Amination of the Baylis-Hillman acetates in ethanol

Article abstract of DOI:10.1080/00397910701465370

Baylis-Hillman acetates in EtOH were substituted by various nitrogen nucleophiles to give the corresponding trisubstituted alkenes in high yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701465370

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Amination of the Baylis–Hillman Acetates in
Ethanol
Young Sang Park a , Min Young Cho b , Young Bum Kwon b , Byung Woo Yoo b
Cheol Min Yoon b
&
a Graduate School of Biotechnology, Korea University, South Korea
b Department of New Material Chemistry, Korea University, South Korea
Published online: 14 Aug 2007.
To cite this article: Young Sang Park , Min Young Cho , Young Bum Kwon , Byung Woo Yoo & Cheol
Min Yoon (2007) Amination of the Baylis–Hillman Acetates in Ethanol, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:16, 2677-2685, DOI:
10.1080/00397910701465370
To link to this article: http://dx.doi.org/10.1080/00397910701465370
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Synthetic Communicationsw, 37: 2677–2685, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701465370
Amination of the Baylis–Hillman Acetates
in Ethanol
Young Sang Park
Graduate School of Biotechnology, Korea University, South Korea
Min Young Cho, Young Bum Kwon, Byung Woo Yoo, and
Cheol Min Yoon
Department of New Material Chemistry, Korea University, South Korea
Abstract: Baylis–Hillman acetates in EtOH were substituted by various nitrogen
nucleophiles to give the corresponding trisubstituted alkenes in high yields.
Keywords: Baylis–Hillman acetates, amination, trisubstituted alkene
The Baylis–Hillman reaction is one of the carbon–carbon bond-forming
reactions in organic synthesis.[1] The Baylis–Hillman adducts were prepared
by the reaction of activated alkenes such as ethyl acrylate, acrylonitrile, and
methyl vinyl ketone with aldehydes or imines in the presence of nucleophilic
catalysts such as 1,4-diazabicyclo[2.2.2]octane (DABCO), quinuclidine, 4-
(N,N-dimethylamino)pyridine (DMAP), and phosphine.[2] In addition to the
usefulness of the Baylis–Hillman adducts by themselves, they and their
acetates are very useful precursors for the preparation of a variety of trisubsti-
tuted alkenes with various functional groups such as ester, ketone, and nitriles
by the reaction with a variety of nucleophiles.[3,4] Quinoline and dihydroquino-
lines are the important moiety of biological active compounds in medicinal
chemistry[5–7] and prepared from the Baylis–Hillman adducts.[3b,4]
During a study for the palladium-catalyzed one-pot synthesis of dihydro-
quinolines 3 by the reaction of the Baylis–Hillman adducts or their acetates 1
Received July 21, 2006
Address correspondence to Cheol Min Yoon, Department of Advanced Material
Chemistry, Korea University, Jochiwon, Chungnam Korea. E-mail: cmyoon@korea.
ac.kr
2677

2678
Y. S. Park et al.
Scheme 1.
with p-toluidine (Scheme 1), Baylis–Hillman acetates 1 were found to
undergo the substitution to give the corresponding substituted amines 4.
Amination of the Baylis–Hillman acetates was one of the most
straightforward reactions to synthesize the corresponding trisubstituted
alkenes with amino functional group. However, only two methods have
been reported, to the best of our knowledge: the substitution of the Baylis–
Hillman acetates with amine nucleophile in THF under reflux[8] and the
palladium-catalyzed substitution of the Baylis–Hillman acetate in THF
using Pd (PPh3)4 at rt.[9] The two reactions posed some problems such as rela-
tively low yield, extended reaction time, high reaction temperature, low
regioselectivity, and generality. Here we are going to report a mild,
efficient, and convenient protocol for the nucleophilic displacement of the
Baylis–Hillman acetates by aromatic amine, benzylamine, and potassium
phthalimide in EtOH at rt to give the corresponding trisubsituted alkenes 3
in good to high yields (Scheme 2).
The optimum condition was investigated using ethyl 2-(acetoxy(2-
bromo-phenyl)methyl)acrylate as a model substrate and p-toluidine as an
amine nucleophile in various solvent systems such as acetonitrile, THF,
DMSO, ethanol, and water in the presence or absence of palladium catalyst.
Various palladium reagents did not have any role in the reaction, and EtOH
turned out to be the choice of solvent. The reaction of ethyl 2-(acetoxy(2-
bromophenyl)methyl)- acrylate in ethanol after 8 h gave the trisubstituted
product in 87% isolated yield as shown in entry 1 of Table 1. With this
result in hand, the substitution of ethyl 2-(acetoxyarylmethyl)acrylates with
p-anizidine, benzylamine, potassium phthalimide, p-toluenesulfonylamide,
diethylamine, and N-benzylmethylamine under optimized condition were
attempted to give the corresponding products with (E)-stereoselectivity
(entries 2–13). The reaction of ethyl 2-(acetoxyphenylmethyl)acrylate with
amides such as acetamide and t-butoxycarbamate did not proceed at
Scheme 2.

Table 1. Amination of the Baylis–Hillman acetates in EtOH
Entry
1
Acetate
Nucleophile
p-Toluidine
Product
Time (h)
8
Yield (%)a
87.0
2
p-Anisidine
8
82.0
3
4
Benzylamine
8
8
90.0
83.6
Potassium phthalimide
(continued)

Table 1. Continued
Entry
Acetate
Nucleophile
Product
Time (h)
8
Yield (%)a
71.2
5
6
p-Toluenesulfonylamide
p-Toluidine
p-Anisidine
8
8
94.6
92.0
7
8
9
Benzylamine
4
4
87.3
80.1
Potassium phthalimide

10
11
Diethylamine
2
2
84.5
92.3
N-Bezylmethylamine
12
p-Anisidine
5
90.5
13
14
Potassium phthalimide
6
4
86.0
92.0
p-Toluidine
(continued)

Table 1. Continued
Entry
Acetate
Nucleophile
p-Anisidine
Product
Time (h)
3
Yield (%)a
94.0
15
16
17
Benzylamine
6
5
82.0
82.3
Potassium phthalimide
18
19
p-Anisidine
1
3
94.8
87.2
Potassium phthalimide

20
21
p-Anisidine
8
3
97.0
91.4
Potassium phthalimide
22
23
p-Toluidine
p-Anizidine
8
1
97.0
89.3
24
25
Benzylamine
2
4
85.0
81.0
Potassium phthalimide
aIsolated yields.

2684
Y. S. Park et al.
all, even under reflux condition. b-Acetoxy-a-methylene ketones reacted with
p-toluidine, p-anizidine, benzylamine, and potassium phthalimide in ethanol
at rt to afford the corresponding products (E)-stereoselectively in good to
high isolated yields (entries 14–19). Further, the reactions of 3-acetoxy-2-
methylene-3-phenylacrylonitriles with p-toluidine, p-anizidine, benzylamine,
and potassium phthalimide in ethanol produced the corresponding alkenes
having (Z)-stereochemistry in good to high yields (entries 20–25).
The amination product prepared from Baylis–Hillman adduct was
attempted for the cyclization.[10] A amine obtained by the reaction of
Baylis–Hillman acetate and p-toluenesulfonylamide in ethanol at rt
undergoes the cyclization in the presence of palladium acetate and BINAP
in toluene at 1008C for 12 h to give a dihydroquinoline in 82% yield
(Scheme 3). The dihydroquinoline generated during the reaction seemed to
be quite stable under the reaction condition even after a long reaction time
(48 h), based on thin-layer chromatography (TLC). The further study for the
one-pot synthesis of dihydroquinolines from Baylis–Hillman acetate using
palladium catalyst are under way.[11]
In summary, we have described a simple, convenient, and efficient
protocol for the substitution reaction by various amines and amides on
Baylis–Hillman acetates in EtOH at rt to give the corresponding trisubstituted
alkenes in good to high yields. A success of palladium-catalyzed cyclization
of a Baylis–Hillman amine opened the possibility of new synthetic route
for the dihydroquinoline.
EXPERIMENTAL
General Procedure
The mixture of Baylis–Hillman acetate (0.1528 mmol) and amine (0.3056 mmol,
2 equiv) in EtOH (1 mL) was stirred at room temperature for the appropriate
time (see Table 1). After the reaction was complete (monitored by TLC using
a solution of EA and hexane), the reaction mixture was concentrated under
reduced pressure, and the concentrate was chromatographed on a short
silica-gel pad using a solution of ethyl acetate and hexane (1:10) to give the
corresponding products in good to high yield.
Scheme 3.

Amination of the Baylis–Hillman Acetates in Ethanol
ACKNOWLEDGMENT
2685
The authors acknowledge the financial support of the Korea Science and
Engineering Foundation in the proceeding program in 2005.
REFERENCES
1. (a) Baylis, A. B.; Hillman, M. E. D. German Patent 1972, 2155113; (b)
Baylis, A. B.; Hillman, M. E. D. Chem. Abstr. 1972, 77, 34174q;
(c) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44, 4653.
2. Basabaiah, D.; Jaganmohan Rao, A.; Satyanarayana, T. Chem. Rev. 2003, 103,
811.
3. (a) Kim, J. N.; Im, Y. J.; Gong, J. H.; Lee, K. Y. Tetrahedron Lett. 2001, 42, 4195;
(b) Kim, J. N.; Lee, K. Y.; Kim, H. S.; Kim, T. Y. Org. Lett. 2000, 2, 343;
(c) Kim, H. S.; Kim, T. Y.; Lee, K. Y.; Chung, Y. M.; Lee, H. J.; Kim, J. N. Tetra-
hedron Lett. 2000, 41, 2613; (d) Lee, H. J.; Kim, H. S.; Kim, J. N. Tetrahedron
Lett. 1999, 40, 4363; (e) Lee, H. J.; Seong, M. R.; Kim, J. N. Tetrahedron Lett.
1998, 39, 6223; (f) Basavaiah, D.; Kumaragurubaran, N.; Sharada, D. S. Tetra-
hedron Lett. 2001, 42, 85; (g) Basavaiah, D.; Kumaragurubaran, N. Tetrahedron
Lett. 2001, 42, 477; (h) Yang, K.-S.; Chen, K. Org. Lett. 2000, 2, 729;
(i) Chamakh, A.; Amri, H. Tetrahedron Lett. 1998, 39, 375; (j) Madapa, S.;
Singh, V.; Batra, S. Tetrahedron Lett. 2006, 62, 8740.
4. (a) Familoni, O. B.; Kaye, P. T.; Klaas, P. J. J. Chem. Soc., Chem. Commun. 1998,
2563; (b) Bode, M. L.; Kaye, P. T. J. Chem. Soc., Perkin Trans. 1 1993, 1809;
(c) Bode, M. L.; Kaye, P. T. J. Chem. Soc., Perkin Trans. 1 1990, 2612;
(d) Amri, H.; El Gaied, M. M.; Ben Ayed, T.; Villieras, J. Tetrahedron Lett.
1992, 33, 6159; (e) Amri, H.; El Gaied, M. M.; BenAyed, T.; Villieras, J. Tetra-
hedron Lett. 1992, 33, 7345; (f) Jungheim, L. N. Tetrahedron Lett. 1989, 30, 1889.
5. (a) Michael, J. P. Nat. Prod. Rep. 1997, 14, 605; (b) Balasubramanian, M.;
Keay, J. G. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.,
Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: Oxford, 1996; Vol. 5, p. 245.
6. Jones, G. Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees and
C. W., Scriven, E. F. V. Eds.; Pergamon: Oxford, 1996; Vol. 5, p. 167.
7. (a) Ranu, B. C.; Hajra, A.; Jana, U. Tetrahedron Lett. 2000, 41, 531; (b) Cho, C. S.;
Oh, B. H.; Shim, S. C. Tetrahedron Lett. 1999, 40, 1499; (c) Cacchi, S.; Fabrizi, G.;
Marinelli, F. Synlett. 1999, 401; (d) Suginome, M.; Fukuda, T.; Ito, Y. Org. Lett.
1999, 1, 1977; (e) Katritzky, A. R.; Arend, M. J. Org. Chem. 1998, 63, 9989;
(f) Ruhland, T.; Kunzer, H. Tetrahedron Lett. 1996, 37, 2757; (g) Radl, S.;
Bouzard, D. Heterocycles 1992, 34, 2143; (h) Qiang, L. G.; Baine, N. H. J. Org.
Chem. 1988, 53, 4218.
8. Lee, C. G.; Lee, K. Y.; Gowrisankar, S.; Kim, J. N. Tetrahedron Lett. 2004, 45,
7409.
9. Rajesh, S.; Banerji, B.; Iqbal, J. J. Org. Chem. 2002, 67, 7852.
10. (a) Kim, J. N.; Lee, H. J.; Lee, K. Y.; Kim, H. S. Tetrahedron Lett. 2001, 42, 3737;
(b) Kim, J. N.; Kim, H. S.; Gong, J. H.; Chung, Y. M. Tetrahedron Lett. 2001, 42,
8341.
11. (a) Hamann, B. C.; Hartwig, J. F. J. Am. Chem. Soc. 1998, 120, 7369;
(b) Lebedev, A. Y.; Khartulyari, A. S.; Voskoboynikov, A. Z. J. Org. Chem.
2005, 70, 596–602.