Chemistry Letters Vol.34, No.5 (2005)
711
Table 2. Lactonization of 12-hydroxydodecanoic acid by using
2-DTC promoted by DMAP and several Lewis acids
pressed in comparison with the results obtained by carrying
out the same reaction under previously reported conditions of us-
ing iodine.11 Further, it is noted that this reaction provides an ex-
cellent method for the synthesis of 10-, 11-membered ring lac-
tones which were known to be difficult by conventional methods.
It is also noted that this is effective from the point of view that
amounts of the reagent decreased (1equiv. of 2-DTC) and reac-
tion time became shorter (6 h) compared with Yamamoto’s
method which used 2 equiv. of coupling reagent and the reaction
time for 6–20 h.
2-DTC
Lewis acid
(10 mol%)
O
O
O
O
(1.0 equiv.)
10
O
+
O
HO
OH
DMAP
(5 mol%)
CH CN, rt, 15 min. 6 h
toluene
(2 mM)
10
10
Lactone
10
O
1
Diolide
(1.0 equiv.)
3
Entry Lewis acid Yielda/% Entry Lewis acid
Yielda/%
1
2
3
4
5
6
7
8
BF3-OEt2 N.D. (N.D.)
9
N.D. (N.D.) 10 HfCl4
Yb(OTf)3
N.D. (N.D.)
N.D. (N.D.)
TiCl4
SnCl4
Mg(OTf)2 N.D. (N.D.) 12 HfCl(OTf)3 83
b
N.D. (N.D.) 11 HfCl2(OTf)2 41
(N.D.)
(<11)
(3)
c
It is noted that an effective method for the synthesis of var-
ious macrolactones was established by using equimolar amounts
of !-hydroxycarboxylic acids and 2-DTC in the presence of a
catalytic amount of DMAP and Hf(OTf)4. Other group 4 metal
triflates such as Ti(OTf)4 and Zr(OTf)4 were also effective for
this lactonization.
Cu(OTf)2 30
Sc(OTf)3 57
La(OTf)3 N.D. (N.D.) 15 Zr(OTf)4
(trace) 13 Hf(OTf)4
86
82
84
d
(trace) 14 Ti(OTf)4
(<9)
(<2)
d
Gd(OTf)3 trace (N.D.)
A solution of 2-thienyl 12-hydroxydodecanoate derived from 1 and
2-DTC in CH3CN (10 mL) was slowly added to a solution of Lewis
acid in toluene (78 mL) at 100 ꢁC. aIsolated yield of lactone
This study was supported in part by a Grant of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan.
b
(diolide). Generated in situ from 1 equiv. of MCl4 and 2 equiv. of
AgOTf. cGenerated in situ from 1 equiv. of MCl4 and 3 equiv. of
AgOTf. dGenerated in situ from 1 equiv. of MCl4 and 4 equiv. of
AgOTf.
References and Notes
1
2
DCC: E. P. Boden and G. E. Keck, J. Org. Chem., 50, 2394 (1985).
2,4,6-Trichlorobenzoyl chloride: J. Inanaga, K. Hirata, H. Saeki, T.
Katsuki, and M. Yamaguchi, Bull. Chem. Soc. Jpn., 52, 1989 (1979).
2,20-dipyridyl disulfide/Ph3P: E. J. Corey and K. C. Nicolaou, J. Am.
Chem. Soc., 96, 5614 (1974).
1-Alkyl-2-halopyridinium salts/Et3N: T. Mukaiyama, M. Usui, and
K. Saigo, Chem. Lett., 1976, 49.
2-Me-6-NO2-benzoic anhydride (MNBA): I. Shiina, M. Kubota, H.
Oshiumi, and M. Hashizume, J. Org. Chem., 69, 1822 (2004).
DEAD/Ph3P: T. Kurihara, Y. Nakajima, and O. Mitsunobu, Tetra-
hedron Lett., 28, 2455 (1976).
Table 3. Lactonization of various !-hydroxycarboxylic acids
by using 2-DTC promoted by DMAP and Hf(OTf)4
3
4
5
6
7
8
9
Hf(OTf)4
(10 mol%)
O
2-DTC
(1.0 equiv.)
O
n
O
O
n
O
+
O
HO
OH
DMAP
(5 mol%)
CH3CN,
toluene
n
n
O
100oC
lactone
diolide
(1.0 equiv.)
slow addition
for 5 h
rt, 15 min.
Yielda ( )b/%
Diolide
trace (<25)
(30)
4-(Trifluoromethyl)benzoic anhydride: I. Shiina, Tetrahedron, 60,
1587 (2004).
Entry
n (ring size)
Lactone
4-Nitrobenzoic anhydride/Sc(OTf)3: K. Ishihara, M. Kubota, H.
Kurihara, and H. Yamamoto, J. Org. Chem., 61, 4560 (1996).
K. Venkataraman and D. R. Wagle, Tetrahedron Lett., 21, 1893
(1980); E. J. Corey and D. J. Brunelle, Tetrahedron Lett., 28,
3409 (1976); J. Otera, T. Yano, Y. Himeno, and H. Nozaki,
Tetrahedron Lett., 27, 4501 (1986).
1
2
3
7 (10)
8 (11)
9 (12)
53
70
78
(trace)
(23)
(58)
5
<9 (18)
4
5
6
7
8
10 (13)
11 (14)
12 (15)
13 (16)
14 (17)
b
89c (77)
<7 (14)
<2 (<8)
<6 (<11)
<1 (<6)
<3 (<7)
89
94
92
91
(85)
(87)
(90)
(92)
10 C. A. Dvorak, W. D. Schmitz, D. J. Poon, D. C. Pryde, J. P. Lawson,
R. A. Amos, and A. I. Meyers, Angew. Chem., Int. Ed., 39, 1664
(2000).
11 Y. Oohashi, K. Fukumoto, and T. Mukaiyama, Chem. Lett., 34, 72
(2005).
12 Y. Oohashi, K. Fukumoto, and T. Mukaiyama, Chem. Lett., 34, 190
(2005).
13 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).
14 A typical experimental procedure was as follows: 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). After stirring for 15 min at rt, the resultant
solution was slowly added to solution of Hf(OTf)4 (13.7 mg,
0.0176 mmol) in toluene (78 mL) at 100 ꢁC for 5 h and then reaction
mixture was stirred for 1 h. The resultant solution was cooled to
room temperature and was evaporated the solvent. The mixture
was diluted in ether and was added saturated aqueous sodium hydro-
gen carbonate under ice cooling. 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 corresponding lactone (30.0
mg, 86%).
aIsolated yield. Values in parentheses are those obtained previ-
ously by using 2–4 equiv. of iodine instead of Hf(OTf)4.12 cReflux
temperature.
cated that group 4 metal triflates exhibit unique characteristic
properties of promoting this 2-DTC mediated lactonization.
Results of the lactonization using various !-hydroxycarbox-
ylic acids are listed in Table 3.14 Thirteen to seventeen mem-
bered ring lactones were obtained in high yields (Entries 4–8)
and the desired product was similarly obtained in 78% yield
when 11-hydroxyundecanoic acid was used (Entry 3). Eleven
membered ring lactone was also obtained in 70% yield when
the cyclization was carried out by using the corresponding 10-
hydroxydecanoic acid (Entry 2). Although, preparation of 10-
membered ring lactone was known to be difficult, the desired
lactone was obtained in 53% yield (Entry 1). It is noted that
the corresponding lactones were obtained in higher yields and
formation of the undesired corresponding diolides was sup-
Published on the web (Advance View) April 16, 2005; DOI 10.1246/cl.2005.710