Chemistry Letters Vol.33, No.8 (2004)
969
molar amount of DMAP (0.1 equiv.)9 But, no product was
formed when an equimolar amount of iodine was used instead
of DMAP under the above conditions (Step 1). The correspond-
Table 2. Esterification using various alcohols
O
O
2-DTC (1.0 equiv.) R'OH (1.2 equiv.)
Ph
OH
1.0 equiv.)
9
DMAP (0.05 equiv.) I2 (1.05 equiv.) Ph
OR'
ing ester 2 in the previous report was obtained in 4 h by the acy-
(
CH CN, rt
lation of 3-phenyl-1-propanol with isolated thienyl ester 1 in the
presence of DMAP. On the other hand, it is noted that the above
reaction proceeded within 30 min in the presence of iodine to af-
ford the ester 2 in high yield (Step 2). These results indicate that
a catalytic amount of DMAP behaved effectively in the first step
and iodine worked efficiently in the second step. The detailed
mechanism of the activation of thienyl esters with iodine is
now under investigation.
It is noted that a simple and effective method for the synthe-
sis of various esters was established by using nearly equimolar
amounts of free carboxylic acids including aromatic and hin-
dered ones, alcohols and 2-DTC in the presence of a catalytic
amount of DMAP and an equimolar amount of iodine.
3
Time ( )a
Yield ( )a
/%
Entry
R’OH
/h
1
2
Rh(CH2)3OH
CH3(CH2)3OH
BnOH
0.5 (6)
0.5 (8)
0.5 (4)
0.5 (8)
94 (94)
86 (91)
89 (96)
90 (82)
88 (81)
3
4
Ph(CH2)2CH(OH)CH3
c-C6H11OH
5
1
(11)
a
Values in parentheses are those obtained previously in CH2Cl2 in the pres-
ence of 0.1 equiv. of DMAP.9
Table 3. Esterification using various carboxylic acids and
alcohols
O
O
2
-DTC (1.0 equiv.)
R'OH (1.2 equiv.)
I2 (1.05 equiv.)
R
OH
R
OR'
References and Notes
DMAP (0.05 equiv.)
(
1.0 equiv.)
1
2
B. Neises and W. Steglich, Angew. Chem., Int. Ed. Engl., 17, 522
1978); A. Hssner and V. Alexanian, Tetrahedron Lett., 1978,
4475.
J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, and M. Yamaguchi,
Bull. Chem. Soc. Jpn., 52, 1989 (1979).
CH CN, rt
3
(
Time ( )a Yield( )a
Entry
RCO2H
R’OH
/h
/%
86
1
2
3
4
5
6
7
8
9
CH3(CH2)3COOH
PhMeCHCOOH
PhMeCHCOOH
c-C6H11COOH
c-C6H11COOH
Me3CCOOH
Ph(CH2)3OH
Ph(CH2)3OH
c-C6H11OH
Ph(CH2)3OH
0.5
2
b
(6)
(11) 81 (83)
93 (79)
c
3
4
5
S. Kim, J. I. Lee, and Y. K. Ko, Tetrahedron Lett., 25, 4943 (1984).
K. Saitoh, I. Shiina, and T. Mukaiyama, Chem. Lett., 1998, 679.
I. Shiina, R. Ibuka, and M. Kubota, Chem. Lett., 2002, 286; I.
Shiina, M. Kubota, and R. Ibuka, Tetrahedron Lett., 43, 7535
2
0.5 (11) 91 (87)
Ph(CH2)2CH(OH)CH3 0.5 (48) 93b (69)
Ph(CH2)3OH 0.5 (22) 91 (N.D.)
Ph(CH2)2CH(OH)CH3 0.5 81
Ph(CH2)3OH 0.5 (22) 88 (37)
(
2002).
Me3CCOOH
(E)-PhCH=CHCOOH
6
I. Shiina, S. Miyoshi, M. Miyashita, and T. Mukaiyama, Chem.
Lett., 1994, 515; I. Shiina and T. Mukaiyama, Chem. Lett., 1994,
(E)-PhCH=CHCOOH Ph(CH2)2CH(OH)CH3 0.5
83
(22) 89 (33)
6
77; I. Shiina, Tetrahedron, 60, 1587 (2004).
1
0
1
PhCOOH
p-MeOPhCOOH
Ph(CH2)3OH
Ph(CH2)3OH
6
0.5 (22) 87 (3)
7
8
K. Ishihara, M. Kubota, H. Kurihara, and H. Yamamoto, J. Org.
Chem., 61, 4560 (1996).
1
a
Values in parentheses are those obtained previously in CH2Cl2 in the presence
of 0.1 equiv. of DMAP.9
K. Saigo, M. Usui, K. Kikuchi, E. Shimada, and T. Mukaiyama,
Bull. Chem. Soc. Jpn., 50, 1863 (1977); 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,
b
Reactions were performed by using 0.1 equiv. of DMAP and 1.1 equiv. of
iodine and CH2Cl2 as a solvent.
c
Reactions were performed by using 0.1 equiv. of DMAP and 1.5 equiv. of
iodine and CH2Cl2 as a solvent.
hols proceeded smoothly to afford the corresponding esters in
good to high yields by using nearly equimolar amounts of pri-
mary alcohols (Table 2, Entries 1–3). Also, the esters were ob-
tained in good to high yields when secondary alcohols were used
(Entries 4, 5). It is interesting to note that these reactions com-
pleted quickly in the presence of iodine i.e. 30 min–1 h whereas
7
427 (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
9
it took much longer i.e. 4–11 h in the absence of iodine.
(2000); L. Gooßen and A. Dohring, Adv. Synth. Catal., 345, 943
(2003).
The results of the esterification using various carboxylic
acids are listed in Table 3. The corresponding ester was obtained
in good yield by using n-valeric acid (Entry 1). Also, the desired
products were obtained rapidly in good to high yields even when
9
1
T. Mukaiyama, Y. Oohashi, and K. Fukumoto, Chem. Lett., 33,
52 (2004).
0 A typical experimental procedure was as follows: to a mixture of
-phenylpropionic acid (26.5 mg, 0.176 mmol) and 2-DTC (40.0
5
ꢀ
,ꢀ-disubstituted carboxylic acids and secondary alcohols were
3
used (Entries 3, 5). In the cases of trans-cinnamic acid and aro-
matic acids or a hindered carboxylic acid such as pivalic acid,
the esters were likewise obtained rapidly in good to high yields
whereas the former two acids gave the corresponding esters in
low yields and the latter one did not form the ester at all under
mg, 0.176 mmol) in CH CN (0.2 mL) was added DMAP (1.08
3
mg, 0.0088 mmol). After stirring for 10 min at room temperature,
3
-phenyl-1-propanol (28.8 mg, 0.211 mmol) and then iodine (47
mg, 0.185 mmol) was added. The reaction mixture was stirred
for 30 min at room temperature and then 10% aqueous sodium thi-
osulfate was added. The mixture was extracted with ethyl acetate,
and the organic layer was washed with water and brine, dried over
sodium sulfate. After filtration of the mixture and evaporation of
the solvent, the crude product was purified by preparative thin lay-
er chromatography to afford the corresponding ester (44.3 mg,
94%).
9
previously reported conditions (Entries 6–11).
The above procedure consists of two reactions. As describ-
ed, thienyl ester 1 was formed immediately by treating carbox-
ylic acid with 2-DTC in the presence of DMAP (0.05 equiv.)
in CH3CN whereas the reaction in CH2Cl2 needed to use more
Published on the web (Advance View) July 5, 2004; DOI 10.1246/cl.2004.968