Samarium metal promoted facile C-acetylation of Baylis-Hillman adducts in the presence of iron(III) chloride and iodine

Article abstract of DOI:10.1055/s-2007-973901

A novel and efficient strategy for the C-acetylation of Baylis-Hillman adducts has been described. Promoted by Sm(0)/Ac₂O/FeCl ₃/I₂, the present method allows for the efficient conversion of Morita-Baylis-Hillman adducts t

Full text of DOI:10.1055/s-2007-973901

LETTER
1115
Samarium Metal Promoted Facile C-Acetylation of Baylis–Hillman Adducts in
the Presence of Iron(III) Chloride and Iodine
C
S
-Acetylation
h
of
B
aylis–H
a
A
dd
o
ucts yu Li, Jian Li, Xueshun Jia*
Department of Chemistry, Shanghai University, Shanghai 200444, P. R. of China
Fax +86(21)66132797; E-mail: xsjia@mail.shu.edu.cn
Received 2 January 2007
we wish to report a novel and efficient strategy for the
stereoselective C-acetylation of MBH adducts promoted
by metallic samarium. To the best of our knowledge, this
Abstract: A novel and efficient strategy for the C-acetylation of
Baylis–Hillman adducts has been described. Promoted by Sm(0)/
Ac O/FeCl /I , the present method allows for the efficient con-
2
3 2
version of Morita–Baylis–Hillman adducts to their corresponding is the first example for the direct C-acylation of MBH
-alkylidene-4-oxoalkanoate derivatives and reduction products. adducts.
2
Key words: Baylis–Hillman adduct, metallic samarium, C-acetyla-
tion, stereoselective
OH
COOMe
O
additives
COOMe
Sm(0), Ac2O
The Morita–Baylis–Hillman (MBH) reaction has become
one of the powerful carbon–carbon bond-forming meth-
ods in organic synthesis. The MBH reaction provides
2a
1a
+
1
COOMe
molecules with hydroxy, alkenyl, and electron-withdraw-
ing groups in close proximity, which makes it valuable for
further chemical transformations. Furthermore, the reac-
2
3a
tion has also been successfully employed in the syntheses3
of biologically active molecules and natural products.
Among these transformations, using their corresponding
acetates as substrates other than the original MBH adducts
is more popular since direct transformation of the hydrox-
yl group is usually difficult. As a result, the direct use of
Baylis–Hillman alcohols in organic synthesis without O-
acetylation continues to be a challenge.
Scheme 1
Our initial experiments were carried out by using MBH
adduct 1a as a model substrate (Scheme 1 and Table 1).
First, we investigated the direct transformation of com-
pound 1a with metallic samarium and acetic anhydride in
the absence of any additives. At room temperature, no re-
action occurred when substrate 1a was mixed with Sm(0)
Due to the synthetic importance of g-ketoesters and 1,4-
diketones, much effort has been put towards the synthesis
of such compounds. As reported previously, using readily
available MBH adducts as substrates provide a new path-
and Ac O in THF. At elevated temperature, the formation
2
of a small amount of O-acetylation product was noted
(
Table 1, entry 1). Addition of 4% of molecular iodine re-
4
sulted in the formation of a small amount of C-acetylation
product (11%) 2a and a reduction product 3a (12%,
Table 1, entry 2).10
way. Recently, Kim described a new synthesis of 2-alky-
lidene-4-oxoalkanoate from Baylis–Hillman acetates.5
However, this synthetic method suffers from the compli-
cated operation which included a S 2¢ conversion fol-
lowed by Nef reaction, thus posing a barrier to their
further applications. Therefore, development of a more
efficient and straightforward method is highly desirable.
N
We also tried adding other amounts of iodine, but most
reactions suffered from low conversion. On the other
hand, excessive iodine resulted in very complex mixtures
6
(
Table 1, entry 3). Notably, addition of FeCl to this sys-
3
tem brought about great improvement. In the presence of
mol% of FeCl , the reaction conversion increased dra-
matically to 100% and the corresponding C-acetylation
The direct use of metallic samarium as a reducing agent in
organic synthesis has attracted much attention in the past
5
3
7
several years. This is due to the fact that metallic samar-
3
+
product 2a and reduction product 3a were afforded in
ium is stable in air and has strong reducing power (Sm /
Sm = –2.41 V). Moreover, it is also cheap and easy to
handle. Recently, we have reported the acylation of alco-
hols with acid chlorides as well as the reduction of MBH
6
1% and 27% yields, respectively (Table 1, entry 5). Sub-
sequent experiments showed that 5 mol% amount of
FeCl appeared to be the best choice (entries 5–7). In spite
3
8
of the important role played by FeCl , the use of iodine is
adducts promoted by metallic samarium. As a continua-
3
9
also indispensable (Table 1, entry 4). A series of experi-
ments were carried out to determine the optimal dosage of
iodine and 4 mol% was found to give the best results
tion of our interest in Baylis–Hillman chemistry, herein
SYNLETT 2007, No. 7, pp 1115–1117
2
4.
0
4.
2
0
0
7
(
Table 1, entry 5). Decreasing amount of iodine led to low
Advanced online publication: 13.04.2007
DOI: 10.1055/s-2007-973901; Art ID: W00107ST
conversion ratios, while the excessive amount resulted in
©
Georg Thieme Verlag Stuttgart · New York

1
116
S. Li et al.
LETTER
Table 1 Optimization on the C-Acetylation of Baylis–Hillman
Adducts 1a Promoted by Metallic Samariuma
Table 2 Stereoselective C-Acetylation of Baylis–Hillman Adducts
a
Promoted by Sm(0)/Ac O System
2
Entry Additive (%)
Time
h)
Conversion Yield (%)b
(%)
Entry
R
Time (h)
Yield (%)b
(
2
a
3a
2
3
1
2
3
4
5
6
7
8
9
0
No additive
I2 (4)
48
24
10
24
10
8
–c
30
–d
50
1
2
3
4
5
Ph
10
22
24
8
61
63
65
60
69
27
28
23
31
18
11
12
4-MeC H
6
4
I2 (50)
4-MeOC H
6
4
4
FeCl (5)
20
61
57
50
27
54
41
26
27
33
42
24
35
50
3-MeOC H
3
6
I (4), FeCl (5)
100
100
100
54
4-t-BuC H
4
14
2
3
6
I (4), FeCl (10)
O
2
3
6
10
56
30
I (4), FeCl (15)
8
2
3
O
I (1), FeCl (5)
24
10
10
7
8
9
2-ClC H
6
12
18
50
40
57
47
49
33
2
3
6
4
4
I (3), FeCl (5)
100
100
4-ClC H
2
3
6
1
I (5), FeCl (5)
4-BrC H
2
3
6
4
a
All reactions were carried out with samarium powder (6 equiv) and
1
0
40
30
28
Ac O in THF (15 mL) under reflux.
2
b
Isolated yields.
Only a small amount of O-acetylation product was obtained.
O
c
a
d
Unless otherwise noted, all reactions proceeded with MBH adduct 1
1 mmol), Sm powder (6 mmol) and Ac O (6 mmol) in the presence
A very complex mixture was formed.
(
2
of FeCl (5 mol%) and I (4 mol%) in THF (15 mL) under reflux.
3
2
b
Isolated yields.
poorer selectivity (Table 1, entry 8–10). In addition, the
present transformation was highly E-stereoselective and
1
1
no Z-isomer was observed.
conversion produced.12 Furthermore, the presence of
With the Sm(0)/Ac O/FeCl /I system optimized, we then FeCl was also considered to facilitate the elimination of
2
3
2
3
13
turned our attention to other reaction substrates the hydroxyl group in MBH adducts. Further studies on
Scheme 2). Various MBH adducts were examined under reaction mechanism are still under way in our laboratory.
(
the optimal conditions and the results were summarized in
Table 2. First, a series of electron-rich MBH adducts were
applied to the above conversion and excellent selectivities
were observed in all cases (Table 2, entry 2–5). As can be
seen, the C-acetylation products were obtained as major
products (60–69% yield) even though long reaction time
was needed. On the other hand, the presence of electron-
withdrawing group shortened the reaction time but the
In summary, we have provided a facile and novel method-
ology for the synthesis of g-ketoesters from MBH
14
adducts. This new protocol allows for the direct C-ace-
tylation of MBH adducts. We believe that this procedure
will be an excellent alternative to existing literature
methods.
yields of desired products 2 decreased to some extent and Acknowledgment
more reduction products 3 were isolated. Notably, the
We thank the National Natural Science Foundation of China (No:
present methodology showed excellent E-stereoselectivi-
ty and no Z-isomer was detected.
2
0472048 and 20572068) for financial support.
As to the mechanism, an acyl anion intermediate formed
References and Notes
in situ by Sm and Ac O mixture may be involved in this
2
(
1) For reviews, see: (a) Ciganek, E. Org. React. 1997, 51, 201.
b) Basavaiah, D.; Rao, P. D.; Hyma, R. S. Tetrahedron
996, 52, 8001. (c) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811.
(
1
COOMe
OH
R
Sm(0), Ac2O, FeCl3, I2
COOMe
(2) For selected examples: (a) Ramachandran, P. V.; Madhi, S.;
Bland-Berry, L.; Reddy, M. V. R.; O’Donnel, M. J. J. Am.
Chem. Soc. 2005, 127, 13450. (b) Kabalka, G. W.;
O
R
THF, reflux
2
+
1
Venkataiah, B.; Dong, G. Organometallics 2005, 24, 762.
COOMe
(c) Chung, Y. M.; Gong, J. H.; Kim, T. H.; Kim, J. N.
R
Tetrahedron Lett. 2001, 42, 9023. (d) Singh, V.; Saxena, R.;
Batra, S. J. Org. Chem. 2005, 70, 353. (e) Patra, A.; Roy, A.
K.; Batra, S.; Bhaduri, A. P. Synlett 2003, 1819.
3
Scheme 2
Synlett 2007, No. 7, 1115–1117 © Thieme Stuttgart · New York

LETTER
C-Acetylation of Baylis–Hillman Adducts
1117
(
3) For recent examples: (a) Radha Krishna, P.; Nasingam, M.;
(12) (a) Collin, J.; Namy, J. L.; Dallemer, F.; Kagan, H. B. J. Org.
Chem. 1991, 56, 3118. (b) Liu, Y. J.; Wang, X. X.; Zhang,
Y. M. Synth. Commun. 2004, 34, 4009.
Kannan, V. Tetrahedron Lett. 2004, 45, 4773. (b) Rodgen,
S. A.; Schaus, S. E. Angew. Chem. Int. Ed. 2006, 45, 3913.
(
4
c) Drewes, S. E.; Roos, G. H. P. Tetrahedron 1988, 44,
653. (d) Brzezinski, L. J.; Rafel, S.; Leahy, J. M. J. Am.
(13) Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M.
Angew. Chem. Int. Ed. 2005, 44, 3913.
Chem. Soc. 1997, 119, 4317. (e) Wori, M.; Kuroda, S.;
Dekura, F. J. Am. Chem. Soc. 1999, 121, 5591. (f) Trost, B.
M.; Thiel, O. R.; Tsui, H. C. J. Am. Chem. Soc. 2003, 125,
(14) General Procedure for C-Acetylation of Baylis–Hillman
Adducts
To a stirred solution of 6 mmol Sm powder (0.9 g) and
6 mmol Ac O (0.6 g) in 15 mL THF, 5 mol% FeCl , 4 mol%
13155.
2
3
(
(
(
4) Chamakh, A.; Mhirsi, M.; Villieras, J.; Lebreton, J.; Amri,
H. Synthesis 2000, 295.
5) Kim, J. M.; Im, Y. J.; Kim, T. H.; Kim, J. N. Bull. Korean
Chem. Soc. 2002, 23, 657.
6) Conditions for Nef reaction, see: (a) Das, N. B.; Sarma, J.
C.; Sharma, R. P.; Bordoloi, M. Tetrahedron Lett. 1993, 34,
I2 and 1 mmol Baylis–Hillman adduct 1 were added. The
resulting mixture was then allowed to reflux in the air. Until
completion of the reaction, 3 mL HCl (1 M) was then added
to quench the reaction and the mixture was successively
exacted with CH Cl (3 × 20 mL). The organic phase was
2
2
washed with 15 mL sat. brine, dried over anhyd Na SO , and
2
4
8
69. (b) Shechter, H.; Williams, F. T. J. Org. Chem. 1962,
filtered. The solvent was removed under reduced pressure to
give the crude products, which were purified by column
chromatography using EtOAc and PE (1:10) as eluent.
27, 3699. (c) Aizpurua, J. M.; Polomo, O. C. Tetrahedron
Lett. 1987, 28, 5361.
(
(
7) For review, see: Banik, B. K. Eur. J. Org. Chem. 2002, 2431.
8) (a) Jia, X.; Wang, H.; Huang, Q.; Kong, L.; Zhang, W. J.
Chem. Res. 2006, 135. (b) Li, J.; Xu, H.; Zhang, Y. M.
Tetrahedron Lett. 2005, 46, 1931.
Selected spectroscopic data for compounds 2 follow.
1
Compound 2a (R = Ph): H NMR (500 MHz, CDCl ): d =
3
7.93 (s, 1 H), 7.37–7.27 (m, 5 H), 3.80 (s, 3 H), 3.62 (s, 2 H),
1
3
2.25 (s, 3 H). C NMR (500 MHz, CDCl ): d = 206.1, 167.8,
3
(
9) (a) Li, J.; Wang, X. X.; Zhang, Y. M. Tetrahedron Lett.
142.2, 135.0, 128.9, 128.7, 128.6, 126.6, 52.2, 42.5, 30.1. IR
(film): 3058, 2952, 2847, 1703, 1639, 1575, 1492, 1437,
2
2
005, 46, 5233. (b) Li, J.; Wang, X. X.; Zhang, Y. M. Synlett
005, 1039. (c) Li, J.; Qian, W. X.; Zhang, Y. M.
–
1
1359, 1264, 1098, 764, 700 cm .
1
Tetrahedron 2004, 60, 5793.
Compound 2b (R = 3-MeOC H ): H NMR (500 MHz,
6 4
1
(
(
10) All new compounds were characterized by H NMR, 13C
CDCl ): d = 7.90 (s, 1 H), 7.30–6.84 (m, 4 H), 3.81 (s, 3 H),
3
1
3
NMR, IR spectroscopy, and elemental analysis.
3.80 (s, 3 H), 3.63 (s, 2 H), 2.26 (s, 3 H). C NMR (500
11) The stereochemistry of product 2 was all E, as was that of
MHz, CDCl ): d = 206.6, 168.4, 160.1, 142.8, 136.9, 130.2,
3
product 3.9 The H NMR spectrum of 2 was in good
c
1
127.4, 121.6, 115.2, 114.5, 55.8, 52.8, 43.2, 30.7. IR (film):
3001, 2953, 2850, 1706, 1637, 1600, 1580, 1488, 1433,
5
agreement with the reported data.
–
1
1
359, 1247, 1098, 790, 690 cm .
Synlett 2007, No. 7, 1115–1117 © Thieme Stuttgart · New York

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