Efficient method for the esterification of carboxylic acids with alcohols using di-2-thienyl carbonate promoted by catalytic amounts of DMAP and Hf(OTf)4

Article abstract of DOI:10.1246/cl.2005.190

Esterification of carboxylic acids with alcohols including bulky secondary ones by using an equimolar amount of di-2-thienyl carbonate (2-DTC) in the presence of a catalytic amount of 4-(dimethylamino)pyridine (DMAP) followed by addition of a catalytic amount of hafnium(IV) trifluoromethanesulfonate (Hf(OTf)₄) afforded the corresponding esters in good to high yields. Copyright

Full text of DOI:10.1246/cl.2005.190

190
Chemistry Letters Vol.34, No.2 (2005)
Efficient Method for the Esterification of Carboxylic Acids with Alcohols
Using Di-2-thienyl Carbonate Promoted by Catalytic Amounts of DMAP and Hf(OTf)4
Yoshiaki Oohashi,y Kentarou Fukumoto,y and Teruaki Mukaiyamaꢀy;yy
yCenter for Basic Research, The Kitasato Institute, 6-15-5 (TCI) Toshima, Kita-ku, Tokyo 114-0003
yyKitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received November 8, 2004; CL-041336)
Esterification of carboxylic acids with alcohols including
Table 1. Esterification of 2-thienyl 3-phenylpropionate by
using silyl ether or alcohol using various Lewis acids
bulky secondary ones by using an equimolar amount of di-2-
thienyl carbonate (2-DTC) in the presence of a catalytic amount
of 4-(dimethylamino)pyridine (DMAP) followed by addition of
a catalytic amount of hafnium(IV) trifluoromethanesulfonate
(Hf(OTf)4) afforded the corresponding esters in good to high
yields.
Ph(CH2)3OR
(1.2 equiv.)
O
O
Lewis acid
(0.1 equiv.)
CH3CN, rt
Ph
O
S
Ph
O
Ph
1
(1.0 equiv.)
2
R=TMS
R=H
Entry
Lewis acid
Time/h
Yield/%
Time/h
Yield/%
Preparation of carboxylic esters from nearly equimolar
amounts of carboxylic acids and alcohols is one of the most im-
portant and fundamental methods in synthetic organic chemistry.
Therefore, several useful methods for those esterifications have
been developed1–8 and are widely employed in the synthesis of
natural or unnatural molecules that have carboxylic ester moie-
ties.
1
2
BF3-OEt2
TiCl4
4
N.R.
9
4
7
17
16
66
2
4
4
3
SnCl4
4
82
4
4
HfCl4
4
65
4
5
Mg(OTf)2
Cu(OTf)2
Sc(OTf)3
Hf(OTf)4
La(OTf)3
Gd(OTf)3
Yb(OTf)3
4
24
4
6
0.5
4
quant.
86
4
6
7
4
29
92
N.R.
4
8
0.5
4
quant.
trace
5
0.5
4
In our previous communication, a new method for the above
esterification was reported by using di-2-thienyl carbonate
(2-DTC) in the presence of a catalytic amount of 4-(dimethyl-
amino)pyridine (DMAP).9 Recently, it was reported from our
laboratory that the further addition of an equimolar amount of
iodine accelerated this esterification and the yield was
improved.10 But, this reaction did not proceed satisfactorily
when a catalytic amount of iodine was used. Also, this method
did not afford the corresponding esters in satisfactory yields
when the substrates containing an olefinic moiety such as allyl
alcohol or hexenoic acid were used. Now, in order to improve
the utility of 2-DTC mediated esterification, the above reaction
was tried by using several Lewis acids. In this communication,
a newly developed 2-DTC-mediated highly efficient ester-
9
10
11
4
4
4
7
4
7
(OTf)4
Hf
O
O
O
S
Hf (OTf)4
R'OH
+
R'
R
O
S
O
S
R
O
R
O
I
Scheme 1. The active chelate complex I derived from 2-thienyl
ester and Hf(OTf)4.
Hf(OTf)4 at carbonyl oxygen and sulfur atoms of thienyl ester.
The complex I subsequently reacted with alcohol to afford the
corresponding ester because an alcohol hardly coordinate further
to complex I that is fully saturated by ligands (Scheme 1). On the
other hand, group 3 metal triflates such as Sc(OTf)3 and
Ln(OTf)3 are assumed to form chelate complexes II which are
still not fully occupied by ligands. Then further coordination
of alcohol results in the formation of the chelate complexes
III. They are considered to be deactivated because of decrease
in Lewis acidity of metal triflates (Scheme 2). Thus, the reaction
of 1 with 3-phenyl-1-propanol using group 3 metal triflates did
not proceed effectively (Table 1, Entries 7, 9–11).
11
forming reaction by using DMAP and Hf(OTf)4 is described.
In the first place, effect of various Lewis acid catalysts was
screened by taking the reaction of 2-thienyl 3-phenylpropionate
1 with 3-phenyl-1-propyl trimethylsilyl ether as a model
(Table 1). In the cases when typical Lewis acids were used
(Entries 1–3), none or only a small amount of desired ester 2
was obtained except when SnCl4 was used. Then, reactions in
the presence of various Lewis acid catalysts, as metal triflates,
were screened. As a consequence, the corresponding ester 2
was obtained in high yields when catalysts such as Cu(OTf)2,
Sc(OTf)3, or Hf(OTf)4 were used (Entries 6–8). Next, the reac-
tion of 2-thienyl 3-phenylpropionate 1 with 3-phenyl-1-propanol
was examined in the presence of catalytic amounts of various
Lewis acids. The desired ester 2 was obtained in high yield only
when Hf(OTf)4 was used (Entry 8). It was interesting to note that
Hf(OTf)4 worked more effectively than Sc(OTf)3 which was
known as a remarkably active Lewis acid catalyst for the acyla-
tion of alcohols with acid anhydrides7 (Entries 7, 8).
H
(OTf)3
(OTf)3
O
R'
M
S
M
O
S
O
O
M (OTf)3
R'OH
R
O
S
R
O
R
O
III
II
These results are explained by considering an initial forma-
tion of the active chelate complex I by the interaction of
Scheme 2. The deactivation of chelate complex II by further
coordination of alcohol.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.2 (2005)
191
Table 2. Esterification of various alcohols in the presence of
DMAP and Hf(OTf)4
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan.
O
O
2-DTC (1.0 equiv.)
R'OH (1.2 equiv.)
References and Notes
R
OR'
R
OH
1
2
DCC: B. Neises and W. Steglich, Angew. Chem., Int. Ed. Engl.,
17, 522 (1978); A. Hassner and V. Alexanian, Tetrahedron
Lett., 19, 4475 (1978).
2,4,6-Trichlorobenzoyl chloride: J. Inanaga, K. Hirata, H.
Saeki, T. Katsuki, and M. Yamaguchi, Bull. Chem. Soc. Jpn.,
52, 1989 (1979).
DMAP (0.02 equiv.) Hf(OTf)4 (0.15 equiv.)
toluene, rt, 15 min.
(1.0 equiv.)
R = Ph(CH2)2
Entry
R0OH
Time ( )a /h
Yield ( )a /%
1
2
3
4
5
6
Ph(CH2)3OH
0.5 (4)
1 (4)
2 (4)
1 (4)
1 (4)
1 (4)
90 (66)
84 (28)
85 (9)
Ph(CH2)2CH(OH)CH3
c-C6H11OH
3
4
5
Di(2-pyridyl) carbonate (DPC): S. Kim, J. I. Lee, and Y. K. Ko,
Tetrahedron Lett., 25, 4943 (1984).
i-Pr2CHOH
91 (53)
93 (77)
90 (16)
t-BuMeCHOH
(-)-MenthylOH
O,O0-Di(2-pyridyl) thiocarbonate (DPTC): K. Saitoh, I. Shiina,
and T. Mukaiyama, Chem. Lett., 1998, 679.
aValues in parentheses are those obtained in CH3CN by using 0.15 equivalents
of I2 instead of Hf(OTf)4.
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).
4-(Trifluoromethyl)benzoic anhydride: I. Shiina, S. 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).
Next, esterification of carboxylic acids with alcohols using
2-DTC was tried in the presence of catalytic amounts of DMAP
and Hf(OTf)4.12 The esterification of 3-phenylpropionic acid
with various alcohols including bulky secondary ones proceeded
smoothly to afford the corresponding esters in high yields
(Table 2, Entries 1–6). It is noted that the above reactions using
a catalytic amount of Hf(OTf)4 proceeded smoothly though the
same reactions did not proceed effectively when a catalytic
amount of iodine was used.
6
7
8
4-Nitrobenzoic anhydride/Sc(OTf)3: K. Ishihara, M. Kubota,
H. Kurihara, and H. Yamamoto, J. Org. Chem., 61, 4560
(1996).
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, 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).
Table 3. Esterification using various carboxylic acids and
alcohols
O
O
2-DTC (1.0 equiv.)
R'OH (1.2 equiv.)
R
OH
R
OR'
Hf(OTf)4 (0.15 equiv.)
DMAP (0.02 equiv.)
toluene, rt, 15 min.
(1.0 equiv.)
Entry
RCO2H
R0OH
Time/h Yield/%
59a
1
2
3
4
5
6
7
8
Ph(CH2)2COOH
Ph(CH2)2COOH
CH2=CHCH2OH
CH2=CHCH2OH
2
1
94
(E)-EtCH=CHCH2COOH Ph(CH2)3OH
(E)-EtCH=CHCH2COOH Ph(CH2)3OH
0.5
0.5
0.5
0.5
0.5
0.5
76a
89
c-C6H11COOH
c-C6H11COOH
Me3CCOOH
Me3CCOOH
Ph(CH2)2CH(OH)CH3
94
c-C6H11OH
86
Ph(CH2)3OH
94b
80b,c
Ph(CH2)2CH(OH)CH3
aReaction was performed by using 0.05 equivalents of DMAP and 1.05 equiva-
lents of I2 in CH3CN. bSynthesis of 2-thienylester was completed within 1 h.
cDMAP (0.05 equivalents) and Hf(OTf)4 (0.35 equivalents) in toluene (0.2 mL)
were used.
9
T. Mukaiyama, Y. Oohashi, and K. Fukumoto, Chem. Lett., 33,
552 (2004).
10 Y. Oohashi, K. Fukumoto, and T. Mukaiyama, Chem. Lett., 33,
968 (2004).
11 I. Hachiya, M. Moriwaki, and S. Kobayashi, Bull. Chem. Soc.
Jpn., 68, 2053 (1995); S. Kobayashi, M. Moriwaki, and I.
Hachiya, Bull. Chem. Soc. Jpn., 70, 267 (1997); S. Kobayashi,
S. Iwamoto, and S. Nagayama, Synlett, 1997, 1099.
Finally, this esterification between various carboxylic acids
and alcohols was tried (Table 3). The corresponding ester was
obtained in high yield when allyl alcohol was used, whereas
the use of 1.05 equivalents of iodine instead of 0.15 equivalents
of Hf(OTf)4 gave the desired product in 59% yield along with a
by-product formed by the addition of iodine to olefinic bond of
the resulted product (Entries 1, 2). Also, the desired ester was
obtained in high yield when hexenoic acid was used but the yield
of the desired product decreased to 76% when 1.05 equivalents
of iodine was used (Entry 3, 4). The corresponding esters were
also obtained in good to high yields in the case of using hindered
ꢀ,ꢀ-disubstituted carboxylic acid and pivalic acid (Entries 5–8).
It is noted that an efficient method for the synthesis of var-
ious esters by using nearly equimolar amounts of free carboxylic
acids, alcohols and 2-DTC in the presence of catalytic amounts
of DMAP and Hf(OTf)4 was established.
12 A typical experimental procedure was as follows: to a mixture
of 3-phenylpropionic acid (26.5 mg, 0.176 mmol) and 2-DTC
(40.0 mg, 0.176 mmol) in toluene (0.4 mL) was added DMAP
(0.43 mg, 0.0035 mmol). After stirring for 15 min at room
temperature, 3-phenyl-1-propanol (28.8 mg, 0.211 mmol) and
then a solution of Hf(OTf)4 (20.5 mg, 0.027 mmol) in CH3CN
(0.05 mL) was added. The reaction mixture was stirred for
30 min at room temperature and then saturated aqueous sodium
hydrogencarbonate was added. The mixture was extracted with
ether, 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 layer chromatography to afford the corre-
sponding ester (42.8 mg, 90%) as a colorless oil.
This study was supported in part by a Grant of the 21st
Published on the web (Advance View) January 15, 2005; DOI 10.1246/cl.2005.190