LETTER
Iodolactonizations of 4-Pentenoic Acid Derivatives
2293
I+ source at –18 °C. Under these conditions, a range of to increase the ee value (entry 6). In fact, similar influence
substrates having various substituents such as sterically has also been noted for some analogous 4-substituted 4-
bulky, electron-rich and electron-deficient, and aromatic pentenoic acids, and is attributed probably to the different
and aliphatic groups13 (4a–f) were investigated. As shown stability of the intermediate iodonium ion as affected by
in Table 4, in most cases, good enantioselectivities paired the electronic property of the substituents.6a
with high yield were obtained for a diverse class of sub-
In conclusion, we have developed a new reagent-con-
strates, indicating that this protocol is amenable to a broad
trolled protocol for stereoselective iodolactonization by
range of substances.14 Of particularly interest is that the
using catalytical amount of chiral salen–Co(II) complex
as Lewis acid. This protocol is shown to be efficient and
applicable to a range of substrates, providing iodolactones
substrate 4f, whose structure is substituted by a small ali-
phatic methyl group, also exhibited a fairly good selectiv-
ity with an ee value of 55% (entry 7). This result is in
with high yield as well as good selectivity. The ee values
sharp contrast to the other reagent-controlled asymmetric
of the obtained lactones are at least 20% higher when
iodolactonizations where substitution of the substrates by
compared to the reported data for substrates 2 and 4a.6a
Most interestingly, the salen–Co(II) complex exhibited
also fairly good selectivity to the 4-methyl-4-pentenoic
an aliphatic group such as methyl and isopropyl substitu-
ents virtually produced lactones in racemic form.6a,7 Final-
ly, it should be mentioned that the electronic nature of the
substituent affects notably the outcome of the lactoniza-
acid 4f (ee = 55%), in sharp contrast to the racemic form
as appeared in previous reports.6a,7 Consequently, the
tion reactions. For instance, by introducing an electron-
method presented in this work is believed to be highly po-
rich OMe group into the phenyl ring (4d), the selectivity
tential for the stereoselective construction of halolactone
of the cyclization was markedly decreased (entry 5).
derivatives. Further work towards the development of a
However, an electron-deficient Br instead of OMe tends
more effective salen–Co system by modifying the salen
ligands, for instance, introducing electronic and steric ef-
fects, and the application of the system to a broader range
of substrates is currently under way.
Table 4 Iodolactonizations of Substituted 4-Pentenoic Acid Using
the Optimized Conditionsa
O
O
1. 1a, NCS, toluene, r.t., 0.5 h
I
R
R
COOH
Supporting Information for this article is available online at
2. I2, –18 °C, 20 h
4
5
a
b
References and Notes
(1) For recent reviews, see: (a) Dowle, M. D.; Davies, D. I.
Chem. Soc. Rev. 1979, 8, 171. (b) Rousseau, G.; Robin, S.
Tetrahedron 1998, 54, 13681.
(2) (a) Hauske, J. R.; Julin, S. M. Tetrahedron Lett. 1993, 34,
4909. (b) Jung, M.; Ham, J.; Song, J. Org. Lett. 2002, 4,
2763. (c) Kim, S.; Ko, H.; Kim, E.; Kim, D. Org. Lett. 2002,
4, 1343. (d) Janecki, T.; Błaszczyk, E.; Studzian, K.;
Janecka, A.; Krajewska, U.; Różalski, M. J. Med. Chem.
2005, 48, 3516.
(3) (a) Jiang, X. P.; Fu, C. L.; Ma, S. M. Chem. Eur. J. 2008, 14,
9656. (b) Jin, L.; Nemoto, T.; Nakamura, H.; Hamada, Y.
Tetrahedron: Asymmetry 2008, 19, 1106. (c) Moon, H. S.;
Eisenberg, S. W. E.; Wilson, M. E.; Schore, N. E.; Kurth,
M. J. J. Org. Chem. 1994, 59, 6504. (d) Monache, G. D.;
Misiti, D.; Salvatore, P.; Zappia, G. Tetrahedron:
Asymmetry 2000, 11, 1137.
d
f
MeO
c
e
Me
Br
Entry
Substrate
Product
315
5a
Yield (%)b ee (%)c
1
2
3
4
5
6
7
2
87
93
92
86
89
72
73
67
70
71
83
22
73
55d
4a
4b
4c
4d
4e
4f
5b
5c
(4) Kitagawa, O.; Hanano, T.; Tanabe, K.; Shiro, M.; Taguchi,
5d
T. J. Chem. Soc., Chem. Commun. 1992, 1005.
5e
(5) Cui, X. L.; Brown, R. S. J. Org. Chem. 2000, 65, 5653.
(6) (a) Haas, J.; Piguel, S.; Wirth, T. Org. Lett. 2002, 4, 297.
(b) Haas, J.; Bissmire, S.; Wirth, T. Chem. Eur. J. 2005, 11,
5777. (c) Garnier, J. M.; Robin, S.; Rousseau, G. Eur. J.
Org. Chem. 2007, 3281.
(7) (a) Wang, M.; Gao, L. X.; Yue, W.; Mai, W. P. Synth.
Commun. 2004, 34, 1023. (b) Wang, M.; Gao, L. X.; Mai,
W. P.; Xia, A. X.; Wang, F.; Zhang, S. B. J. Org. Chem.
2004, 69, 2874. (c) Grossman, R. B.; Trupp, R. J. Can. J.
Chem. 1998, 76, 1233.
5f
a Reactions were carried out using 1a (0.068 mmol), NCS (0.043
mmol), I2 (0.238 mmol), and substrate (0.170 mmol) in toluene (8
mL).
b Isolated yield.
c Determined by HPLC analysis using DAICEL OD-H.
d Determined by GC analysis using CHIRASIL-DEX CB.
Synlett 2009, No. 14, 2291–2294 © Thieme Stuttgart · New York