Catalytic Enantioselective Iodocyclization of γ-Hydroxy-cis-alkenes

Full text of DOI:10.1021/ja0369921

Published on Web 12/02/2003
Catalytic Enantioselective Iodocyclization of γ-Hydroxy-cis-alkenes
Sung Ho Kang,* Sung Bae Lee, and Chul Min Park
Center for Molecular Design and Synthesis, Department of Chemistry, School of Molecular Science (BK21),
Korea AdVanced Institute of Science and Technology, Daejeon 305-701, Korea
Received July 1, 2003; E-mail: shkang@kaist.ac.kr
Table 1. Iodocyclization of 6 Using (R,R)-Salen-M Complexes
1-5
Electrophile-promoted cyclizations belong to one of the most
frequently practiced organic transformations in heterocyclic chem-
istry, which can be extended to the useful functionalization of
olefinic double bonds.1 Although extensive efforts have been made
to explore these cycloadditions under a variety of conditions, their
enantioselective version has been rarely investigated. The stereo-
selective electrophile-mediated cyclizations have been mostly
limited to the substrate-controlled intramolecular cyclization.2 In
recent years, chiral selenium reagents have been designed to
consummate the asymmetric reagent-controlled intramolecular
selenocyclization, albeit relatively impractically.3 Other reported
asymmetric cycloadditions have been implemented through iodo-
lactonization with iodonium ion-chiral amine complexes,4 iodo-
cyclization of bidentate substrates with iodine in the presence of
chiral Ti(IV) alkoxide,5 chlorohydroxylation with Pd(II)-BINAP
complex,6 and oxymercuration with chiral Hg(II) carboxylates7 or
Hg(II)-bisoxazoline complexes.8 It is challenging to devise chiral
electrophiles comprising especially halonium and Hg(II) cations.
Furthermore, the reagents are usually required in excess amounts
to complete corresponding iodocyclizations. Therefore, it is of
great value and significance to develop catalytic asymmetric iodo-
cyclization. In this communication, we report our interim results
of catalytic enantioselective intramolecular iodoetherification of
γ-hydroxy-cis-alkenes using chiral salen-Co complexes to form
2-substituted tetrahydrofurans.
c
entry
(R,R)-salen−M (equiv)
% yield
%eed,e
1b
2
3
4
5
6
7
8
9
-
32 (63)
13 (84)
82
-
0
0
1 (1.0)
1 (0.2)
2 (1.0)
2 (0.2)
3 (1.0)
3 (0.2)
4 (1.0)
4 (0.2)
5 (1.0)
5 (0.2)
57 (37)
19 (58)
44 (47)
43 (37)
57 (42)
25 (74)
44 (47)
41 (53)
20 (2S,6S)
7 (2S,6S)
42 (2R,6R)
21 (2R,6R)
60 (2R,6R)
29 (2R,6R)
20 (2R,6R)
4 (2R,6R)
10
11
a [6] ) 15.8 mM. b The iodocyclization was carried out with 1.2 equiv
of I2. c Percentage of recovered sm in parentheses. d Determined by HPLC
analysis using DAICEL OD-H. e For determination of absolute configura-
tion, see Supporting Information.
To effect our proposed asymmetric iodocyclization, it is impera-
tive to impose a chiral environment around the iodonium cation,
which should be transmitted to substrate ultimately. Besides, the
generated chiral iodonium reagent should be more activated to
secure higher enantioselectivity by suppressing background cy-
clization in a relative sense. After screening various combination
of iodonium reagents, and Lewis acids or bases as activators as
well as chirality providers, iodine and salen-metal complex couples
were found promising. Representative examples are described in
Table 1. In the absence of the complexes, iodocyclization of 6
progressed to some extent (entry 1). While the highest enantio-
selectivity was acquired with 1.0 equiv of (R,R)-salen-CrCl
complex 4,9 no stereoselectivity was observed with (R,R)-salen-
Co complex 110 (entries 2, 3, and 8). It is noted that the major
product with (R,R)-salen-FeCl complex 211 is enantiomeric to those
with the remaining complexes (entries 4 and 5).10,12 Since the
cyclization was driven to completion using only 1 catalytically
rather than in a stoichiometric amount (entries 2 and 3), (R,R)-
salen-Co complex 1 was chosen as the seeking Lewis acid.
Amelioration of the stereochemical reactivity of 1 was pursued
with several additives.13 The results are displayed in Table 2, where
it can be seen that there is considerable enhancement of enantio-
selectivity with NCS but no effect with NIS (entries 3-5). Toluene
turned out to be an even better solvent than CH2Cl2, probably in
part due to the reduced background reaction in the former (entry
6). Optimization of the iodocyclization was elaborated by adjusting
Table 2. Iodocyclization of 6 Using (R,R)-Salen-Co(II) Complex 1
with Additivesa
entry
additive
solvent
% yieldd
%ee
1
2
3
4
Ph3PO
4-PPNOc
NCS
NCS
NIS
-
NCS
CH2Cl2
CH2Cl2
CH2Cl2
PhMe
PhMe
PhMe
60 (21)
57 (26)
70 (16)
73 (11)
32 (47)
16 (79)
89
5
0
50
76
0
-
83
5
6e
7f
PhMe
a 0.2 equiv of 1, 0.4 equiv of additive and 1.2 equiv of I2 were used.
b [6] ) 15.8 mM. c 4-PPNO ) 4-phenylpyridine N-oxide. d Percentage of
recovered sm in parentheses. e Iodocyclization was carried out without 1.
f 0.3 equiv of 1, 0.75 equiv of NCS and 1.2 equiv of I2 were used.
the relative amounts of the involved reagents. The most salient
iodoetherification was achieved with 1.2 equiv of I2 in the presence
of 0.3 equiv of 1 and 0.75 equiv of NCS in toluene (entry 7). It
was found that the longer mixing time of 1 and NCS degenerated
the stereoselectivity. The amount of iodine needed was determined
by the optimal compromise between the minimal background
reaction and the maximum conversion. Further improvement of the
stereoselectivity was explored by examining concentration effect.
Among the examined concentrations (31.6, 15.8, 10.5, 7.9, 5.3 mM),
9
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J. AM. CHEM. SOC. 2003, 125, 15748-15749
10.1021/ja0369921 CCC: $25.00 © 2003 American Chemical Society

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
(1) (a) Rousseau, G.; Robin, S. Tetrahedron 1998, 54, 13681. (b) Harding,
K. E.; Tinger, T. H. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, p 463. (c) Mulzer,
J. In Organic Synthesis Highlights; Mulzer, J., Altenbach, H. J., Braun,
M., Krohn, K., Reissig, H. U., Eds.; VCH: Weinheim, 1991; p 157.
(2) (a) Fuji, K.; Node, M.; Naniwa, Y.; Kawabata, T. Tetrahedron Lett. 1990,
31, 3175. (b) Furth, M. J.; Brown, E. G. J. Am. Chem. Soc. 1987, 109,
6844.
(3) (a) Back, T. G.; Dyck, B. P.; Nan, S. Tetrahedron 1999, 55, 3191. (b)
Nishibayashi, Y.; Srivastava, S. K.; Takada, H.; Fukuzawa, S.-I.; Uemura,
S. J. Chem. Soc., Chem. Commun. 1995, 2321. (c) Wirth, T. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1726. (d) Fujita, K.-I.; Iwaoka, M.;
Tomoda, S. Chem. Lett. 1992, 1123.
(4) (a) Haas, J.; Piguel, S.; Wirth, T. Org. Lett. 2002, 4, 297. (b) Grossman,
R. B.; Trupp, R. J. Can. J. Chem. 1998, 76, 1233.
(5) (a) Kitagawa, O.; Taguchi, T. Synlett 1999, 1191. (b) Kitagawa, O.;
Hanano, T.; Tanabe, K.; Shiro, M.; Taguchi, T. J. Chem, Soc., Chem.
Commun. 1992, 1005.
(6) (a) El-Qisairi, A. K.; Hamed, O.; Henry, P. M. J. Org. Chem. 1998, 63,
2790. (b) El-Qisairi; A. K.; Qaseer, H. A.; Katsigras, G.; Lorenzi, P.;
Trivedi, U.; Tracz, S.; Hartman, A.; Miller, J. A.; Henry, P. M. Org. Lett.
2003, 5, 439.
(7) (a) Grundon, M. F.; Stewart, D.; Watts, W. E. J. Chem. Soc., Chem.
Commun. 1973, 573. (b) Carlson, R. M.; Funk, A. H. Tetrahedron Lett.
1971, 3661.
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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