C O M M U N I C A T I O N S
Table 3. Iodocyclization of 6 Using (R,R)-Salen-Co(III)
in one portion reduced the enantioselectivity by a few percent ee.
Since a little discrepancy could be surmounted by dropwise addition
of 6 over 8 h, the method was also applied to the others. The
experimental data shown in Table 4 reveal that remarkable
enantioselectivity was realized with most of the substrates, although
somewhat lower asymmetric induction was observed with the
sterically least demanding methylalkene 9 and the branched
isopropylalkene 12 (entries 3 and 6).19
In conclusion, we have developed a highly enantioselective
iodocyclization of γ-hydroxy-cis-alkenes by unprecedented use of
the catalyst system derived from (R,R)-salen-Co(II) complex and
NCS to procure 2-substituted tetrahydrofurans up to 90% ee, which,
to the best of our knowledge, is the highest reported value in the
related iodocyclizations.
Complexesa
entry
HX
% yield
% ee
1
2
3
4
5
-
89
86
89
79
82
86
40
71
76
84
PhCO2H
2,4,6-Me3C6H2CO2H
C6F5OH
(CF3)3COH
a 0.3 equiv of 1, 0.3 equiv of HX, 0.75 equiv of NCS and 1.2 equiv of
I2 were used. b [6] ) 10.5 mM.
Table 4. Iodocyclization Using (R,R)-Salen-Co(II) 1 with NCSa,b
Acknowledgment. This work was supported by CMDS, Cre-
ative Research Initiatives of the Korean Ministry of Science and
Technology, and the Brain Korea 21 Project.
Supporting Information Available: Experimental details (PDF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
References
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c
entry
substrate
product
% yield
% ee
1
2
3
4
5
6
7
6
8
9
10
11
12
13
(R)-7
14
15
16
17
18
19
94
94
96
89
85
83
89
86
84d
67e,f
82e,f
85e
73e
90g
a 0.3 equiv of 1, 0.75 equiv of NCS and 1.2 equiv of I2 were used.
b Substrate was added over 8 h using a syringe pump. c For determination
of absolute configuration, see Supporting Information. d Determined by
HPLC analysis of reductively deiodinated product of 14 using Regis Welk-
O1 (R,R). e Determined by GC analysis using CHIRALDEX B-DM. f The
absolute configuration was not determined. g Determined by HPLC analysis
of 20 using DAICEL OD.
the highest enantioselectivity was attained with 10.5 mM concentra-
tion of 6.14
More acidic (R,R)-salen-Co(III) complexes, which are specu-
latively formed from (R,R)-salen-Co(II) complex and NCS, were
generated in situ from 1 with protic oxidants to explore their
effectiveness on the asymmetric iodocyclization.15 The cyclization
was carried out using the complexes under the optimized reaction
conditions, and the outcomes are reported in Table 3. Although
the complexes prepared with 2,4,6-trimethylbenzoic acid, penta-
fluorophenol, and perfluoro-tert-butyl alcohol delivered good
asymmetric induction, none of them was superior to 1 (entries 1
and 3-5).16 Since (R)-7 was produced in 11% yield and 35% ee
using perfluoro-tert-butyl alcohol without NCS, NCS proved to be
the essential additive. In a related experiment using (R,R)-salen-
Co(III)Cl,17 (R)-7 was afforded in 79% ee but only 35% yield. In
addition, the salen structure was varied by switching the two C5-
and C5′-tert-butyl groups with chloro, tert-butoxy, phenyl, methyl,
and 2,4,6-trimethylbenzyloxy groups.18 Among the corresponding
(R,R)-salen-Co(II) complexes, the etherification was completed
with only methylsalen-Co(II) complex to give (R)-7 in 83% yield
and 47% ee. While little stereoselectivity was elicited with
chlorosalen-Co(II) complex, the highest 57% ee was engendered
with 2,4,6-trimethylbenzyloxysalen-Co(II) complex.
(8) Kang, S. H.; Kim, M. J. Am. Chem. Soc. 2003, 125, 4684.
(9) Mart´ınez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am.
Chem. Soc. 1995, 117, 5891.
(10) Leung, W.-H.; Chan, E. Y. Y.; Chow, E. K. F.; Williams, I. D.; Deng,
S.-M. J. Chem. Soc., Dalton Trans. 1996, 1229.
(11) Fu¨rstner, A.; Leitner, A.; Me´ndez, M.; Krause, H. J. Am. Chem. Soc. 2002,
124, 13856.
(12) Larrow, J. F.; Jacobsen, E. N.; Gao, Y.; Hong, Y.; Nie, X.; Zepp, C. M.
J. Org. Chem. 1994, 59, 1939.
(13) (a) Vogl, E. M.; Gro¨ger, H.; Shibasaki, M. Angew. Chem., Int. Ed. 1999,
38, 1570. (b) Jacobsen, E. N.; Kakiuchi, F.; Konsler, R. G.; Larrow, J.
F.; Tokunaga, M. Tetrahedron Lett. 1997, 38, 773.
(14) Iodocyclization of the corresponding E-isomer under the established
conditions proceeded with poor enatioselectivity and moderate chemical
conversion (11% ee and 50% yield).
(15) (a) Ready, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 6086. (b)
Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997,
277, 936. (c) Jacobsen, E. N.; Kakiuchi, F.; Konsler, R. G.; Larrow, J. F.;
Tokunaga, M. Tetrahedron Lett. 1997, 38, 773.
(16) To investigate the possible involvement of HCl in the cyclization, which
might be generated in situ, iodocyclization of 6 was carried out using
0.15 equiv of NCS and 0.6 equiv of HCl instead of 0.75 equiv of NCS to
provide (R)-7 in 81% ee and 39% yield.
(17) The preparation method of (R,R)-salen-Co(III)Cl was gratefully provided
by Mr. Sang Kyun Kim from Prof. Jacobsen’s group at Harvard University.
Hong, J. Ph.D. Thesis, Harvard University, Cambridge, Massachusetts,
2001.
(18) (a) Ready, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 2687. (b)
Palucki, M.; Finney, N. S.; Pospisil, P. J.; Gu¨ler, M. L.; Ishida, T.;
Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120, 948.
Iodocyclization of various γ-hydroxy-cis-alkenes 6-13 was
conducted under the optimized conditions. When the reaction scale
increased from 0.1 to 0.4 mmol, addition of the model substrate 6
(19) Iodocyclization of 6 was scaled up to 2.6 mmol with comparable
enantioselectivity and chemical yield (85% ee and 89% yield).
JA0369921
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J. AM. CHEM. SOC. VOL. 125, NO. 51, 2003 15749