h
Yield/%
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
PhCH2CH2COOH
PhCH2CH2COOH
PhCH2CH2COOH
PhCH2CH2COOH
c-C6H11COOH
c-C6H11COOH
c-C6H11COOH
Me3CCOOH
Me3CCOOH
Ph(CH2)3OH
8
10
11
12
13
25
26
23
27
14
15
16
17
21
28
29
30
31
32
22
33
34
35
36
0.5
0.5
1
0.5
0.5
0.5
0.5
0.5
0.5
2
2
6
6
0.5
0.5
0.5
0.5
2
94
90
88
84
6
8
11
2
11
48
42
22
94a)
82
Ph(CH2)2CH(OH)CH3
c-C6H11OH
PhOH
Ph(CH2)3OH
Ph(CH2)2CH(OH)CH3
c-C6H11OH
Ph(CH2)3OH
Ph(CH2)2CH(OH)CH3
Ph(CH2)3OH
c-C6H11OH
Ph(CH2)3OH
Ph(CH2)2CH(OH)CH3
Ph(CH2)3OH
Ph(CH2)2CH(OH)CH3
Ph(CH2)3OH
Ph(CH2)2CH(OH)CH3
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
PhOH
81
95a)
87a)
69
91
93b)
89
86
N.D.
91
81
PhMeCHCOOH
PhMeCHCOOH
Ph2CHCOOH
93b)
81c)
51c)
52c)
88
4
8
95
92
95
86
37
22
<8
11
22
22
22
22
Ph2CHCOOH
(E)-PhCH=CHCOOH
(E)-PhCH=CHCOOH
(E)-CH3CH=CHCOOH
(E)-CH3CH=CHCOOH
(E)-PhCH=CHCH2COOH
(E)-EtCH=CHCH2COOH
PhCOOH
p-MeOPhCOOH
p-ClPhCOOH
p-CF3PhCOOH
83
84
82
85d)
80d)
89
87
68
1
6
0.5
4
24
24
22
22
14
12
14
33a)
3a)
94
91
90
PhOH
PhOH
32
25
p-NO2PhCOOH
Method A: To a mixture of carboxylic acids (1.0 equiv) and 2-DTC (1.0 equiv) in CH2Cl2 was added DMAP (10 mol %).
After stirring for 10 minutes at room temperature, alcohols (1.2 equiv) was added and the mixture was stirred at room tem-
perature. Method B: To a mixture of carboxylic acids (1.0 equiv) and 2-DTC (1.0 equiv) in CH3CN was added DMAP (5
mol %). After stirring for 10 minutes at room temperature, alcohols (1.2 equiv) was added and then iodine (1.05 equiv) was
added. The reaction mixture was stirred at room temperature. a) 1.0 equiv of alcohol was used. b) Reactions were performed
by using 10 mol % of DMAP, and 1.1 equiv of iodine, and CH2Cl2 as a solvent. c) Reactions were performed by using 10
mol % of DMAP, and 1.5 equiv of iodine, and CH2Cl2 as a solvent. d) Toluene was used as a solvent.
tron-withdrawing groups were used (method B, Entries 10–13
and 22–24). On the other hand, these acids gave the corre-
sponding esters in high yields under the conditions of meth-
Table 10. Esterification of 2-Thienyl 3-Phenylpropionate in
the Presence of a Catalytic Amount of Iodine
Ph(CH2)3OH
(1.0 equiv.)
od A (Entries 10–13 and 22–24). These results indicate that
the desired esters were obtained in high yields by a suitable
choice of one of these two methods (method A and B) accord-
ing to the nature of the substrates.
O
O
R
O
R
O
Ph
S
I2 (mol%)
Solvent, rt
7 (1.0 equiv.)
R = Ph(CH2)2
8
In order to improve the utility of 2-DTC mediated esterifica-
tion, the above reaction was tried by using catalytic amounts of
DMAP and iodine. Then, the acylation of 3-phenyl-1-propanol
with 2-thienyl ester 7 in the presence of a catalytic amount of
iodine was examined (Table 10). The reaction proceeded ef-
fectively to afford the corresponding ester in high yield when
10 mol % of iodine was used in CH3CN (Entry 6), whereas the
reaction was very slow in CH2Cl2 (Entry 2). The above results
indicate that a catalytic amount of iodine worked effectively in
the second step that afforded esters.
Entry
I2/mol %
Solvent
Time/h
Yield/%
1
2
3
4
5
6
100
20
100
30
CH2Cl2
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
2.5
24
83
71
93
87
95
90
0.5
0.5
0.5
1
20
10
Next, the esterification of various carboxylic acids with al-
cohols was tried by using 2-DTC in the presence of a catalytic
amount of DMAP and iodine in CH3CN (Table 11). The reac-
tion proceeded smoothly to afford the corresponding esters in
good-to-high yields, except when cyclohexanol or pivalic acid
was used (Entries 4 and 7).

Y. Oohashi et al.
Bull. Chem. Soc. Jpn., 78, No. 8 (2005) 1513
Table 11. Esterification of Various Carboxylic Acids and Alcohols in the Presence of Catalytic
Amounts of DMAP and Iodine
O
O
2-DTC (1.0 equiv.) R'OH (1.2 equiv.)
R
OR'
R
OH
DMAP (2 mol%)
CH3CN, rt
I2 (32 mol%)
(1.0 equiv.)
Entry
RCO2H
R0OH
Time/h
Yield/%
1
2
3
4
5
6
7
8
9
10
PhCH2CH2COOH
PhCH2CH2COOH
PhCH2CH2COOH
PhCH2CH2COOH
c-C6H11COOH
c-C6H11COOH
Me3CCOOH
PhCH=CHCOOH
CH3CH=CHCOOH
p-MeOPhCOOH
Ph(CH2)3OH
BnOH
Ph(CH2)2CH(OH)CH3
c-C6H11COOH
Ph(CH2)3OH
Ph(CH2)2CH(OH)CH3
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
Ph(CH2)3OH
2
0.5
2
3.5
0.5
0.5
2
0.5
1.5
2
90
91
80
58a)
84
81
57b)
81
74
86
a) 2 mol % of DMAP and 52 mol % of iodine were used. b) 5 mol % of DMAP and 35 mol % of
iodine were used.
Lactonization of !-Hydroxycarboxylic Acids by Using
Di-2-thienyl Carbonate (2-DTC) via 2-Thienyl Active
Esters. Natural products having a macrolide structure are im-
portant therapeutic agents in clinical medicine because of their
antibiotic, antitumoral, and other various helpful biochemical
activities. Accordingly, to prepare macrolactones from !-hy-
droxycarboxylic acids is also a major concern in synthetic or-
ganic chemistry. Several useful methods have therefore been
reported: namely, the use of N,N-dicyclohexylcarbodiimide
(DCC),1 2,4,6-trichlorobenzoyl chloride,2 2,20-dipyridyl disul-
fide/Ph3P,3 1-methyl-2-chloropyridinium iodide/Et3N,4 dieth-
yl azodicarboxylate (DEAD)/Ph3P,5 2-methyl-6-nitrobenzoic
anhydride (MNBA),8 4-(trifluoromethyl)benzoic anhydride,9
4-nitrobenzoic anhydride/Sc(OTf)3,10 etc.
In the previous section, a new esterification method between
nearly equimolar amounts of carboxylic acids and alcohols by
using 2-DTC in the presence of a catalytic amount of DMAP is
described. In addition, it was found that this esterification was
accelerated by further addition of an equimolar amount of io-
dine, which improved the reaction time and yield. This result
prompted us to study the 2-DTC-mediated macrolactonization
of !-hydroxycarboxylic acids in the coexistence of iodine.14
In the first place, the synthesis of 2-thienyl 12-hydroxydo-
decanoate 38, an active ester intermediate, was examined by
treating 12-hydroxydodecanoic acid 37 with 2-DTC in the
presence of a catalytic amount of DMAP (Table 12). The for-
mation of 38 was considerably influenced by solvents, and was
obtained most effectively when the reaction was carried out in
CH3CN (Entry 5), and also when the amount of DMAP was
reduced to 5 mol % (Entry 6). It is interesting to note that
the corresponding lactone was not detected when it was al-
lowed to react under more concentrated conditions (35 mM)
for 9 h (Entry 7). This indicates that the lactonization is not
accelerated by DMAP alone; therefore, it needed to use the
second activator so as to form a lactone efficiently.
Table 12. Synthesis of 2-Thienyl 12-Hydroxy Dodecanoate
38 Using 12-Hydroxydodecanoic Acid 37 and 2-DTC in
the Presence of DMAP
O
O
2-DTC (1.0 equiv.)
DMAP (mol%)
HO
O
10
S
HO
OH
10
37
Solv. (18 mM) , rt
38
Entry
Solvent
DMAP/mol %
Time/min
Yield/%
1
2
3
4
5
6
7
CH2Cl2
Toluene
THF
10
10
10
10
10
5
60
90
120
120
15
81
73
59
49
97
95
96a)
Et2O
CH3CN
CH3CN
CH3CN
15
9 h
5
a) Concentration 35 mM.
38, as described above. However, the corresponding lactone
was obtained in low yield when a solution of 12-hydroxydo-
decanoic acid, 2-DTC, and DMAP in CH3CN was diluted to
2 mM by further addition of CH3CN and iodine at room tem-
perature (Entry 1).
Thus, thienyl ester 38 was successfully prepared in CH3CN,
and the effect of the further addition of other solvents to the
above solution in the lactonization step under diluted condition
was examined next. After screening several solvents, it was
show that the desired lactone was obtained in 47% yield in a
2 mM solution by further addition of toluene (Entry 6).
It is also noted that the corresponding lactone was not de-
tected when the above reaction was carried out in the presence
of DMAP (2.05 equiv) instead of iodine (Entry 7). This result
indicates that iodine works quite effectively in this lactoniza-
tion step.
Next, the lactonization of 12-hydroxydodecanoic acid
which uses 2-DTC in the presence of DMAP and iodine,
was examined (Table 13). Acetonitrile then turned out to be
the most suitable solvent for the preparation of thienyl ester
With these results in mind, the amounts of iodine and sol-
vents were further examined in order to optimize the reaction
conditions (Table 14). Finally, it was found that the desired 12-
dodecanolide was obtained in 77% yield in the case when the

1514 Bull. Chem. Soc. Jpn., 78, No. 8 (2005)
2-DTC Mediated Esterification Reactions
Table 13. Lactonization of 12-Hydroxydodecanoic Acid 37
by Using 2-DTC Promoted by DMAP and Iodine
Table 15. Lactonization of Various !-Hydroxy Carboxylic
Acids by Using 2-DTC Promoted by DMAP and Iodine
O
O
O
O
10
n
I2
2-DTC
O
2-DTC
(1.0 equiv.)
O
lactone
+
lactone
I2 ( equiv.)
(1.0 equiv.)
(2.0 equiv.)
+
HO
OH
HO
OH
DMAP
(5 mol%)
toluene
reflux
10 h
O
10
DMAP
(5 mol%)
CH3CN, rt
Solv.
n
O
O
O
O
n
37
10
n
(1.0 equiv.)
(1.0 equiv.)
CH3CN, rt
15 min.
10
O
15 min.
O
O
diolide
diolide
Solvent
(2 mM)a)
Yieldb)/%
Yielda)/% (ring size)
Entry
Time/h
Entry
n
I2/equiv
Lactone
Diolide
Lactone
Diolide
1
2
CH3CN
CH3NO2
Et2O
24
24
8
8
8
28
25
N.D.
N.D.
<26
47
8.6
3
N.D.
trace
11
1
2
3
4
5
6
9
10
11
12
13
14
4
4
4
4
2
2
58 (12)
77 (13)
85 (14)
87 (15)
90 (16)
92 (17)
18
14
<8
<11
<6
<7
3c)
4c)
5c)
6c)
7c),d)
THF
CH2Cl2
toluene
toluene
8
8
22
N.D.
N.D.
a) Isolated yield.
A solution of 37 with 2-DTC in CH3CN (10 mL) was added
DMAP and diluted with solvent (78 mL), followed by addition
of iodine at room temperature. a) Values in parentheses was
the concentration without consideration of a change of total
volume owing to mix plural solvents. b) Isolated yield. c) re-
flux. d) Reaction was carried by using 2 equivalents of DMAP
instead of iodine.
Table 16. Lactonization of the Protected erythro-Aleuritic
Acid by Using 2-DTC Promoted by DMAP and Iodine
2-DTC
(1.0 equiv.)
HO
O
I2 ( equiv.)
DMAP
(5 mol%)
CH3CN, rt,
toluene
(1 mM)
reflux
OH
Table 14. Lactonization of 12-Hydroxydodecanoic Acid 37
by Using 2-DTC Promoted by DMAP and Iodine in
CH3CN–Toluene
O
O
15 min.
O
Ph
O
O
39 (1.0 equiv.)
2-DTC
(1.0 equiv.)
O
O
I2 ( equiv.)
10
HO
OH
DMAP
(5 mol%)
CH3CN, rt, 15 min.
10
toluene
reflux
lactone
37
+
O
Ph
Time/h
(1.0 equiv.)
diolide
O
40
I2
Conc.
/mMa)
Yieldb)/%
Entry
Time/h
I2
Yielda)/%
/equiv
Lactone
Diolide
Entry
/equiv
40
Diolide
1
2
3
4
5
6
0.5
1
2
1
2
2
2
2
1
1
1
20
8
8
8
8
40
50
47
57
67
77
21
19
19
16
15
14
1
2
3
2
1
0.2
3
4
20
85
85
65
5
<9
9
A solution of 39 with 2-DTC in CH3CN (10 mL) was added
DMAP and diluted with toluene (166 mL), followed by addi-
tion of iodine at room temperature. a) Isolated yield.
4
8
A solution of 37 with 2-DTC in CH3CN (10 mL) was added
DMAP and diluted with toluene (2 mM; 78 mL, 1 mM; 166
mL), followed by addition of iodine at room temperature. a)
The concentration without consideration of a change of total
volume owing to mix plural solvents. b) Isolated yield.
were obtained in high yields when the cyclization was
carried out using the corresponding !-hydroxycarboxylic
acids (Entries 3–6).
Further, the application of this 2-DTC mediated lactoniza-
tion method to the synthesis of functionalized macrocyclic
molecule was tried; that is, the lactonization of seco acid 39
derived from erythro-aleuritic acid by using 2-DTC in the
presence of DMAP and iodine was examined (Table 16). It
is interesting to note that the reaction proceeded smoothly
within 3 h under the above reaction conditions to afford the de-
sired lactone 40 in high yield without damaging the acid-sen-
sitive benzylidene protective group (Entry 1). The lactone 40
was also obtained in 85% and 65% yields, respectively, when
reaction was carried out in a 1 mM solution of toluene in the
presence of 4 equimolar amounts of iodine (Entry 6).12
The results concerning the lactonization of various !-hy-
droxycarboxylic acids are listed in Table 15. The correspond-
ing macrolactones were obtained in good-to-high yields along
with a small amount of diolide under the reaction conditions
mentioned above. The desired product was also obtained in
58% yield when 11-hydroxyundecanoic acid was used (En-
try 1). Fourteen to seventeen-membered ring macrolactones

Y. Oohashi et al.
Bull. Chem. Soc. Jpn., 78, No. 8 (2005) 1515
an equimolar amount of iodine (Entry 2) or a catalytic amount
of iodine (20 mol %) was used (Entry 3).
carboxylic acid with 2-DTC in the presence of DMAP (5
mol %) in CH3CN. However, no product was formed when
an equimolar amount of iodine was used instead of DMAP un-
der the above conditions. Step 2; the corresponding ester was
obtained by the acylation of alcohol with isolated thienyl ester
1b in the presence of 10 mol % of DMAP within 4 h. It is noted
that the above reaction proceeded faster (<1 h) in the presence
of 10 mol % of iodine to afford the ester in higher yield. These
results are explained by considering that a catalytic amount of
DMAP behaved effectively in the first step and iodine worked
efficiently in the second step.
The reported results8 concerning the synthesis of lactone 40
by using a mixed anhydride, namely, well-known Yamaguchi
and the MNBA methods, are listed in Table 17 to compare
with that obtained by the present new 2-DTC method.12 It is
noteworthy that the 2-DTC method gave the desired lactone
40 in high yield within a shorter time without employing a
slow addition procedure (Entry 1), whereas the above-men-
tioned mixed anhydride methods needed a long reaction time
under the slow addition conditions (Entries 2 and 3).
Mechanism for the Esterification of Carboxylic Acids
with Alcohols by Using 2-DTC Promoted by DMAP and
Iodine. The above procedure consists of two reactions.
Step 1; thienyl ester 1b was formed immediately by treating
In order to study the mechanism of this reaction, several 2-
thienyl esters were treated with alcohols in the presence of an
equimolar amount of iodine in d3-CD3CN (Scheme 5). The re-
action sequence was followed by measuring 1H NMR of the re-
action mixture to observe the formation of the corresponding
esters along with 2(5H)-thiophenone 2b, but not the assumed
5-iodo-2(5H)-thiophenone 41. This is explained by consider-
ing an initial formation of the active intermediate II instead
of the expected active intermediate III, and II reacts with
alcohols to afford the desired esters along with 2(5H)-thio-
phenone (Scheme 6).
The detailed mechanism concerning the esterification of
carboxylic acids with alcohols by using 2-DTC in the presence
of DMAP and iodine is shown in Scheme 7. The reaction of 2-
DTC 4b with DMAP formed acylpyridinium salt 42, which re-
acted with carboxylic acid to give 2-thienyl carbonate 3b and
2(5H)-thiophenone 2b. This carbonate 3b reacted with DMAP
to afford the acylpyridinium salt 43 along with the evolution of
carbon dioxide. The salt was then converted to 2-thienyl active
ester intermediate 1b along with the regeneration of DMAP
(cycle A). The thus-formed 1b was activated by iodine to gen-
erate an intermediate II, which in turn reacted with alcohol to
afford intermediate 44. The subsequent capture of a proton
from alcohol by the 2-thienyl part of 44 afforded the desired
ester along with 2b, and iodine was regenerated (cycle B).
Table 17. Lactonization of the Protected erythro-Aleuritic
Acid by Using Other Useful Reagents
O
HO
O
O
reagents
OH
O
O
O
O
Ph
Ph
39 (1.0 equiv.)
40
Reagents
/equiv
Yield/%
Entry
1a)
Time/h
3
40
Diolide
2-DTC (1.0 equiv)
/DMAP (5 mol %)
/I2 (2.0 equiv)
2,4,6-Trichlorobenzoyl
chloride (1.0 equiv)
/Et3N (1.1 equiv)
/DMAP (6.0 equiv)
MNBA (1.2 equiv)
/DMAP (2.4 equiv)
85
5
2b)
9
70
9
3c)
16
90
2
O
a) A solution of 39 (0.177 mmol) with 2-DTC in CH3CN (10
mL) was added DMAP and diluted with toluene (166 mL),
followed by addition of iodine at room temperature and then
stirred at reflux temperature. b) A solution of MA derived
from 39 (0.360 mmol) and 2,4,6-trichlorobenzoyl chloride in
toluene (36 mL) was slowly added to solution of DMAP in tol-
uene (180 mL) at reflux temperature. c) A solution of 39
(0.380 mmol) in CH2Cl2 (84.6 mL) was slowly added to solu-
tion of reagents in CH2Cl2 (135.8 mL) at rt.
R'OH (1.0 equiv.)
R
OR'
O
I2 (1.0 equiv.)
+
R
O
S
d3-CD3CN, rt
O
S
2b
1b
Scheme 5. NMR study of the reaction of 2-thienyl ester with
alcohol in the presence of iodine in d3-CD3CN.
O
O
R'OH
+ I2
+
R
OR'
O
O
R
O
S
I
S
+ I2
I
R
O
S
2b
II
1b
O
O
R'OH
+ HI
+
O
R
OR'
I
S
R
O
S
+
I
I-
41
III
Scheme 6. The active intermediate II derived from 2-thienyl ester 1b and iodine.

1516 Bull. Chem. Soc. Jpn., 78, No. 8 (2005)
2-DTC Mediated Esterification Reactions
1H NMR spectra were recorded on a JEOL JNM EX270L (270
MHz) spectrometer; chemical shifts (ꢂ) are reported in parts per
million relative to tetramethylsilane. The splitting patterns are
designated as s, singlet; d, doublet; t, triplet; q, quartet; m, multip-
let; br, broad. 13C NMR spectra were recorded on an EX270L (68
MHz) spectrometer with complete proton decoupling. The chemi-
cal shifts are reported in parts per million relative to tetramethyl-
silane with the solvent resonance as the internal standard (CDCl3;
ꢂ ¼ 77:0 ppm, C6D6; ꢂ ¼ 128:0 ppm). Mass spectra (MS) were
recorded on a JEOL JMS-SX102A, or SSQ7000 thermoelectron.
High-resolution mass spectra (HRMS) were recorded on a Q-
Tof ultima global micromass. Analytical TLC was performed on
Merck preparative TLC plates (silica gel 60 GF254, 0.25 mm).
Column chromatography was carried out on Merck silica gel
60 (0.063–0.200 mm). Preparative thin-layer chromatography
(PTLC) was carried out on silica-gel Wakogel B-5F. Reactions
in anhydrous dichloromethane, acetonitrile, or toluene were car-
ried out under an argon atmosphere in dried glassware. Dichloro-
methane was distilled from diphosphorus pentaoxide, then calci-
um hydride, and dried over MS 4A. Acetonitrile and toluene were
purchased from Kanto Chemical as dehydrated solvents and dried
over MS 4A. 4-(Dimethylamino)pyridine (DMAP) was purchased
from Tokyo Kasei Kogyo and used without further purification.
Iodine was purchased from Wako Pure Chemical Industries or
Aldrich Chemical and used without further purification. All re-
agents were purchased from Tokyo Kasei Kogyo, Kanto Chemi-
cal, Kokusan Chemical, Wako Pure Chemical Industries, or
Aldrich Chemical. Some carboxylic acids, alcohols, and !-hy-
droxycarboxylic acids were used after purification by distillation
or recrystallizaion. Other carboxylic acids,8 alcohols,8 and !-hy-
droxycarboxylic acids (n ¼ 11, 12)10 were prepared following
literature procedures.
O
O
O
OH
O
+
DMAP
CO
S
2b
R
O
O
S
O
3b
R
2
+
N
O
N
S
-O
S
(A)
N
-O
S
+
O
R
N
42
43
N
O
N
O
O
S
S
DMAP
4b
O
O
+
S
R
O
S
R'
R
O
1b
I
2
O
2b
I
I
-
(B)
O
S
O
R
R'
O
H
O
+
R
O
S
I
I
44
II
Di-2-thienyl Carbonate (2-DTC) (4b). Di-2-thienyl carbon-
ate was synthesized from 2(5H)-thiophenone. 2(5H)-Thiophenone
was purchased from Aldrich Chemical. After a mixture of 2(5H)-
thiophenone (100 mg, 1.0 mmol) and i-Pr2NEt (0.174 mL, 1.0
mmol) in CH3CN (3 mL) had been stirred for 10 minutes at room
temperature under an argon atmosphere, triphosgene (49.6 mg,
0.167 mmol) in CH3CN (1 mL) was added at ꢁ50 ꢂC, and the re-
action mixture was stirred for 2 h at ꢁ50 ꢂC. After evaporation of
the solvent, the residue was dissolved in ether and filtered. After
evaporation of the solvent, the residue was separated by short
silica-gel column chromatography (eluent: hexane/AcOEt =
12/1) and recrystallized from 2-propanol to afford 2-DTC (82.4
mg, 73%) as a colorless solid. The thus-prepared 2-DTC was sta-
ble crystalline and showed no sign of decomposition when kept
standing under argon at room temperature for over one month.
White powder. mp 53–54 ꢂC. IR (KBr, cmꢁ1) 1766. 1H NMR
(270 MHz, C6D6) ꢂ 6.47 (dd, J ¼ 3:2, 1.8 Hz, 2H), 6.35 (dd,
J ¼ 6:0, 3.2 Hz, 2H), 6.29 (dd, J ¼ 6:0, 1.8 Hz, 2H). 13C NMR
(68 MHz, C6D6) ꢂ 152.6, 150.2, 123.8, 118.5, 114.5. HRMS
(EIþ) calcd for C9H6O3S2 [M]þ 225.9758, found m=z 225.9784.
2-Thienyl 3-Phenylpropionate (7). Pale yellow oil. IR (neat,
cmꢁ1) 1758. 1H NMR (270 MHz, CDCl3) ꢂ 7.34–7.19 (m, 5H),
6.87 (dd, J ¼ 5:8, 1.9 Hz, 1H), 6.81 (dd, J ¼ 5:8, 3.9 Hz, 1H),
6.65 (dd, J ¼ 3:9, 1.9 Hz, 1H), 3.06 (t, J ¼ 7:4 Hz, 2H), 2.91–
2.83 (m, 2H). 13C NMR (68 MHz, CDCl3) ꢂ 169.3, 152.0,
140.0, 128.5, 128.2, 126.4, 123.2, 117.9, 113.2, 35.7, 30.7. HRMS
(EIþ) calcd for C13H12O2S [M]þ 232.0558, found m=z 232.0573.
Typical Experimental Procedure for the Synthesis of Car-
boxylic Esters by Using 2-DTC in the Presence of a Catalytic
Amount of DMAP (Method A). To a mixture of 3-phenylpro-
R'OH
Scheme 7. The reaction mechanism of esterification of car-
boxylic acid with alcohol using 2-DTC promoted by
DMAP and iodine.
Conclusion
It is noted that an effective method for the synthesis of var-
ious esters was developed by using nearly equimolar amounts
of free carboxylic acids including aromatic or hindered ones,
alcohols, and 2-DTC in the presence of a catalytic amount of
DMAP and an equimolar amount of iodine. Further, a simple
and effective method for the synthesis of various macrolac-
tones by using equimolar amounts of !-hydroxycarboxylic
acids and 2-DTC in the presence of a catalytic amount of
DMAP (5 mol %) and 1–4 equimolar amounts of iodine ac-
cording to an ordinary addition procedure was successfully es-
tablished under mild conditions. The utility of this 2-DTC
mediated lactonization method was demonstrated by the syn-
thesis of erythro-aleuritic acid lactone having an acid-sensitive
benzylidene protective group.
Experimental
General. All melting points were determined on a Yanagimoto
micro melting-point apparatus (Yanaco MP-S3) and were not
corrected. Infrared (IR) spectra were recorded on a JASCO
FT-IR 620 spectrometer, or a Horiba FT 710 FT-IR spectrometer.

Y. Oohashi et al.
Bull. Chem. Soc. Jpn., 78, No. 8 (2005) 1517
pionic acid (26.5 mg, 0.176 mmol) and 2-DTC (40.0 mg, 0.176
mmol) in CH2Cl2 (0.2 mL) was added DMAP (2.2 mg, 0.0176
mmol). After stirring for 10 minutes at room temperature, 3-phen-
yl-1-propanol (24.1 mg, 0.176 mmol) was added, and the mixture
was stirred for 6 h at room temperature. After evaporation of the
solvent, the crude product was purified by preparative thin-layer
chromatography to afford the corresponding ester (44.6 mg, 94%).
Typical Experimental Procedure for the Synthesis of Car-
boxylic Esters by Using 2-DTC Promoted by a Catalytic
Amount of DMAP and an Equimolar Amount of Iodine
174.4, 141.1, 140.6, 128.6, 128.3, 128.3, 127.5, 127.1, 125.9,
63.8, 45.5, 31.9, 30.1, 18.3. HRMS (EIþ) calcd for C18H20O2
[M]þ 268.1463, found m=z 268.1507.
Cyclohexyl 2-Phenylpropionate (15). Colorless oil. IR (neat,
cmꢁ1) 1730. 1H NMR (270 MHz, CDCl3) ꢂ 7.33–7.18 (m, 5H),
4.75 (m, 1H), 3.68 (q, J ¼ 7:0 Hz, 1H), 1.85–1.20 (m, 10H),
1.49 (d, J ¼ 7:0 Hz, 3H). 13C NMR (68 MHz, CDCl3) ꢂ 173.9,
140.8, 128.1, 127.2, 126.9, 72.6, 45.8, 31.4, 31.2, 28.6, 25.3,
23.5, 23.4, 18.4. HRMS (EIþ) calcd for C15H20O2 [M]þ
232.1463, found m=z 232.1502.
(Method B).
To a mixture of 3-phenylpropionic acid (26.5
3-Phenylpropyl Diphenylacetate (16).
Colorless oil. IR
1
mg, 0.176 mmol) and 2-DTC (40.0 mg, 0.176 mmol) in CH3CN
(0.2 mL) was added DMAP (1.08 mg, 0.0088 mmol). After stir-
ring for 10 minutes at room temperature, 3-phenyl-1-propanol
(28.8 mg, 0.211 mmol) and then iodine (47 mg, 0.185 mmol) were
added. The reaction mixture was stirred for 30 minutes at room
temperature, and then 10% aqueous sodium thiosulfate was added.
The mixture was extracted with ethyl acetate, and the organic lay-
er was washed with water and brine, and dried over anhydrous so-
dium sulfate. After filtration of the mixture and evaporation of the
solvent, the crude product was purified by preparative thin-layer
chromatography to afford the corresponding ester (44.3 mg, 94%).
3-Phenylpropyl 3-Phenylpropionate8 (8). Colorless oil. IR
(neat, cmꢁ1) 1735. H NMR (270 MHz, CDCl3) ꢂ 7.36–7.02 (m,
15H), 5.03 (s, 1H), 4.15 (t, J ¼ 6:5 Hz, 2H), 2.57 (t, J ¼ 7:7
Hz, 2H), 1.98–1.86 (m, 2H). 13C NMR (68 MHz, CDCl3) ꢂ
172.4, 141.0, 138.7, 128.6, 128.6, 128.6, 128.4, 127.2, 125.9,
64.3, 57.2, 31.9, 30.1. HRMS (EIþ) calcd for C23H22O2 [M]þ
330.1620, found m=z 330.1605.
1-Methyl-3-phenylpropyl Diphenylacetate (17). White crys-
tal. mp 59–60 ꢂC. IR (KBr, cmꢁ1) 1720. 1H NMR (270 MHz,
CDCl3) ꢂ 7.34–7.01 (m, 15H), 5.05–4.92 (m, 1H), 5.00 (s, 1H),
2.56–2.40 (m, 2H), 1.95–1.68 (m, 2H), 1.24 (d, J ¼ 6:2 Hz,
3H). 13C NMR (68 MHz, CDCl3) ꢂ 172.0, 141.5, 141.5, 138.8,
128.6, 128.6, 128.6, 128.5, 128.4, 128.3, 127.2, 127.2, 125.9,
71.3, 57.4, 37.6, 31.5, 19.9. HRMS (EIþ) calcd for C24H22O2
[M]þ 344.1776, found m=z 344.1816.
(neat, cmꢁ1) 1734. H NMR (270 MHz, CDCl3) ꢂ 7.32–7.11 (m,
1
10H), 4.08 (t, J ¼ 6:5 Hz, 2H), 2.95 (t, J ¼ 7:7 Hz, 2H), 2.68
(t, J ¼ 7:7 Hz, 4H), 1.94 (tt, J ¼ 7:7, 6.5 Hz, 2H). 13C NMR
(68 MHz, CDCl3) ꢂ 172.7, 141.0, 140.4, 128.4, 128.3, 128.3,
128.2, 126.1, 125.9, 63.8, 35.9, 32.2, 31.0, 30.2.
3-Phenylpropyl 3-(3-Pyridyl)propionate (18). Pale orange
oil. IR (neat, cmꢁ1) 1734. 1H NMR (270 MHz, CDCl3) ꢂ 8.49–
8.45 (m, 2H), 7.56–7.52 (m, 1H), 7.31–7.14 (m, 6H), 4.09 (t, J ¼
6:6 Hz, 2H), 2.95 (t, J ¼ 7:6 Hz, 2H), 2.64 (t, J ¼ 7:6 Hz, 4H),
1.94 (tt, J ¼ 7:6, 6.6 Hz, 2H). 13C NMR (68 MHz, CDCl3) ꢂ
172.1, 149.5, 147.5, 140.9, 135.9, 135.8, 128.3, 128.2, 125.9,
123.3, 64.0, 35.3, 32.2, 30.1, 28.1. HRMS (EIþ) calcd for
C17H19NO2 [M]þ 269.1416, found m=z 269.1395.
Benzyl 3-Phenylpropionate8 (9).
Colorless oil. IR (neat,
cmꢁ1) 1736. 1H NMR (270 MHz, CDCl3) ꢂ 7.39–7.17 (m,
10H), 5.11 (s, 2H), 2.97 (t, J ¼ 7:8 Hz, 2H), 2.68 (t, J ¼ 7:8
Hz, 2H). 13C NMR (68 MHz, CDCl3) ꢂ 172.5, 140.2, 135.7,
128.4, 128.4, 128.2, 128.2, 128.1, 126.1, 66.3, 36.0, 31.0.
1-Methyl-3-phenylpropyl 3-Phenylpropionate8 (10). Color-
less oil. IR (neat, cmꢁ1) 1731. 1H NMR (270 MHz, CDCl3) ꢂ
7.31–7.11 (m, 10H), 4.86 (tq, J ¼ 9:5, 6.3 Hz, 1H), 2.95 (t, J ¼
7:8 Hz, 2H), 2.66–2.48 (m, 2H), 2.60 (t, J ¼ 7:8 Hz, 2H), 1.96–
1.70 (m, 2H), 1.21 (d, J ¼ 6:2 Hz, 3H). 13C NMR (68 MHz,
CDCl3) ꢂ 172.3, 141.4, 140.4, 128.3, 128.3, 128.2, 128.2, 126.1,
125.8, 70.5, 37.6, 36.2, 31.8, 31.1, 20.1.
5-(Tetrahydropyranyloxy)pentyl 3-Phenylpropionate8 (19).
1
Colorless oil. IR (neat, cmꢁ1) 1735. H NMR (270 MHz, CDCl3)
ꢂ 7.32–7.16 (m, 5H), 4.58–4.56 (m, 1H), 4.07 (t, J ¼ 6:6 Hz, 2H),
3.91–3.85 (m, 1H), 3.78–3.68 (m, 1H), 3.54–3.46 (m, 1H), 3.42–
3.32 (m, 1H), 2.95 (t, J ¼ 7:8 Hz, 2H), 2.66–2.58 (m, 2H), 1.83–
1.32 (m, 12H). 13C NMR (68 MHz, CDCl3) ꢂ 172.8, 140.4, 128.3,
128.1, 126.1, 98.8, 67.3, 64.5, 62.3, 35.9, 31.0, 30.8, 29.4, 28.5,
25.5, 22.8, 19.7.
Cyclohexyl 3-Phenylpropionate8 (11).
Colorless oil. IR
(neat, cmꢁ1) 1731. H NMR (270 MHz, CDCl3) ꢂ 7.34–7.16 (m,
5H, Ph), 4.81–4.70 (m, 1H), 2.95 (t, J ¼ 7:8 Hz, 2H), 2.61 (t, J ¼
7:8 Hz, 4H), 1.84–1.21 (m, 10H). 13C NMR (68 MHz, CDCl3) ꢂ
172.2, 140.5, 128.3, 128.2, 126.1, 72.6, 36.3, 31.7, 31.1, 25.4,
23.8.
3-Phenylpropyl 3-(t-Butyldimethylsiloxy)-3-phenylpropio-
1
1
nate8 (20). Colorless oil. IR (neat, cmꢁ1) 1737. H NMR (270
MHz, CDCl3) ꢂ 7.32–7.12 (m, 10H), 5.13 (dd, J ¼ 9:2, 4.3 Hz,
1H), 4.12–4.02 (m, 2H), 2.78–2.61 (m, 2H), 2.54 (dd, J ¼ 14:9,
4.3 Hz, 2H), 1.98–1.87 (m, 2H), 0.82 (s, 9H), 0.00 (s, 3H),
ꢁ0:19 (s, 3H). 13C NMR (68 MHz, CDCl3) ꢂ 171.0, 143.9,
141.1, 128.3, 128.3, 128.2, 127.4, 125.9, 125.7, 72.2, 63.9, 46.4,
32.2, 30.2, 25.7, 18.1, ꢁ4:6, ꢁ5:1.
Phenyl 3-Phenylpropionate15 (12). Colorless oil. IR (neat,
cmꢁ1) 1759. 1H NMR (270 MHz, CDCl3) ꢂ 7.39–6.97 (m,
10H), 3.08 (t, J ¼ 7:4 Hz, 2H), 2.88 (t, J ¼ 7:4 Hz, 2H). 13C NMR
(68 MHz, CDCl3) ꢂ 171.2, 150.4, 140.0, 129.3, 128.5, 128.3,
126.3, 125.7, 121.4, 36.0, 31.0.
3-Phenylpropyl (E)-3-Phenyl-2-propenoate8 (21). Colorless
oil. IR (neat, cmꢁ1) 1712. 1H NMR (270 MHz, CDCl3) ꢂ 7.68 (d,
J ¼ 16:1 Hz, 1H), 7.59–7.51 (m, 2H), 7.41–7.15 (m, 8H), 6.45 (d,
J ¼ 16:1 Hz, 1H), 4.23 (t, J ¼ 6:5 Hz, 2H), 2.75 (t, J ¼ 7:7 Hz,
2H), 2.04 (tt, J ¼ 7:7, 6.5 Hz, 2H). 13C NMR (68 MHz, CDCl3)
ꢂ 166.9, 144.6, 141.1, 134.3, 130.2, 128.8, 128.3, 128.3, 128,
125.9, 118, 63.9, 32.3, 30.4.
3-Phenylpropyl Cyclohexanecarboxylate8 (13). Colorless
oil. IR (neat, cmꢁ1) 1732. 1H NMR (270 MHz, CDCl3) ꢂ 7.32–
7.16 (m, 5H), 4.08 (t, J ¼ 6:6 Hz, 2H), 2.69 (t, J ¼ 7:7 Hz,
2H), 2.35–2.24 (m, 1H), 2.00–1.88 (m, 4H), 1.78–1.63 (m, 2H),
1.52–1.12 (m, 6H). 13C NMR (68 MHz, CDCl3) ꢂ 176.0, 141.1,
128.3, 128.3, 125.8, 63.4, 43.3, 32.2, 30.3, 29.1, 25.8, 25.5.
3-Phenylpropyl 2-Phenylpropionate (14). Colorless oil. IR
3-Phenylpropyl Benzoate8 (22).
Colorless oil. IR (neat,
cmꢁ1) 1718. 1H NMR (270 MHz, CDCl3) ꢂ 7.85–7.81 (m, 2H),
7.54–7.05 (m, 8H), 4.34 (t, J ¼ 6:5 Hz, 2H), 2.77 (t, J ¼ 7:7
Hz, 2H), 2.16–2.06 (m, 2H). 13C NMR (68 MHz, CDCl3) ꢂ
166.4, 141.0, 132.8, 130.2, 129.4, 128.3, 128.3, 128.2, 125.9,
64.2, 32.3, 30.3.
(neat, cmꢁ1) 1733. H NMR (270 MHz, CDCl3) ꢂ 7.36–7.13 (m,
1
8H), 7.06–7.03 (m, 2H), 4.06 (t, J ¼ 6:3 Hz, 2H), 3.72 (q, J ¼
7:2 Hz, 1H), 2.54 (t, J ¼ 7:7 Hz, 2H), 1.88 (tt, J ¼ 7:7, 6.3 Hz,
2H), 1.51 (d, J ¼ 7:2 Hz, 3H). 13C NMR (68 MHz, CDCl3) ꢂ

1518 Bull. Chem. Soc. Jpn., 78, No. 8 (2005)
2-DTC Mediated Esterification Reactions
3-Phenylpropyl 2,2-Dimethylpropionate8 (23).
Colorless
(neat, cmꢁ1) 1712. 1H NMR (270 MHz, CDCl3) ꢂ 7.98 (d, J ¼ 8:9
Hz, 2H), 7.32–7.15 (m, 5H), 6.92 (d, J ¼ 8:9 Hz, 2H), 4.31 (t, J ¼
6:2 Hz, 2H), 3.85 (s, 3H), 2.78 (t, J ¼ 7:3 Hz, 2H), 2.15–2.05 (m,
2H). 13C NMR (68 MHz, CDCl3) ꢂ 166.2, 163.1, 141.1, 131.4,
128.3, 128.3, 125.9, 122.7, 113.5, 64.0, 55.4, 32.4, 30.4.
Phenyl 4-Chlorobenzoate16 (34). White crystal. mp 102–103
ꢂC. IR (KBr, cmꢁ1) 1733. 1H NMR (270 MHz, CDCl3) ꢂ 8.16–
8.12 (m, 2H), 7.50–7.40 (m, 4H), 7.35–7.20 (m, 3H). 13C NMR
(68 MHz, CDCl3) ꢂ 164.2, 150.6, 140.0, 131.4, 129.4, 128.8,
127.9, 125.9, 121.5.
oil. IR (neat, cmꢁ1) 1729. 1H NMR (270 MHz, CDCl3) ꢂ 7.32–
7.14 (m, 5H), 4.07 (t, J ¼ 6:3 Hz, 2H), 2.69 (t, J ¼ 7:7 Hz,
2H), 1.96 (tt, J ¼ 7:7, 6.3 Hz, 2H), 1.21 (s, 9H). 13C NMR (68
MHz, CDCl3) ꢂ 178.4, 141.1, 128.3, 128.3, 125.9, 63.5, 38.8,
32.2, 30.3, 27.3.
1-Methyl-3-phenylpropyl Cyclohexanecarboxylate8 (25).
1
Colorless oil. IR (neat, cmꢁ1) 1729. H NMR (270 MHz, CDCl3)
ꢂ 7.31–7.13 (m, 5H), 4.99–4.87 (m, 1H), 2.73–2.53 (m, 2H), 2.32–
2.21 (m, 1H), 1.97–1.18 (m, 12H), 1.23 (d, J ¼ 6:2 Hz, 3H).
13C NMR (68 MHz, CDCl3) ꢂ 175.5, 141.5, 128.3, 128.2, 125.8,
69.8, 43.5, 37.8, 31.9, 29.2, 29.0, 25.8, 25.6, 25.5, 20.1.
Phenyl 4-(Trifluoromethyl)benzoate16 (35). White crystal.
mp 89–90 ꢂC. IR (KBr, cmꢁ1) 1735. 1H NMR (270 MHz, CDCl3)
ꢂ 8.32 (d, J ¼ 8:1 Hz, 2H), 7.77 (d, J ¼ 8:1 Hz, 2H), 7.47–7.41
(m, 2H), 7.32–7.18 (m, 3H). 13C NMR (68 MHz, CDCl3) ꢂ
163.8, 150.5, 134.9 (q, 2J (13C,19F) = 32.95 Hz), 132.7 (d, 4J
(13C,19F) = 1.15 Hz), 130.4, 129.5, 126.1, 125.5 (q, 3J
Cyclohexyl Cyclohexanecarboxylate8 (26). Colorless oil. IR
1
(neat, cmꢁ1) 1729. H NMR (270 MHz, CDCl3) ꢂ 4.81–4.68 (m,
1H), 2.31–2.20 (m, 1H), 1.91–1.19 (m, 20H). 13C NMR (68
MHz, CDCl3) ꢂ 175.3, 71.8, 43.4, 31.6, 29.1, 25.8, 25.5, 25.5,
23.7.
1
(13C,19F) = 3.86 Hz), 123.7 (q, J (13C,19F) = 273.5 Hz), 121.4.
1-Methyl-3-phenylpropyl 2,2-Dimethylpropionate8 (27).
Phenyl 4-Nitrobenzoate16 (36). White crystal. mp 127–128
ꢂC. IR (KBr, cmꢁ1) 1742. 1H NMR (270 MHz, CDCl3) ꢂ 8.41–
8.33 (m, 4H), 7.50–7.40 (m, 2H), 7.35–7.20 (m, 3H). 13C NMR
(68 MHz, CDCl3) ꢂ 163.2, 150.7, 150.3, 134.8, 131.2, 130.0,
126.3, 123.6, 121.3.
1
Colorless oil. IR (neat, cmꢁ1) 1725. H NMR (270 MHz, CDCl3)
ꢂ 7.35–7.15 (m, 5H), 4.97–4.85 (m, 1H), 2.75–2.52 (m, 2H), 2.00–
1.71 (m, 2H), 1.24 (d, J ¼ 7:3 Hz, 3H), 1.21 (s, 9H). 13C NMR (68
MHz, CDCl3) ꢂ 177.9, 141.5, 128.3, 128.2, 125.8, 70.0, 38.8,
37.8, 31.9, 27.3, 20.0.
Typical Experimental Procedure for the Synthesis of Lac-
tones by Using 2-DTC. To a mixture of 12-hydroxydodecanoic
acid (38.1 mg, 0.176 mmol) and 2-DTC (40.0 mg, 0.176 mmol) in
CH3CN (10 mL) was added DMAP (1.08 mg, 0.0088 mmol). Af-
ter stirring for 15 minutes at room temperature, the resultant solu-
tion was diluted by the addition of 166 mL of toluene and treated
with iodine (179 mg, 0.707 mmol). The reaction mixture was stir-
red for 10 h at the reflux temperature of toluene and then cooled to
room temperature. Then, 10% aqueous sodium thiosulfate was
added and CH3CN and toluene were evaporated. The mixture
was extracted with ethyl acetate, and the organic layer was washed
with water and brine, and dried over anhydrous sodium sulfate.
After filtration of the mixture and evaporation of the solvent,
the crude product was purified by preparative thin-layer chroma-
tography to afford the corresponding lactone (26.8 mg, 77%).
2-Thienyl 12-Hydroxydodecanoate (38). White crystal. mp
69–70 ꢂC. IR (KBr, cmꢁ1) 3367, 1749. 1H NMR (270 MHz,
CDCl3) ꢂ 6.88 (dd, J ¼ 5:8, 1.6 Hz, 1H), 6.82 (dd, J ¼ 5:8, 3.8
Hz, 1H), 6.68 (dd, J ¼ 3:8, 1.6 Hz, 1H), 3.63 (t, J ¼ 6:6 Hz,
2H), 2.55 (t, J ¼ 7:5 Hz, 2H), 1.79–1.67 (m, 2H), 1.67–1.51 (m,
2H), 1.45–1.20 (m, 14H). 13C NMR (68 MHz, CDCl3) ꢂ 170.4,
152.0, 123.2, 117.9, 113.1, 63.1, 34.0, 32.8, 29.5, 29.5, 29.4,
29.4, 29.2, 29.0, 25.7, 24.7. HRMS (FABþ) calcd for C16H27O3S
½M þ Hꢃþ 299.1681, found m=z 299.1685.
1-Methyl-3-phenylpropyl (E)-3-Phenyl-2-propenoate8 (28).
1
Colorless oil. IR (neat, cmꢁ1) 1710. H NMR (270 MHz, CDCl3)
ꢂ 7.67 (d, J ¼ 16:1 Hz, 1H), 7.53–7.51 (m, 2H), 7.39–7.15 (m,
8H), 6.43 (d, J ¼ 16:1 Hz, 1H), 5.14–5.02 (m, 1H), 2.80–2.63
(m, 2H), 2.04–1.80 (m, 1H), 1.96–1.81 (m, 1H), 1.33 (d, J ¼
6:2 Hz, 3H). 13C NMR (68 MHz, CDCl3) ꢂ 166.5, 144.3, 141.4,
134.3, 130.1, 128.8, 128.3, 128.2, 128.0, 125.8, 118.5, 70.6,
37.8, 31.9, 20.2.
3-Phenylpropyl (E)-Crotonate8 (29). Colorless oil. IR (neat,
cmꢁ1) 1719. 1H NMR (270 MHz, CDCl3) ꢂ 7.31–7.16 (m, 5H),
6.97 (dq, J ¼ 15:4, 7.0 Hz, 1H), 5.84 (dq, J ¼ 15:4, 1.8 Hz,
1H), 4.14 (t, J ¼ 6:5 Hz, 2H), 2.70 (t, J ¼ 7:7 Hz, 2H), 2.03–
1.90 (m, 2H), 1.88 (dd, J ¼ 7:0, 1.8 Hz, 3H). 13C NMR (68
MHz, CDCl3) ꢂ 166.4, 144.5, 141.1, 128.3, 128.3, 125.8, 122.5,
63.5, 32.2, 30.3, 18.1.
1-Methyl-3-phenylpropyl (E)-Crotonate8 (30). Colorless oil.
1
IR (neat, cmꢁ1) 1717. H NMR (270 MHz, CDCl3) ꢂ 7.30–7.15
(m, 5H), 6.96 (dq, J ¼ 15:4, 7.0 Hz, 1H), 5.84 (dq, J ¼ 15:4,
1.8 Hz, 1H), 5.05–4.93 (m, 1H), 2.75–2.55 (m, 2H), 2.06–1.75
(m, 2H), 1.88 (dd, J ¼ 7:0, 1.8 Hz, 3H), 1.27 (d, J ¼ 6:5 Hz,
3H). 13C NMR (68 MHz, CDCl3) ꢂ 166.0, 144.1, 141.5, 128.3,
128.2, 125.7, 123.0, 70.1, 37.8, 31.8, 20.2, 18.0.
3-Phenylpropyl 4-Phenyl-3-butenoate (31). Colorless oil. IR
(neat, cmꢁ1) 1735. H NMR (270 MHz, CDCl3) ꢂ 7.42–7.10 (m,
1
Undecan-11-olide10 (12-Membered Ring Lactone). Color-
less oil. IR (neat, cmꢁ1) 1735. 1H NMR (270 MHz, CDCl3) ꢂ
4.20 (t, J ¼ 5:2 Hz, 2H), 2.40–2.33 (m, 2H), 1.80–1.60 (m, 4H),
1.60–1.47 (m, 2H), 1.47–1.23 (m, 10H). MS (EIþ) m=z 184 [M]þ.
Dodecan-12-olide8 (13-Membered Ring Lactone). Colorless
10H), 6.50 (d, J ¼ 16:2 Hz, 1H), 6.30 (dt, J ¼ 16:2, 6.8 Hz,
1H), 4.16 (t, J ¼ 6:2 Hz, 2H), 3.24 (d, J ¼ 6:8 Hz, 2H), 2.70 (t,
J ¼ 7:7 Hz, 2H), 2.05–1.91 (m, 2H). 13C NMR (68 MHz, CDCl3)
ꢂ 171.6, 141.1, 136.8, 133.4, 128.5, 128.4, 128.4, 127.5, 126.3,
126.0, 121.7, 64.1, 38.4, 32.1, 30.1. HRMS (FABþ) calcd for
C19H21O2 ½M þ Hꢃþ 281.1542, found m=z 281.1519.
1
oil. IR (neat, cmꢁ1) 1734. H NMR (270 MHz, CDCl3) ꢂ 4.15 (t,
J ¼ 5:3 Hz, 2H), 2.38–2.33 (m, 2H), 1.73–1.60 (m, 4H), 1.48–
3-Phenylpropyl 3-Hexenoate (32). Colorless oil. IR (neat,
cmꢁ1) 1737. 1H NMR (270 MHz, CDCl3) ꢂ 7.32–7.15 (m, 5H),
5.63 (dt, J ¼ 16:1, 6.3 Hz, 1H), 5.53 (dt, J ¼ 16:1, 6.1 Hz, 1H),
4.10 (t, J ¼ 6:6 Hz, 2H), 3.03 (d, J ¼ 6:3 Hz, 2H), 2.69 (t, J ¼
7:3 Hz, 2H), 2.11–1.91 (m, 4H), 1.00 (t, J ¼ 7:4 Hz, 3H).
13C NMR (68 MHz, CDCl3) ꢂ 172.3, 141.2, 136.3, 128.4, 128.4,
126.0, 120.6, 63.8, 38.1, 32.1, 30.2, 25.5, 13.4. HRMS (FABþ)
calcd for C15H20AgO2 ½M þ Agꢃþ 339.0514, found m=z 339.0524.
3-Phenylpropyl 4-Methoxybenzoate15 (33). Colorless oil. IR
1.25 (m, 14H). MS (EIþ) m=z 198 [M]þ.
Tridecan-13-olide8 (14-Membered Ring Lactone). Color-
less oil. IR (neat, cmꢁ1) 1735. 1H NMR (270 MHz, CDCl3) ꢂ
4.15 (t, J ¼ 5:4 Hz, 2H), 2.40–2.35 (m, 2H), 1.72–1.59 (m, 4H),
1.50–1.21 (m, 16H). MS (EIþ) m=z 212 [M]þ.
Tetradecan-14-olide8 (15-Membered Ring Lactone). Color-
less oil. IR (neat, cmꢁ1) 1736. 1H NMR (270 MHz, CDCl3) ꢂ 4.14
(t, J ¼ 5:3 Hz, 2H), 2.37–2.32 (m, 2H), 1.74–1.58 (m, 4H), 1.45–
1.20 (m, 18H). MS (EIþ) m=z 226 [M]þ.

Y. Oohashi et al.
Bull. Chem. Soc. Jpn., 78, No. 8 (2005) 1519
Pentadecan-15-olide8 (16-Membered Ring Lactone). Color-
less oil. IR (neat, cmꢁ1) 1737. 1H NMR (270 MHz, CDCl3) ꢂ 4.13
(t, J ¼ 5:5 Hz, 2H), 2.33 (t, J ¼ 6:8 Hz, 2H), 1.72–1.58 (m, 4H),
1.44–1.24 (m, 20H). MS (FABþ) m=z 241 ½M þ Hꢃþ.
Ko, Tetrahedron Lett., 25, 4943 (1984).
O,O0-Di(2-pyridyl) thiocarbonate (DPTC): K. Saitoh, I.
Shiina, and T. Mukaiyama, Chem. Lett., 1998, 679.
2-Methyl-6-nitrobenzoic anhydride (MNBA): I. Shiina,
R. Ibuka, and M. Kubota, Chem. Lett., 2002, 286; I. Shiina, M.
Kubota, and R. Ibuka, Tetrahedron Lett., 43, 7535 (2002); I.
Shiina, M. Kubota, H. Oshiumi, and M. Hashizume, J. Org.
Chem., 69, 1822 (2004).
7
8
Hexadecan-16-olide8 (17-Membered Ring Lactone). Color-
less oil. IR (neat, cmꢁ1) 1737. 1H NMR (270 MHz, CDCl3) ꢂ 4.12
(t, J ¼ 5:6 Hz, 2H), 2.32 (t, J ¼ 6:6 Hz, 2H), 1.72–1.58 (m, 4H),
1.43–1.20 (m, 22H). MS (FABþ) m=z 255 ½M þ Hꢃþ.
erythro-9,10-Benzylidenedioxyhexadecan-16-olide8
(40).
9
4-(Trifluoromethyl)benzoic anhydride: I. Shiina, S.
White crystal. mp 56–57 ꢂC. IR (KBr, cmꢁ1) 1732. 1H NMR
(270 MHz, CDCl3) ꢂ 7.75–7.66 (m, 2H), 7.28–7.10 (m, 3H),
6.03 (1H, s), 4.08–4.02 (m, 2H), 3.88–3.71 (m, 2H), 2.19 (t, J ¼
7:0 Hz, 2H), 1.94–1.01 (m, 22H). MS (ESIþ) m=z 397 ½M þ Naꢃþ.
Miyoshi, M. Miyashita, and T. Mukaiyama, Chem. Lett., 1994,
515; I. Shiina and T. Mukaiyama, Chem. Lett., 1994, 677; I.
Shiina, Tetrahedron, 60, 1587 (2004).
10 4-Nitrobenzoic anhydride/Sc(OTf)3: K. Ishihara, M.
Kubota, H. Kurihara, and H. Yamamoto, J. Org. Chem., 61,
4560 (1996).
This study was supported in part by the Grant of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT).
The authors wish to thank Mr. Hiroshi Oe, Mr. Masaharu
Gotoda, and Mrs Mami Gomibuchi, and Eisai Pharmaceutical
Company for their kind help with IR, MS, and high-resolution
mass spectrometry.
11 H. A. Staab and A. Mannschreck, Chem. Ber., 95, 1284
(1962); J. D. Meseguer, A. L. P. Coll, J. R. F. Lizarbe, and
A. Z. Bilbao, Synthesis, 1980, 547; K. Takeda, A. Akiyama, H.
Nakamura, S. Takizawa, Y. Mizuno, H. Takayanagi, and Y.
Harigaya, Synthesis, 1994, 1063; K. Wakasugi, A. Nakamura,
and Y. Tanabe, Tetrahedron Lett., 42, 7427 (2001); K. Wakasugi,
A. Nakamura, A. Iida, Y. Nishii, N. Nakatani, S. Fukushima, and
Y. Tanabe, Tetrahedron, 59, 5337 (2003); K. Wakasugi, A. Iida,
T. Misaki, Y. Nishii, and Y. Tanabe, Adv. Synth. Catal., 345,
1209 (2003); I. Shiina and Y. Kawakita, Tetrahedron Lett., 44,
1951 (2003); I. Shiina, Y. Fukuda, T. Ishii, H. Fujisawa, and T.
Mukaiyama, Chem. Lett., 1998, 831; I. Shiina, H. Fujisawa, T.
Ishii, and Y. Fukuda, Heterocycles, 52, 1105 (2000); L. Gooßen
and A. Dohring, Adv. Synth. Catal., 345, 943 (2003).
12 T. Mukaiyama, Y. Oohashi, and K. Fukumoto, Chem. Lett.,
33, 552 (2004).
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6