Enantioselective bromocyclization of olefins catalyzed by chiral phosphoric acid

Article abstract of DOI:10.1021/ol202527g

A chiral phosphoric acid catalyzed enantioselective bromocyclization of olefins is described. Various cis-, trans-, or trisubstituted ?-hydroxyalkenes and γ-amino-alkenes can cyclize under the reaction conditions to give optically active 2-substituted tetrahydrofurans and tetrahydropyrroles in up to 91% ee.

Full text of DOI:10.1021/ol202527g

ORGANIC
LETTERS
2011
Vol. 13, No. 24
6350–6353
Enantioselective Bromocyclization of
Olefins Catalyzed by Chiral Phosphoric
Acid
Deshun Huang,† Haining Wang,† Fazhen Xue,† Huan Guan,† Lijun Li,† Xianyou Peng,†
and Yian Shi*,†,‡
Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular
Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing
100190, China, and Department of Chemistry, Colorado State University, Fort Collins,
Colorado 80523, United States
yian@lamar.colostate.edu
Received September 24, 2011
ABSTRACT
A chiral phosphoric acid catalyzed enantioselective bromocyclization of olefins is described. Various cis-, trans-, or trisubstituted γ-hydroxy-
alkenes and γ-amino-alkenes can cyclize under the reaction conditions to give optically active 2-substituted tetrahydrofurans and
tetrahydropyrroles in up to 91% ee.
Halogenation of olefins provides an effective approach
to introduce two heteroatoms onto CꢀC double bonds.1
In recent years, asymmetric halogenations have received
considerable attention from chemists and significant pro-
gress has been made in this area.2 A number of reagent-
controlled enantioselective halogenations of olefins have
been developed using chiral Lewis acids,3,4 chiral amines,5ꢀ7
or chiral sulfides.8 A variety of catalytic systems have also
been established with chiral Lewis acids,9ꢀ12 chiral
amines,13ꢀ17 or chiral Pd(II) complexes18 as the catalyst.
As part of our general interest in functionalization of
(4) For a leading reference on reagent-controlled intermolecular
enantioselective halogenation of olefins using chiral Lewis acids, see:
Snyder, S. A.; Tang, Z. Y.; Gupta, R. J. Am. Chem. Soc. 2009, 131, 5744.
(5) For leading references on reagent-controlled enantioselective
halolactonization of olefins using chiral amines, see: (a) Grossman,
R. B.; Trupp, R. J. Can. J. Chem. 1998, 76, 1233. (b) Haas, J.; Piguel, S.;
Wirth, T. Org. Lett. 2002, 4, 297. (c) Wang, M.; Gao, L. X.; Yue, W.;
Mai, W. P. Synth. Commun. 2004, 34, 1023. (d) Haas, J.; Bissmire, S.;
Wirth, T. Chem.;Eur. J. 2005, 11, 5777. (e) Garnier, J. M.; Robin, S.;
Rousseau, G. Eur. J. Org. Chem. 2007, 3281.
† Chinese Academy of Sciences.
‡ Colorado State University.
(1) For leading reviews on halogenation of olefins, see: (a) Dowle,
(6) For leading references on reagent-controlled enantioselective
fluorination of olefins using chiral amines, see: (a) Greedy, B.; Paris,
J. M.; Vidal, T.; Gouverneur, V. Angew. Chem., Int. Ed. 2003, 42, 3291.
(b) Wang, M.; Wang, B. M.; Shi, L.; Tu, Y. Q.; Fan, C. A.; Wang, S. H.;
Hu, X. D.; Zhang, S. Y. Chem. Commun. 2005, 5580. (c) Wilkinson, S. C.;
Lozano, O.; Schuler, M.; Pacheco, M. C.; Salmon, R.; Gouverneur, V.
Angew. Chem., Int. Ed. 2009, 48, 7083.
(7) For a leading reference on reagent-controlled enantioselective
halocyclization of polyprenoids using chiral phosphoramidites, see:
Sakakura, A.; Ukai, A.; Ishihara, K. Nature 2007, 445, 900.
(8) For a leading reference on reagent-controlled enantioselective
intermolecular halogenation of olefins using chiral sulfides, see: Snyder,
S. A.; Treitler, D. S.; Brucks, A. P. J. Am. Chem. Soc. 2010, 132, 14303.
(9) For leading references on Lewis acid catalyzed enantioselective
iodocarbocyclization, see: (a) Inoue, T.; Kitagawa, O.; Ochiai, O.; Shiro,
M.; Taguchi, T. Tetrahedron Lett. 1995, 36, 9333. (b) Inoue, T.;
Kitagawa, O.; Saito, A.; Taguchi, T. J. Org. Chem. 1997, 62, 7384.
M. D.; Davies, D. I. Chem. Soc. Rev. 1979, 8, 171. (b) Rodriguez, J.;
Dulcere, J.-P. Synthesis 1993, 1177. (c) Kitagawa, O.; Taguchi, T. Synlett
ꢀ
1999, 1191. (d) Ranganathan, S.; Muraleedharan, K. M.; Vaish, N. K.;
Jayaraman, N. Tetrahedron 2004, 60, 5273. (e) Li, G.; Kotti, S. R. S. S.;
~
ꢁ
Timmons, C. Eur. J. Org. Chem. 2007, 2745. (f) Rodrıguez, F.; Fananas,
F. J. In Handbook of Cyclization Reactions; Ma, S., Ed.; Wiley-VCH:
New York, 2010; Vol. 4, pp 951ꢀ990.
(2) For leading reviews on asymmetric halogenation of olefins, see:
(a) French, A. N.; Bissmire, S.; Wirth, T. Chem. Soc. Rev. 2004, 33, 354.
(b) Chen, G. F.; Ma, S. M. Angew. Chem., Int. Ed. 2010, 49, 2. (c)
Castellanos, A.; Fletcher, S. P. Chem.;Eur. J. 2011, 17, 5766. (d) Tan,
C. K.; Zhou, L.; Yeung, Y.-Y. Synlett 2011, 1335.
(3) For leading references on reagent-controlled enantioselective
halocyclization using chiral Lewis acids, see: (a) Kitagawa, O.; Hanano,
T.; Tanabe, K.; Shiro, M.; Taguchi, T. J. Chem. Soc., Chem. Commun.
1992, 1005. (b) Inoue, T.; Kitagawa, O.; Kurumizawa, S.; Ochiai, O.;
Taguchi, T. Tetrahedron Lett. 1995, 36, 1479.
r
10.1021/ol202527g
Published on Web 11/17/2011
2011 American Chemical Society

olefins,19 recently we have been exploring various catalytic
electrophilic addition reactions with olefins (Scheme 1).20
Herein we wish to report our preliminary studies on chiral
phosphoric acid catalyzed bromocyclization of γ-hydroxy-
alkenes and γ-amino-alkenes.21ꢀ23
Initial studies were carried out with cis-dec-4-en-1-ol
(1a) as the substrate, NBS as the bromine source, and
BINOL-derived chiral phosphoric acid as the catalyst.
Among the catalysts examined, (S)-3,30-bis(2,4,6-triiso-
propylphenyl)-BINOL phosphoric acid (3c)24 was found
to be the most effective catalyst for both conversion
and ee (Table 1, entries 1, 2, 3). Among the solvents
screened, DCM was found to be the solvent of choice
Scheme 1
Table 1. Studies on Reaction Conditionsa
(10) For leading references on Lewis acid catalyzed enantioselective
iodoetherification, see: (a) Kang, S. H.; Lee, S. B.; Park, C. M. J. Am.
Chem. Soc. 2003, 125, 15748. (b) Kang, S. H.; Park, C. M.; Lee, S. B.;
Kang, M. K. Synlett 2004, 1279. (c) Kang, S. H.; Kang, S. Y.; Park,
C. M.; Kwon, H. Y.; Kim, M. Pure Appl. Chem. 2005, 77, 1269. (d)
Kwon, H. Y.; Park, C. M.; Lee, S. B.; Youn, J.-H.; Kang, S. H. Chem.;
Eur. J. 2008, 14, 1023.
(11) For a leading reference on Lewis acid catalyzed enantioselective
iodolactonization, see: Ning, Z. L.; Jin, R. Z.; Ding, J. Y.; Gao, L. X.
Synlett 2009, 2291.
(12) For leading references on Lewis acid catalyzed intermolecular
enantioselective halogenationof olefins, see: (a) Sakurada, I.; Yamasaki,
S.; Gottlich, R.; Iida, T.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc.
2000, 122, 1245. (b) Cai, Y. F.; Liu, X. H.; Hui, Y. H.; Jiang, J.; Wang,
W. T.; Chen, W. L.; Lin, L. L.; Feng, X. M. Angew. Chem., Int. Ed. 2010,
49, 6160. (c) Cai, Y. F.; Liu, X. H.; Jiang, J.; Chen, W. L.; Lin, L. L.;
Feng, X. M. J. Am. Chem. Soc. 2011, 133, 5636.
(13) For leading references on chiral amines catalyzed enantioselec-
tive halolactonization, see: (a) Wang, M.; Gao, L. X.; Mai, W. P.; Xia,
A. X.; Wang, F.; Zhang, S. B. J. Org. Chem. 2004, 69, 2874. (b)
Whitehead, D. C.; Yousefi, R.; Jaganathan, A.; Borhan, B. J. Am.
Chem. Soc. 2010, 132, 3298. (c) Zhou, L.; Tan, C. K.; Jiang, X.; Chen, F.;
Yeung, Y.-Y. J. Am. Chem. Soc. 2010, 132, 15474. (d) Veitch, G. E.;
Jacobsen, E. N. Angew. Chem., Int. Ed. 2010, 49, 7332. (e) Murai, K.;
Matsushita, T.; Nakamura, A.; Fukushima, S.; Shimura, M.; Fujioka,
H. Angew. Chem., Int. Ed. 2010, 49, 9174. (f) Zhang, W.; Zheng, S.; Liu,
N.; Werness, J. B.; Guzei, I. A.; Tang, W. P. J. Am. Chem. Soc. 2010, 132,
3664. (g) Yousefi, R.; Whitehead, D. C.; Mueller, J. M.; Staples, R. J.;
Borhan, B. Org. Lett. 2011, 13, 608. (h) Tan, C. K.; Zhou, L.; Yeung,
Y.-Y. Org. Lett. 2011, 13, 2738.
t
time
(h)
yield
(%)b
ee
entry
3
solvent
(°C)
(%)c
1
2
3
4
5
6
7
8
3a
3b
3c
3c
3c
3c
3c
3c
DCM
DCM
DCM
CHCl3
PhMe
DCM
DCM
DCM
ꢀ60
ꢀ60
ꢀ60
ꢀ60
ꢀ60
ꢀ30
0
48
48
48
48
48
48
18
6
83
22
77
74
45
97
97
93
10
ꢀ68d
70
57
50
75
75
rt
71
a The reaction was carried out with 1a (0.20 mmol), NBS (0.24
mmol), and 3 (0.02 mmol) in solvent (2.0 mL) unless otherwise stated.
b Isolated yield. c Determined by chiral GC analysis. d The opposite
enantiomer of product 2a was obtained.
(Table 1, entries 3, 4, 5). For the current substrate (1a) and
catalyst (3c), the reaction temperature did not have a large
impact on the enantioselectivity (Table 1, entries 3, 6, 7,
and 8). However, at higher temperature, the reaction gave
a higher yield for the product and required a shorter
(14) For leading referenceson chiral amine catalyzed enantioselective
halocyclization using amides or sulfonamides as nucleophiles, see: (a)
Jaganathan, A.; Garzan, A.; Whitehead, D. C.; Staples, R. J.; Borhan, B.
Angew. Chem., Int. Ed. 2011, 50, 2593. (b) Zhou, L.; Chen., J.; Tan,
C. K.; Yeung, Y.-Y. J. Am. Chem. Soc. 2011, 133, 9164.
(15) For leading referenceson chiral amine catalyzed enantioselective
fluorination of olefins, see: (a) Fukuzumi, T.; Shibata, N.; Sugiura, M.;
Nakamura, S.; Toru, T. J. Fluorine Chem. 2006, 127, 548. (b) Ishimaru,
T.; Shibata, N.; Horikawa, T.; Yasuda, N.; Nakamura, S.; Toru, T.;
Shiro, M. Angew. Chem., Int. Ed. 2008, 47, 4157. (c) Lozano, O.;
Blessley, G.; Martinez del Campo, T.; Thompson, A. L.; Giuffredi,
G. T.; Bettati, M.; Walker, M.; Borman, R.; Gouverneur, V. Angew.
Chem., Int. Ed. 2011, 50, 8105.
(19) (a) Shi, Y. Acc. Chem. Res. 2004, 37, 488. (b) Du, H.; Zhao, B.;
Shi, Y. J. Am. Chem. Soc. 2007, 129, 762.
(20) (a) Wang, H. N.; Huang, D. S.; Cheng, D. H.; Li, L. J.; Shi, Y.
Org. Lett. 2011, 13, 1650. (b) Huang, D. S.; Wang, H. N.; Guan, H.;
Huang, H.; Shi, Y. Org. Lett. 2011, 13, 1548.
(21) For a leading reference on desymmetrization of meso-halonium
€
ions using chiral sodium phosphate, see: Hennecke, U.; Muller, C. H.;
(16) For a leading reference on chiral amine catalyzed intermolecular
enantioselective halogenation of olefins, see: Nicolaou, K. C.; Simmons,
N. L.; Ying, Y.; Heretsch, P. M.; Chen, J. S. J. Am. Chem. Soc. 2011, 133,
8134.
€
Frohlich, R. Org. Lett. 2011, 13, 860.
(22) For leading references on Lewis acid catalyzed halogenation of
olefins, see: (a) Hajra., S.; Maji, B.; Karmakar, A. Tetrahedron Lett.
2005, 46, 8599. (b) Yeung, Y.-Y.; Gao, X.; Corey, E. J. J. Am. Chem. Soc.
2006, 128, 9644. (c) Hajra., S.; Bar, S.; Sinha, D.; Maji, B. J. Org. Chem.
2008, 73, 4320. (d) Yadav, J. S.; Subba Reddy, B. V.; Narasimha Chary,
D.; Chandrakanth, D. Tetrahedron Lett. 2009, 50, 1136.
(23) For a leading reference on studies of stability of halonium ions,
see: Denmark, S. E.; Burk, M. T.; Hoover, A. J. J. Am. Chem. Soc. 2010,
132, 1232.
(24) For leading reviews on chiral phosphoric acid catalyzed reac-
tions, see: (a) Akiyama, T. Chem. Rev. 2007, 107, 5744. (b) Terada, M.
Synthesis 2010, 1929. (c) Kampen, D.; Reisinger, C. M.; List, B. Top.
Curr. Chem. 2010, 291, 395. (d) Zamfir, A.; Schenker, S.; Freund, M.;
Tsogoeva, S. B. Org. Biomol. Chem. 2010, 8, 5262. (e) Yu, J.; Shi, F.;
Gong, L.-Z. Acc. Chem. Res. 2011, 44, 1156.
(17) For leading referenceson chiral amine catalyzed enantioselective
halogenationꢀrearrangement, see: (a) Chen, Z. M.; Zhang, Q. W.;
Chen, Z. H.; Li, H.; Tu, Y. Q.; Zhang, F. M.; Tian, J. M. J. Am. Chem.
Soc. 2011, 133, 8818. (b) Li, H.; Zhang, F. M.; Tu, Y. Q.; Zhang, Q. W.;
€
Chen, Z. M.; Chen, Z. H.; Li, J. Chem. Sci. 2011, 2, 1839. (c) Muller,
€
C. H.; Wilking, M.; Ruhlmann, A.; Wibbeling, B.; Hennecke, U. Synlett
2011, 2043.
(18) For leading references on Pd(II) catalyzed intermolecular en-
antioselective halogenation of olefins, see: (a) El-Qisairi, A.; Hamed, O.;
Henry, P. M. J. Org. Chem. 1998, 63, 2790. (b) Hamed, O.; Henry, P. M.
Organometallics 1998, 17, 5184. (c) El-Qisairi, A.; Henry, P. M. J.
Organomet. Chem. 2000, 603, 50. (d) 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.
Org. Lett., Vol. 13, No. 24, 2011
6351

Table 2. Enantioselective Bromoetherification of γ-Hydroxy-
Scheme 2
alkenesa
Table 3. Enantioselective Bromoaminocyclization of γ-Amino-
alkenesa
a The reactions were carried out with 1 (0.50 mmol), NBS (0.60 mmol),
and 3c (0.05 mmol) in DCM (5.0 mL) at 0 °C for 18 h unless otherwise stated.
b The ratio of isomers was by determined the 1H NMR of the isolated
products. The stereochemistry indicated represents the relative stereochemis-
try. c Isolated yield. d Determined by chiral GC analysis unless otherwise stated.
e Determined by chiral HPLC analysis. f Reacted for 48 h. g Reacted for 72 h.
reaction time. Running the reaction in DCM at 0 °C
appeared to be optimal for both yield and ee.
a The reactions were carried out with 4 (0.30 mmol), NBS (0.36
mmol), and 3c (0.03 mmol) in DCM (3.0 mL) at 0 °C for 72 h unless
otherwise stated. b The ratio of isomers was determined by 1H NMR of
the isolated products. For entries 2 and 8, the absolute configurations
were determined by comparing the optical rotations with L-proline
derivatives after reductive debromination. For entries 1, 3ꢀ7, and
9ꢀ11, the absolute configurations were tentatively proposed by analogy.
For entry 12, the stereochemistry indicated represents the relative
stereochemistry. c Isolated yield. d Determined by chiral HPLC analysis.
e Reacted for 120 h. Ns = 4-Nitrobenzenesulfonyl; Trisyl = 2,4,6-
Triisopropylbenzenesulfonyl.
With the optimized reaction conditions in hand, various
cis-, trans-, and trisubstituted γ-hydroxy-alkenes were
subsequently investigated for the bromocyclization
(Table 2, entries 1ꢀ12). In general, the reaction proceeded
cleanly in all cases examined (63ꢀ96% yield). Only in a few
cases(especiallytrans-olefins), there weresmall amountsof
isomers (possibly 6-endoproducts) formedasjudgedby the
1H NMR (Table 2, entries 7ꢀ10). Up to 81% ee was
obtained for cis- and trans-γ-hydroxy-alkenes (1aꢀk)
(Table 2, entries 1ꢀ11). In the case of the trisubstituted
olefin examined, a much lower enantioselectivity (21% ee)
was obtained (Table 2, entry 12). For phenyl substituted
olefin 1m, the 6-endo product was formed predominately
with little enantioselectivity (Table 2, entry 13).
Further studies showed that various sulfonyl-protected
γ-amino-alkenes were effective substrates. Generally high-
er enantioselectivities (81ꢀ91% ee) were obtained with cis-
γ-amino-alkenes (Table 3, entries 1ꢀ7) as compared to
trans-γ-amino-alkenes (56ꢀ70% ee) (Table 3, entries 8ꢀ11).
6352
Org. Lett., Vol. 13, No. 24, 2011

Good enantioselectivity (74% ee) was also obtained in
the case of the trisubstituted olefin investigated (Table 3,
entry 12). The effect of a sulfonyl protecting group on the
enantioselectivity was found to be highly dependent on
the substrate. For example, in some cases, similar ee’s
were obtained with 4-Ns and Trisyl protected substrates
(Table 3, entry 1 vs 2, entry 3 vs4). However, in other cases,
much lower yields and ee’s were obtained with the 4-Ns
group as compared to the Trisyl group. The stereochemistry
of 5d, 5k, and 5l were determined by the X-ray structures
(Figure 1 and Supporting Information). The absolute con-
figurations of 5b and 5h were determined by comparing the
optical rotations with L-proline derivatives after reductive
debromination (Scheme 2).
While a precise understanding of the origin of the enantios-
electivity awaits further study, a plausible transition state
Figure 3. Proposed transition state model for bromoaminocy-
clization of trans-γ-amino-alkenes.
hydrogen bonding.25 Based on the established configuration
of 5b (Table 3, entry 2), it appears that transition state B is
disfavored for the cis-olefin probably due to the unfavorable
interaction between the triisopropylphenyl group of the
catalyst and the sulfonamide group of the substrate
(Figure 2). For the trans-olefin, transition state C appears
to be favored over D based on the determined configuration
of 5h (Table 3, entry 8) (Figure 3). Generally lower ee’s
obtained for trans-olefins than cis-olefins (Table 3) could be
attributed to the unfavorable interaction between the triiso-
propylphenyl group of the catalyst and the R group of the
substrate in transition state C as compared to A.
Figure 1. X-ray structure of compound 5d.
In summary, we have shown that various γ-hydroxy-
alkenes and γ-amino-alkenes can undergo efficient bromo-
cyclization using NBS as the bromine source and chiral
phosphoric acid as the catalyst, giving 2-substituted tetra-
hydrofurans and tetrahydropyrroles with generally good
yields and up to 91% ee. The current process illustrates the
potential of chiral Brønsted acid catalyzed halogenation21
as a viable approach to enantioselectively functionalize
olefins. Further efforts will be devoted to better under-
standing the origin of enantioselectivity and developing
more effective catalytic systems to improve the enantios-
electivity and to expand the substrate scope as well as
exploring other electrophilic addition reactions.
Acknowledgment. We gratefully acknowledge the Na-
tional Basic Research Program of China (973 program,
2011CB808600), the National Natural Science Founda-
tion of China (21172221), and the Chinese Academy of
Sciences for financial support.
Figure 2. Proposed transition state model for bromoaminocy-
clization of cis-γ-amino-alkenes.
model is proposed in Figures 2 and 3. Phosphoric acid 3c
bearing both acidic and basic sites may act as a bifunc-
tional catalyst to activate both NBS and the nucleophile via
Supporting Information Available. Experimental pro-
cedures, characterization data, X-ray structures (5d, 5k,
and 5l), data for determination of enantiomeric excess,
and NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
(25) When NBS (1.0 equiv) was mixed with acid 3c (1.0 equiv) in
CD2Cl2, no obvious interaction between these two compounds was
1
observed by H NMR. Also little reaction was observed by 1H NMR
when the mixture was kept at 0 °C for 18 h.
Org. Lett., Vol. 13, No. 24, 2011
6353