Generation of diverse 2 H-isoindol-1-ylphosphonates via three-component reaction of 2-alkynylbenzaldehyde, aniline, and phosphite

Article abstract of DOI:10.1021/cc100101a

Diverse 2H-isoindol-1-ylphosphonates as potential HCT-116 inhibitors are easily generated via a FeCl₃ and PdCl₂ cocatalyzed three-component reaction of 2-alkynylbenzaldehyde, aniline, and phosphite. The focused small library is constructed based on parallel diversity-oriented synthesis.

Full text of DOI:10.1021/cc100101a

J. Comb. Chem. 2010, 12, 743–746
743
Generation of Diverse 2H-Isoindol-1-ylphosphonates via
Three-Component Reaction of 2-Alkynylbenzaldehyde, Aniline, and
Phosphite
Xingxin Yu,† Qiuping Ding,‡ and Jie Wu*,†
Department of Chemistry, Fudan UniVersity, 220 Handan Road, Shanghai 200433, China, and College
of Chemistry and Chemical Engineering, Jiangxi Normal UniVersity, Nanchang 330027, China
ReceiVed June 13, 2010
Diverse 2H-isoindol-1-ylphosphonates as potential HCT-116 inhibitors are easily generated via a FeCl3 and
PdCl2 cocatalyzed three-component reaction of 2-alkynylbenzaldehyde, aniline, and phosphite. The focused
small library is constructed based on parallel diversity-oriented synthesis.
Introduction
Parallel diversity-oriented synthesis of discrete molecules
has become a useful technology for the rapid preparation of
focused libraries.1 Among N-heterocycles, less attention has
been paid to isoindoles.2 Various isoindoles have become
known for both their plant growth regulating3a and fluores-
cent properties.2b Recently, we described an efficient syn-
thesis of 2,3-disubstituted-2H-isoindol-1-ylphosphonates
via palladium(II)-catalyzed reaction of R-amino (2-alkynyl-
phenyl)methylphosphonate.2e,f The 5-exo-cyclization and
[1,5]-H shift were involved in this transformation. Subse-
quent biological assays revealed that several compounds of
phosphonylated isoindoles displayed promising activity as
HCT-116 (human colon cancer cells) inhibitors. Compound
A shows the best activity with an IC50 9.90 µM (Figure 1).
In addition, mechanistic studies show that this compound
causes destabilization of microtubules, leading to a cell cycle
arrest at G2/M stage.3b The discovery of promising lead
antitumor compounds with moderate activity prompted us
to develop efficient and rapid synthesis protocol and test the
resulting compounds to find better inhibitors. Consequently,
we initiated a program to develop efficient methods for facile
assembly of diverse 2H-isoindol-1-ylphosphonate molecules
(Figure 1).
Figure 1. 2H-Isoindol-1-ylphosphonates.
R-amino (2-alkynylphenyl)methylphosphonate.2e The starting
material, R-amino (2-alkynylphenyl)methylphosphonate, was
traced back to the 2-alkynylbenzaldehyde, amine, and
phosphite. However, the initial examination revealed that
three-component reaction of 2-alkynylbenzaldehyde, amine,
and phosphite, in the presence of palladium or copper
catalyst, produced 1,2-dihydroisoquinolin-1-ylphosphonates
via 6-endo cyclization.6a While selectivity and efficiency are
the major concerns in this transformation, based on the
different reactivity of Lewis acids7 and the advancement of
multicatalysis and tandem reactions,8 we conceived that the
phosphonylated isoindoles might be generated in a selective
way using a suitable cocatalytic system. Thus, we started to
explore the possibility to form the phosphorylated isoindoles
via the three-component reaction of 2-alkynylbenzaldehyde,
amine, and phosphite.
Recently, multicatalytic processes have attracted consider-
able interest.4,5 Normally, several catalysts are combined in
a reaction and promote two or more distinct chemical
transformations in one pot. For instance, Lambert and co-
workers described the multicatalytic synthesis of R-pyrro-
lidinyl ketones in the presence of palladium(II) and indium-
(III) catalysts.5i Silver triflate and bismuth triflate proved to
be effective as cocatalysts for the tandem reaction of
2-alkynylbenzaldoxime with isocyanide.5m As mentioned
above, the 2,3-disubstituted-2H-isoindol-1-ylphosphonates
were generated from palladium(II)-catalyzed reaction of
Result and Discussion
2-Alkynylbenzaldehydes 1 were synthesized via Sono-
gashira coupling reaction according to the literature report.9
The initial idea was to react 2-alkynylbenzaldehyde 1{1},
p-toluidine 2{3}, and diethyl phosphite in the presence of
different Lewis acids in using different solvents at 60 °C
(Scheme 1). Starting with acetonitrile in the presence of 5
mol % of Lewis acids (FeCl3, Bi(OTf)3, Yb(OTf)3, Dy(OTf)3,
Zn(OTf)2, AgOTf, Sc(OTf)3, In(OTf)3, Mg(ClO4)2) did not
lead to the desired product 3{1,3}. Only R-amino (2-
alkynylphenyl)methylphosphonate or compound 4{1,3} was
generated (Scheme 1). Among the reactions, compound
4{1,3} was isolated when AgOTf or PdCl2 was used as the
catalyst,6 while R-amino (2-alkynylphenyl)methylphospho-
* To whom correspondence should be addressed. E-mail: jie_wu@
fudan.edu.cn.
† Fudan University.
‡ Jiangxi Normal University.
10.1021/cc100101a  2010 American Chemical Society
Published on Web 08/18/2010

744 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5
Yu et al.
Scheme 1. Initial Studies for the Reaction of 2-Alkynylbenzaldehyde 1{1}, Aniline 2{3}, and Diethyl Phosphite
nate was obtained when other metal salts were utilized
(Kabachnik-Fields reaction).10 The Kabachnik-Fields reac-
tion (three-component reaction of aldehyde, amine, and
phosphite) is well studied, and many Lewis acids have been
successfully employed in such reaction. Since FeCl3 was the
most effective catalyst for R-amino (2-alkynylphenyl)meth-
ylphosphonate formation10j and the palladium catalyst worked
efficiently for the subsequent 5-exo-cyclization,2e the above
reactions were performed again in combination with 5 mol
% of PdCl2. To avoid the competitive pathway, this three-
component reaction was performed in the presence of Lewis
acid (5 mol %) for 30 min to facilitate the R-amino
(2-alkynylphenyl)methylphosphonate formation. Next, 5 mol
% of PdCl2 was added in the mixture for the subsequent
transformation. The desired product 3{1,3} was isolated in
59% yield when the reaction was carried out in the presence
of FeCl3 (5 mol %) and PdCl2 (5 mol %) in MeCN at 60
°C. Other combinations of PdCl2 with Lewis acids gave
inferior results. With these promising results, we started to
screen solvents for the reaction. We found that the reaction
worked most efficiently in DCE/MeCN (V/V 1:1) with 77%
isolated yield. Reactions performed in other solvents led to
inferior results with low yields and prolonged reaction time.
No effects were observed for the concentration screening.
The reaction was retarded when the temperature was
decreased to 25 °C. Further, a reduction of the amount to 1
mol % diminished the progress of the reaction.
1 and amines 2. The diverse reagents are shown in Figures
2 and 3. This cocatalytic system proved to be highly efficient
and we found a good general applicability of the protocol
because of its remarkable functional group compatibility,
which afforded the desired phosphonylated isoindoles 3 in
good to excellent yields (Table 1). Moreover, the conditions
proved to be useful for various anilines. As expected, both
electron-rich and electron-poor anilines were suitable partners
in this process. Different functional groups such as methyl,
methoxy, hydroxy, acetyl, ester, cyano, nitro, halo, and
trifluoromethyl groups were all tolerated under standard
conditions. With respect to 2-alkynylbenzaldehyde 1, it
seemed that the R2 group attached to the triple bond was
crucial for the transformation. No desired product formation
was observed when substrate 1{6} was employed in the
reaction with aniline 2{1} and diethyl phosphite. We
reasoned that the presence of aryl group (R2) attached to the
triple bond might facilitate its [1,5]-H shift after 5-exo-
cyclization in the reaction process. When dimethoxy-
substituted 2-alkynylbenzaldehyde 1{5} was utilized in the
reactions with aniline 2{1} or 2{3} with diethyl phosphite,
the desired products were observed in low yields. The
electron-donating groups attached to the aromatic ring of
2-alkynylbenzaldehyde proved to decrease the electrophilicity
of the substrate. When nitro-substituted 2-alkynylbenzalde-
hyde 1{7} was employed in the three-component reaction,
the corresponding products were isolated in moderate yield
(entries 52-55). This result indicated that the presence of
strong electron-withdrawing nitro group in the aromatic ring
might reduce the nucleophilicity of amine in the intermediate
R-amino (2-alkynylphenyl)methylphosphonate.
Using optimized conditions (5 mol % of FeCl3, 5 mol %
of PdCl2, DCE/CH3CN, 60 °C), we investigated the scope
of this cocatalytic system with regard to tolerance of
functional groups in case of different 2-alkynylbenzaldehydes
Conclusion
In conclusion, we have described a facile and efficient
route for the generation of diverse 2H-isoindol-1-ylphos-
phonates via a FeCl3 and PdCl2 cocatalyzed three-component
reaction of 2-alkynylbenzaldehydes, anilines, and phosphite.
The focused library was prepared based on parallel diversity-
oriented synthesis. However, some limitations were observed
for the substrate selection: Electron-donating groups attached
Figure 2. Diversity reagents 1{1-7}.
Figure 3. Aniline reagents 2{1-15}.

Diverse 2H-Isoindol-1-ylphosphonates
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5 745
Table 1. Generation of Diverse 2H-Isoindol-1-ylphosphonates
via Three-Component Reaction of 2-Alkynylbenzaldehyde 1,
Aniline 2, and Phosphite
116 inhibitors. Further investigations are ongoing and the
results will be published in due time.
Experimental Section
General Experimental Procedure for FeCl3 and PdCl2
Co-catalyzed Three-Component Reaction of 2-Alkynyl-
benzaldehyde 1, Aniline 2, and Phosphite. Iron(III) chlo-
ride (0.015 mmol, 5 mol %) was added to a solution of
2-alkynylbenzaldehyde1 (0.3 mmol), aniline 2 (0.3 mmol,
1.0 equiv), and diethyl phosphite (0.36 mmol, 1.2 equiv) in
DCE (1.0 mL). The mixture was heated at 60 °C with
vigorous stirring for 30 min. Next, palladium(II) chloride
(0.015 mmol, 5 mol %) and MeCN (1.0 mL) were added to
the solution. The reaction mixture was then vigorously stirred
at 60 °C until completion of the reaction. After the solution
was cooled to room temperature, the mixture was diluted
with ethyl acetate (5.0 mL) and quenched with water (5.0
mL). The organic layer was washed with brine, dried over
anhydrous Na2SO4, and concentrated under reduced pressure.
The crude residue was purified by column chromatography
on silica gel (eluting with PE/EA ) 3/1 to 1/1) to provide
the desired product 3.
Selected Examples. Diethyl 3-Benzyl-2-phenyl-2H-
isoindol-1-ylphosphonate 3{1,1}. 1H NMR (400 MHz,
CDCl3): 1.12 (t, J ) 7.2 Hz, 6H), 3.79-3.85 (m, 2H),
3.90-3.96 (m, 2H), 4.13 (s, 2 H), 6.82 (t, J ) 3.6 Hz, 2H),
7.07 (t, J ) 7.2 Hz, 1H), 7.12-7.23 (m, 6H), 7.37 (t, J )
7.6 Hz, 2H), 7.44 (d, J ) 7.2 Hz, 1H), 7.57 (t, J ) 8.0 Hz,
1H), 8.15 (d, J ) 8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3):
δ 16.1, 31.1, 61.6, 107.7 (d, 1J CP ) 234 Hz), 119.6, 120.6,
121.7, 123.3 (d, 3J CP ) 13 Hz), 124.8, 126.2, 128.2, 128.3,
128.4, 128.5, 129.1, 131.5 (d, 3J CP ) 9 Hz), 132.8 (d, 2J CP
) 19 Hz), 138.1, 138.5. 31P NMR (161 MHz, CDCl3): δ
10.1. HRMS calcd for C25H26NO3P: (M + H+) 420.1729,
found 420.1720.
entry
aldehyde 1
amine 2
product
yield (%)a
purityd
1
2
3
4
5
6
7
8
1{1}
1{1}
1{1}
1{1}
1{1}
1{1}
1{1}
1{1}
1{1}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{2}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{3}
1{4}
1{4}
1{4}
1{4}
1{4}
1{4}
1{4}
1{4}
1{4}
1{4}
1{4}
1{5}
1{5}
1{6}
1{7}
1{7}
1{7}
1{7}
2{1}
2{2}
2{3}
2{5}
3{1,1}
3{1,2}
3{1,3}
3{1,5}
3{1,6}
3{1,11}
3{1,12}
3{1,14}
3{1,15}
3{2,1}
3{2,2}
3{2,3}
3{2,4}
3{2,5}
3{2,6}
3{2,7}
3{2,8}
3{2,9}
3{2,10}
3{2,11}
3{2,12}
3{2,13}
3{2,14}
3{2,15}
3{3,1}
3{3,2}
3{3,3}
3{3,5}
3{3,6}
3{3,7}
3{3,9}
3{3,10}
3{3,11}
3{3,12}
3{3,13}
3{3,14}
3{3,15}
3{4,1}
3{4,3}
3{4,5}
3{4,6}
3{4,9}
3{4,10}
3{4,11}
3{4,12}
3{4,13}
3{4,14}
3{4,15}
3{5,1}
3{5,3}
3{6,1}
3{7,1}
3{7,3}
3{7,6}
3{7,11}
76
60
77
66
80
70
70
70
71
85
70
80
63
74
66
61
66
73
76
80
72
61
88
74
76
73
81
82
78
90
91
94
76
81
84
84
86
96
91
80
94
60
96
80
70
77
90
96
<20b
<20b
c
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
>97%
2{6}
2{11}
2{12}
2{14}
2{15}
2{1}
2{2}
2{3}
2{4}
2{5}
2{6}
2{7}
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
2{8}
2{9}
2{10}
2{11}
2{12}
2{13}
2{14}
2{15}
2{1}
2{2}
2{3}
2{5}
2{6}
2{7}
2{9}
2{10}
2{11}
2{12}
2{13}
2{14}
2{15}
2{1}
2{3}
2{5}
2{6}
2{9}
2{10}
2{11}
2{12}
2{13}
2{14}
2{15}
2{1}
2{3}
2{1}
2{1}
2{3}
Diethyl 3-Benzyl-2-o-tolyl-2H-isoindol-1-ylphosphonate
1
3{1,2}. H NMR (400 MHz, CDCl3): 1.10 (t, J ) 7.3 Hz,
3H), 1.15 (t, J ) 7.3 Hz, 3H), 1.66 (s, 3H), 3.81-3.96 (m,
4H), 3.95 (d, J ) 16.0 Hz, 1H), 4.09 (d, J ) 15.6 Hz, 1H),
6.80-6.82 (m, 2H), 7.01 (d, J ) 7.8 Hz, 1H), 7.05-7.12
(m, 4H), 7.17-7.23 (m, 3H), 7.37 (t, J ) 7.8 Hz, 1H), 7.61
(d, J ) 8.2 Hz, 1H), 8.13 (d, J ) 8.7 Hz, 1H). 13C NMR
(100 MHz, CDCl3): δ 16.1, 17.0, 31.3, 61.7, 107.1 (d, 1J CP
3
) 236 Hz), 119.8, 120.6, 121.6, 123.3 (d, J ) 13 Hz),
CP
124.7, 125.8, 126.4, 128.3, 128.6, 128.7, 129.5, 130.4, 131.1
3
2
(d, J ) 9 Hz), 132.7 (d, J ) 18 Hz), 136.9, 137.3,
CP
CP
54
43
44
40
>97%
>97%
>97%
>97%
138.1. 31P NMR (161 MHz, CDCl3): δ 10.3. HRMS calcd
for C26H28NO3P: (M + H+) 434.1885, found 434.1881.
2{6}
2{11}
Diethyl 3-Benzyl-2-p-tolyl-2H-isoindol-1-ylphosphonate
a Isolated yield based on 2-alkynylbenzaldehyde 1. b GC analysis.
1
3{1,3}. H NMR (400 MHz, CDCl3): 1.15 (t, J ) 7.2 Hz,
c No product formation was observed. Determined by H NMR.
d
1
6H), 2.42 (s, 3H), 3.82-3.88 (m, 2H), 3.93-3.99 (m, 2 H),
4.12 (s, 2 H), 6.86 (d, J ) 7.6 Hz, 2H), 7.01-7.07 (m, 3H),
7.13-7.25 (m, 6H), 7.54 (dd, J ) 8.4, 0.8 Hz, 1H), 8.15 (d,
to the aromatic core decrease the electrophilicity of the
substrate; resulting in low yields of the desired isoindole.
Additionally, aliphatic amines are not suitable for this
transformation and only aryl substituted acetylene-benzal-
dehydes proved to be effective starting materials in this
reaction. Nevertheless, biological screening of the small
molecules generated here revealed their potential as HCT-
J ) 8.8 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ 16.2, 21.3,
1
31.1, 61.5, 107.7 (d, J ) 233 Hz), 119.7, 120.6, 121.5,
CP
123.2 (d, 3J CP ) 13 Hz), 124.7, 126.2, 128.0, 128.2, 128.3,
3
2
128.9, 131.5 (d, J
) 9 Hz), 132.8 (d, J
) 19 Hz),
CP
CP
135.5, 138.7, 139.1. 31P NMR (161 MHz, CDCl3) δ 10.3.

746 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 5
Yu et al.
HRMS calcd for C26H28NO3P: (M + H+) 434.1885, found
434.1882; (M + Na+) 456.1704, found 456.1697.
C.; Xi, Z. Chem. Soc. ReV. 2007, 36, 1395. (h) Shao, Z.;
Zhang, H. Chem. Soc. ReV. 2009, 38, 2745.
(5) For selected examples, see: (a) Ibrahem, I.; Cordova, A.
Angew. Chem., Int. Ed. 2006, 45, 1952. (b) Bihelovic, F.;
Matovic, R.; Vulovic, B.; Saicic, R. N. Org. Lett. 2007, 9,
5063. (c) Ding, Q.; Wu, J. Org. Lett. 2007, 9, 4959. (d) Binder,
J. T.; Crone, B.; Haug, T. T.; Menz, H.; Kirsch, S. F. Org.
Lett. 2008, 10, 1025. (e) Yang, T.; Ferrali, A.; Campbell, L.;
Dixon, D. J. Chem. Commun. 2008, 2923. (f) Jellerichs, B. G.;
Kong, J.-R.; Krische, M. J. J. Am. Chem. Soc. 2003, 125, 7758.
(g) Cardinal-David, B.; Raup, D. E. A.; Scheidt, K. A. J. Am.
Chem. Soc. 2010, 132, 5345. (h) Lebeuf, R.; Hirano, K.;
Glorius, F. Org. Lett. 2008, 10, 4243. (i) Cernak, T. A.;
Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 3124. (j) Kelly,
B. D.; Allen, J. M.; Tundel, R. E.; Lambert, T. H. Org. Lett.
2009, 11, 1381. (k) Lu, L.-Q.; Cao, Y.-J.; Liu, X.-P.; An, J.;
Yao, C.-J.; Ming, Z.-H.; Xiao, W.-J. J. Am. Chem. Soc. 2008,
130, 6946. (l) Gao, K.; Wu, J. J. Org. Chem. 2007, 72, 8611.
(m) Chen, Z.; Yu, X.; Su, M.; Yang, X.; Wu, J. AdV. Synth.
Catal. 2009, 351, 2702.
Diethyl 3-Benzyl-6-chloro-2-phenyl-2H-isoindol-1-ylphos-
phonate 3{4,1}. H NMR (400 MHz, CDCl3): 1.13 (t, J )
1
7.0 Hz, 6H), 3.80-3.98 (m, 4H), 4.09 (s, 2 H), 6.78-6.80
(m, 2H), 6.97 (dd, J ) 9.2, 1.8 Hz, 1H), 7.12-7.14 (m, 5H),
7.36-7.40 (m, 2H), 7.44-7.49 (m, 2H), 8.18-8.19 (m, 1H).
13C NMR (100 MHz, CDCl3): δ 16.2, 31.2, 61.8, 108.0 (d,
3
1J
) 234 Hz), 119.5, 121.3, 121.6 (d, J
) 13 Hz),
CP
CP
123.1, 126.5, 128.2, 128.3, 128.4, 128.5, 129.4, 130.9, 132.0
3
2
(d, J ) 9 Hz), 133.1 (d, J ) 18 Hz), 137.8, 138.2.
CP
CP
31P NMR (161 MHz, CDCl3): δ 9.8. HRMS calcd for
C25H25ClNO3P: (M + H+) 454.1339, found 454.1325. (For
details, please see Supporting Information.)
Acknowledgment. Financial support from National Natu-
ral Science Foundation of China (20972030) and the Science
& Technology Commission of Shanghai Municipality
(09JC1404902) is gratefully acknowledged. We also thank
Ms. Karinne Van Groningen (Georgetown University) for a
review of the English in our work.
(6) (a) Ding, Q.; Wang, B.; Wu, J. Tetrahedron 2007, 63, 12166.
(b) Sun, W.; Ding, Q.; Sun, X.; Fan, R.; Wu, J. J. Comb.
Chem. 2007, 9, 690.
(7) Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-
VCH Verlag GmbH: Weinheim, Germany, 2000.
Supporting Information Available. Experimental pro-
cedures, characterization data, and 1H and 13C NMR spectra
of compound 3. This material is available free of charge via
the Internet at http://pubs.acs.org.
(8) For reviews, see: (a) Montgomery, J. Angew. Chem., Int. Ed.
2004, 43, 3890. (b) Negishi, E.; Coperet, C.; Ma, S.; Liou,
S. Y.; Liu, F. Chem. ReV. 1996, 96, 365. (c) Tietze, L. F.
Chem. ReV. 1996, 96, 115. (d) Grigg, R.; Sridharan, V. J.
Organomet. Chem. 1999, 576, 65. (e) Miura, T.; Murakami,
M. Chem. Commun. 2007, 217. (f) Malacria, M. Chem. ReV.
1996, 96, 289. (g) Nicolaou, K. C.; Montagnon, T.; Snyder,
S. A. Chem. Commun. 2003, 551. (h) Nicolaou, K. C.;
Edmonds, D. J.; Bulger, P. G. Angew. Chem., Int. Ed. 2006,
45, 7134. (i) Enders, D.; Grondal, C.; Hu¨ttl, M. R. M. Angew.
Chem., Int. Ed. 2007, 46, 1570. (j) Tietze, L. F.; Brasche, G.;
Gericke, K. Domino Reactions in Organic Synthesis; Wiley-
VCH: Weinheim, Germany, 2006. (k) Sun, X.-L.; Tang, Y.
Acc. Chem. Soc. 2008, 41, 937.
References and Notes
(1) (a) Walsh, D. P.; Chang, Y.-T. Chem. ReV. 2006, 106, 2476.
(b) Arya, P.; Chou, D. T. H.; Baek, M.-G. Angew. Chem.,
Int. Ed. 2001, 40, 339. (c) Schreiber, S. L. Science 2000, 287,
1964.
(2) For recent reports on the synthesis and application of isoindole
derivatives, see: (a) Dieltiens, N.; Stevens, C. V. Org. Lett.
2007, 9, 465. (b) Mitsumori, T.; Bendikov, M.; Dautel, O.;
Wudl, F.; Shioya, T.; Sato, H.; Sato, Y. J. Am. Chem. Soc.
2004, 126, 16793. (c) Peng, C.; Cheng, J.; Wang, J. AdV.
Synth. Catal. 2008, 350, 2359. (d) Abdou, W. A.; Kamel,
A. A.; Khidre, M. D. Heteroat. Chem. 2004, 15, 77. (e) Ding,
Q.; Ye, Y.; Fan, R.; Wu, J. J. Org. Chem. 2007, 72, 5439. (f)
Ding, Q.; Wang, B.; Wu, J. Tetrahedron Lett. 2007, 48, 8599.
(3) (a) Phillips, W. G. (Monsanto Co.) Canadian Patent CAN 91:
175521, 1979. (b) Ding, Q.; Li, J.; Wu, J. Manuscript in
preparation (biological results).
(4) For selected recent reviews on multicatalysis, see: (a) Ajamian,
A.; Gleason, J. L. Angew. Chem., Int. Ed. 2004, 43, 3754. (b)
Lee, J. M.; Na, Y.; Han, H.; Chang, S. Chem. Soc. ReV. 2004,
33, 302. (c) Wasilke, J. C.; Brey, O. S. J.; Baker, R. T.; Bazan,
G. C. Chem. ReV. 2005, 105, 1001. (d) Enders, D.; Grondal,
C.; Huttl, M. R. Angew. Chem., Int. Ed. 2007, 46, 1570. (e)
Chapman, C. J.; Frost, C. G. Synthesis 2007, 1. (f) Walji,
A. M.; MacMillan, D. W. C. Synlett. 2007, 1477. (g) Wang,
(9) Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86.
(10) For selected examples, see: (a) Heydari, A.; Javidan, A.;
Shaffie, M. Tetrahedron Lett. 2001, 42, 8071. (b) Saidi, M. R.;
Azizi, N. Synlett 2002, 1347. (c) Ranu, B. C.; Hajra, A.; Jana,
U. Org. Lett. 1999, 1, 1141. (d) Qian, C.; Huang, T. J. Org.
Chem. 1998, 63, 4125. (e) Manabe, K.; Kobayashi, S. Chem.
Commun. 2000, 669. (f) Lee, S.; Park, J. H.; Kang, J.; Lee,
J. K. Chem. Commun. 2001, 1698. (g) Yadav, J. S.; Reddy,
B. V. S.; Madan, C. Synlett 2001, 1131. (h) Joly, G. D.;
Jacobsen, E. N. J. Am. Chem. Soc. 2004, 126, 4102. (i)
Akiyama, T.; Sanada, M.; Fuchibe, K. Synlett 2003, 1463. (j)
Wu, J.; Sun, W.; Wang, W.; Xia, H.-G. Chin. J. Chem. 2006,
24, 1054. (k) Wu, J.; Sun, W.; Sun, X.; Xia, H.-G. Green
Chem. 2006, 8, 365. (l) Wu, J.; Sun, W.; Xia, H.-G.; Sun, X.
Org. Biomol. Chem. 2006, 4, 1663.
CC100101A