Tandem β-enamino ester formation and cyclization with o-alkynyl anilines catalyzed by InBr3: Efficient synthesis of β-(N-Indolyl)-α,β-unsaturated esters

Article abstract of DOI:10.1021/jo802435b

A tandem reaction providing β-(N-indolyl)-α,β-unsaturated esters from β-keto esters and o-alkynyl anilines was developed. Z-Alkenes were selectively formed due to the stability of the β-enamino ester as an intermediate of the reaction. This reaction inclu

Full text of DOI:10.1021/jo802435b

SCHEME 1. Previous Methods
Tandem ꢀ-Enamino Ester Formation and
Cyclization with o-Alkynyl Anilines Catalyzed by
InBr3: Efficient Synthesis of
ꢀ-(N-Indolyl)-r,ꢀ-unsaturated Esters
Kenichi Murai, Shoko Hayashi, Nobuhiro Takaichi,
Yasuyuki Kita,† and Hiromichi Fujioka*
SCHEME 2. Strategy
Graduate School of Pharmaceutical Sciences, Osaka
UniVersity, 1-6 Yamada-oka, Suita, Osaka, 565-0871 Japan
fujioka@phs.osaka-u.ac.jp
ReceiVed NoVember 01, 2008
A tandem reaction providing ꢀ-(N-indolyl)-R,ꢀ-unsaturated
esters from ꢀ-keto esters and o-alkynyl anilines was devel-
oped. Z-Alkenes were selectively formed due to the stability
of the ꢀ-enamino ester as an intermediate of the reaction.
This reaction includes the intermolecular ꢀ-enamino ester
formation and intramolecular cyclization catalyzed by InBr3.
numerous methods for the syntheses of functionalized indoles have
been developed.4 However, there are only a few methods to
synthesize ꢀ-(N-indolyl)-R,ꢀ-unsaturated esters.5,6 Although Michael
addition to alkynoates or the transition metal-catalyzed coupling
reaction with alkenyl iodide or triflate were reported to be syntheses
of these compounds (Scheme 1), they had limitations with the
synthesis of diverse substituted alkenes: R-positions of the products
from alkynoates or alkenyl iodide were limited to being a proton7
and Z alkenes were difficult to obtain from Z-vinyl triflate because
of steric hindrances. Since their synthetic utilities are potentially
interesting,5 to develop an efficient synthetic method for them
having diverse substitutents is desirable.
Our approach for ꢀ-(N-indolyl)-R,ꢀ-unsaturated esters 3 is
illustrated in Scheme 2. Contrary to the reported methods, we
postulated making two C-N bonds (bonds a and b of compound
3) at once by tandem reaction. Thus bond a would be made by
amination of ꢀ-keto esters 2 with o-alkynyl anilines 1, and bond
b would be made by 5-endo-dig intramolecular hydroamination
of ꢀ-enamino ester i.8 This approach was attractive on several
points for making bond a: the formation of ꢀ-enamino ester
The development of novel tandem reactions is important
because they can easily provide complex molecules, simplify
the procedures, and reduce the waste.1 They generally include
several catalytic cycles. When several functional groups were
activated by a catalyst, it was necessary not only to promote
each step but also to activate each functional group in order.2
During the course of our research for efficient methods for
heterocyclic compounds using ꢀ-enamino esters,3 we examined
the reaction of ꢀ-enamino esters prepared from ꢀ-keto esters
and o-alkynyl anilines and found that InBr3 promotes two
reactions, intermolecular amination and subsequent intramo-
lecular cyclization, at once and activates the formation of the
ꢀ-enamino esters faster than the intramolecular cyclization. We
now report a tandem reaction to provide diverse Z-ꢀ-(N-indolyl)-
R,ꢀ-unsaturated esters.
(4) For a review, see: Humphrey, G. R.; Kuethe, J. T. Chem. ReV. 2006,
106, 2875–2911, and references cited therein.
(5) (a) Raboisson, P.; Manthey, C. L.; Chaikin, M.; Lattanze, J.; Crysler, C.;
Leonard, K.; Pan, W.; Tomczuk, B. E.; Maruga´n, J. J. Eur. J. Med. Chem. 2006,
41, 847–861. (b) Leonard, K.; Pan, W.; Anaclerio, B.; Gushue, J. M.; Guo, Z.;
DesJarlais, R. L.; Chaikin, M. A.; Lattanze, J.; Crysler, C.; Manthey, C. L.;
Tomczuk, B. E.; Marugan, J. J. Bioorg. Med. Chem. Lett. 2005, 15, 2679–2684.
(c) Rainka, M. P.; Aye, Y.; Buchwald, S. L. Proc. Natl. Acad. Sci. U.S.A. 2004,
101, 5821–5823.
(6) Movassaghi, M.; Ondrus, A. E. J. Org. Chem. 2005, 70, 8638–8641.
(7) ꢀ-Iodo-R,ꢀ-unsaturated esters were generally prepared from alkynoates.
For examples, see: (a) Maguire, R. J.; Munt, S. P.; Thomas, E. J. J. Chem. Soc.,
Perkin Trans. 1 1998, 2853–2863. (b) Dieter, R. K.; Lu, K. J. Org. Chem. 2002,
67, 847–855.
Indoles are some of the most important heterocycles because
they are found in various biologically active compounds, and
† Present address: College of Pharmaceutical Sciences, Ritsumeikan Univer-
sity, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577 Japan.
(1) For reviews about tandem reactions, see: (a) Chapman, C. J.; Frost, C. G.
Synthesis 2007, 1–21. (b) Wasilke, J.-C.; Obrey, S. J.; Baker, R. T.; Bazan, G. C.
Chem. ReV. 2005, 105, 1001–1020.
(2) For a review, see: (a) Yamamoto, Y. J. Org. Chem. 2007, 72, 7817–
7831.
(3) (a) Fujioka, H.; Murai, K.; Kubo, O.; Ohba, Y.; Kita, Y. Org. Lett. 2007,
9, 1687–1690. (b) Murai, K.; Nakatani, R.; Kita, Y.; Fujioka, H. Tetrahedron
2008, 64, 11034–11040.
(8) For a gold-catalyzed tandem double hydroamination of o-alkynyl aniline
with terminal alkynes providing N-vinyl indoles, see: Zhang, Y.; Donahue, J. P.;
Li, C. J. Org. Lett. 2007, 9, 627–630.
1418 J. Org. Chem. 2009, 74, 1418–1421
10.1021/jo802435b CCC: $40.75 2009 American Chemical Society
Published on Web 12/29/2008

TABLE 1. Optimizationa
seemed to be relatively easier than previous methods and diverse
ꢀ-ketoesters were available. In addition, the theoretical coproduct
of this process was only water. Furthermore, due to the stability
of hydrogen bonding of the ꢀ-enamino ester, the geometries of
alkenes were expected to be Z.
Although each individual reaction of the ꢀ-enamino ester
formation9 and catalytic intramolecular hydroamination of
o-alkynyl aniline derivatives10 was well documented, there were
no reports of what caused the two reactions at once. In addition,
to the best of our knowledge, no intramolecular cyclization
reaction of ꢀ-enamino esters prepared from o-alkynyl aniline
to give indole derivatives has been reported yet. For the success
of our aim, the chemoselectivity (ꢀ-keto esters vs alkynes) of
the catalyst was very important. When the affinity of the catalyst
to alkynes was much stronger than that to ꢀ-keto esters,
intramolecular hydroamination of 1 would predominantly occur
to afford indole 4 and the desired tandem reaction would fail.11
Therefore, to achieve this tandem reaction, it was very important
to find a catalyst that promotes both intermolecular amination
of the ꢀ-keto esters 2 and subsequent intramolecular cyclization
of ꢀ-enamino ester i in order. On the other hand, from the
viewpoint of reactivity of ꢀ-enamino esters, their R-carbons were
also nucleophilic.12,13 Then two reaction pathways from i,
5-endo-dig cyclization giving indole derivatives 3 and 6-exo-
dig cyclization giving quinoline derivatives 5, were possible.
Therefore, the mode of cyclization of i was also of interest.
We first screened the catalysts using the o-alkynyl aniline
1a and ꢀ-keto ester 2a (Table 1). When NaAuCl4 ·2H2O was
entry
catalyst
time
yield (3a, 4a) (%)b
1
2
3
4
5
6
7
8f
NaAuCl4 ·2H2O
Cu(OAc)2
AgBF4
Yb(OTf)3
InBr3
InCl3
In(OTf)3
InBr3
20 min
6 h
3.5 h
85 (34, 51)
N.D.c
N.D.d
5.5 h
N.D.e
30 min
30 min
2.7 h
91 (82, 9)
83 (78, 5)
24 (23, 1)
99 (91, 8)
30 min
a Reaction was carried out with 0.4 mmol of 1a. b Ratio was
determined by 1H NMR analysis. c Main product was amide 6. d Main
product was enamino ester 7. e Main products were amide 6 and
enamino ester 7. f 0.05 equiv of InBr3 was used.
used, the desired product 3a was obtained in only 34% yield,
and 2-Ph indole 4a, which was the cyclized product of 1a, was
the predominant produced (entry 1). Other metals such as
Cu(OAc)2, AgBF4, and Yb(OTf)3 were found to be ineffective
(entries 2-4). The reaction with Cu(OAc)2 produced the ꢀ-keto
amide 6. The reactions with AgBF4 or Yb(OTf)3 produced the
ꢀ-enamino ester 7 but did not allow the sequential intramolecular
cyclization. On the other hand, InBr3 was found to be an efficient
catalyst in this tandem reaction, which resulted in a good yield
and selectivity (entry 5).14 Although InCl3 was also efficient
and a high selectivity was observed, the yields were slightly
low because of the side production of 6 (entry 6). Reaction with
In(OTf)3 resulted in low yield (entry 7). To our surprise, 6-exo-
dig cyclization of enamino ester to affrod quinoline derivative
5 was not observed in this reaction. As a result of the further
optimization, it was found that the reaction carried out with the
ꢀ-keto ester (1.3 equiv) and InBr3 (0.05 equiv) in refluxing
toluene (0.3 M) gave the best result (entry 8).15
(9) For recent examples, see: (a) Arcadi, A.; Bianchi, G.; Giuseppe, S. D.;
Marinelli, F. Green Chem. 2003, 5, 64–67. (b) Brandt, C. A.; Da Silva,
A. C. M. P.; Pancote, C. G.; Brito, C. L.; Da Silveira, M. A. B. Synthesis 2004,
1557–1559. (c) Stefane, B.; Polanc, S. Synlett 2004, 698–702. (d) Gao, Y.-H.;
Zhang, Q.-H.; Xu, J.-X. Synth. Commun. 2004, 34, 909–916. (e) Bartoli, G.;
Bosco, M.; Locatelli, M.; Marcantoni, E.; Melchiorre, P.; Sambri, L. Synlett
2004, 239–242. (f) Varala, R.; Nuvula, S.; Adapa, S. R. Aust. J. Chem. 2006,
59, 921924 (g) For InBr3-catalyzed formation of ꢀ-enamino esters, see: (h) Zhang,
Z.-H.; Yin, L.; Wang, Y.-M. AdV. Synth. Catal. 2006, 348, 184–190, and
references cited therein.
(10) For selected reviews and papers, see: (a) Cacchi, S.; Fabrizi, G. Chem.
ReV. 2005, 105, 2873–2920. (b) Takeda, A.; Kamijo, S.; Yamamoto, Y. J. Am.
Chem. Soc. 2000, 122, 5662–5663. (c) Hiroya, K.; Itoh, S.; Sakamoto, T. J.
Org. Chem. 2004, 69, 1126–1136. (d) Ohno, H.; Ohta, Y.; Oishi, S.; Fujii, N.
Angew. Chem., Int. Ed. 2007, 46, 2295–2298. (e) Alfonsi, M; Arcadi, A.; Aschi,
M.; Bianchi, G.; Marinelli, F. J. Org. Chem. 2005, 70, 2265–2273. (f) Li, X.;
Chianese, A. R.; Vogel, T.; Crabtree, R. H. Org. Lett. 2005, 7, 5437–5440. (g)
Trost, B. M.; McClory, A. Angew. Chem., Int. Ed. 2007, 46, 2074–2077. (h)
Shimada, T.; Nakamura, I.; Yamamoto, Y. J. Am. Chem. Soc. 2004, 126, 10546–
10547. (i) McDonald, F. E.; Chatterjee, A. K. Tetrahedron Lett. 1997, 38, 7687–
7690. (j) Kurisaki, T.; Naniwa, T.; Yamamoto, H.; Imagawa, H.; Nishizawa, M.
Tetrahedron Lett. 2007, 48, 1871–1874. (k) Kusama, H.; Takaya, J.; Iwasawa,
N. J. Am. Chem. Soc. 2002, 124, 11592–11593. (l) Rodriguez, A. L.; Koradin,
C.; Dohle, W.; Knochel, P. Angew. Chem., Int. Ed. 2000, 39, 2488–2490. (m)
Koradin, C.; Dohle, W.; Rodriguez, A. L.; Schmid, B.; Knochel, P. Tetrahedron
2003, 59, 1571–1587. (n) McLaughlin, M.; Palucki, M.; Davies, I. W. Org. Lett.
2006, 8, 3307–3310. (o) Yin, Y.; Ma, W.; Chai, Z.; Zhao, G. J. Org. Chem.
2007, 72, 5731–5736. For InBr3-catalyzed cyclization of o-alkynyl anilines, see:
(p) Sakai, N.; Annaka, K.; Fujit, A.; Sato, A.; Konakahara, T. J. Org. Chem.
2008, 73, 4160–4165. (q) Sakai, N.; Annaka, K.; Konakahara, T. Tetrahedron
Lett. 2006, 47, 631–634. (r) Sakai, N.; Annaka, K.; Konakahara, T. Org. Lett.
2004, 6, 1527–1530. (s) Sakai, N.; Annaka, K.; Konakahara, T. J. Org. Chem.
2006, 71, 3653–3655.
(11) For a tandem reaction with o-alkynyl anilines and 1,3-dicarbonyl
compounds with a gold catalyst providing 3-alkenyl indoles through intramo-
lecular hydroamination and sequential alkenylation, see: Arcadi, A.; Alfonsi, M.;
Bianchi, G.; D’Anniballe, G.; Marinelli, F. AdV. Synth. Catal. 2006, 348, 331–
338.
(12) For reviews, see: (a) Stanovnik, B.; Svete, J. Chem. ReV. 2004, 104,
2433–2480. (b) Elassar, A.-Z. A.; El-Khair, A. A. Tetrahedron 2003, 59, 8463–
8480.
(13) For reactions of ꢀ-enamino esters having alkynes, see: (a) Cacchi, S.;
Fabrizi, G.; Filisti, E. Org. Lett. 2008, 10, 2629–2632. (b) Arcadi, A.; Giuseppe,
S. D.; Marinelli, F.; Rossi, E. Tetrahedron: Asymmetry 2001, 12, 2715–2720.
(c) Robinson, R. S.; Dovey, M. C.; Gravestock, D. Tetrahedron Lett. 2004, 45,
6787–6789. (d) Arcadi, A.; Giuseppe, D. G.; Marinelli, F.; Rossi, E. AdV. Synth.
Catal. 2001, 343, 443–446.
To confirm the reaction pathway, the reaction of 4a and 2a
with InBr3 in refluxing toluene was carried out. However, 3a
was not obtained even after 16 h. This fact excluded the tandem
cyclization/enamino ester formation pathway. Meanwhile, the
reaction of 7 with InBr3 afforded 3a in 92% yield. Therefore,
this tandem reaction was considered to proceed through the
following sequence: (1) the activation of the ꢀ-keto esters, (2)
(14) For selected reviews and papers about indium-catalyzed reactions, see: (a)
Auge´, J.; Lubin-Germain, N.; Uziel, J. Synthesis 2007, 1739–1764. (b) Loh, T.-P.;
Chua, G.-L. Chem. Commun. 2006, 2739–2749. (c) Takahashi, K.; Midori, M.;
Kawano, K.; Ishihara, J.; Hatakeyama, S. Angew. Chem., Int. Ed. 2008, 47, 6244–
6246. (d) Kawata, A.; Takata, K.; Kuninobu, Y.; Takai, K. Angew. Chem., Int.
Ed. 2007, 46, 7793–7795. (e) Obika, S.; Kono, H.; Yasui, Y.; Yanada, R.;
Takemoto, Y. J. Org. Chem. 2007, 72, 4462–4468. (f) Endo, K.; Hatakeyama,
T.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc. 2007, 129, 5264–5271. (g)
Takita, R.; Fukuta, Y.; Tsuji, R.; Ohshima, T.; Shibasaki, M. Org. Lett. 2005, 7,
1363–1366. (h) Nakamura, M.; Endo, K.; Nakamura, E. J. Am. Chem. Soc. 2003,
125, 13002–13003. (i) Yasuda, M.; Onishi, Y.; Ueba, M.; Miyai, T.; Baba, A.
J. Org. Chem. 2001, 66, 7741–7744, and references cited therein.
(15) One reviewer suggested that the reaction of ꢀ-keto ester (1.0 equiv)
and slight excess of o-alkynyl aniline (1.3 equiv) should be carried out. The
reaction of 2a (1.0 equiv) and 1a (1.3 equiv) with InBr3 (0.05 equiv) yielded 3a
(75%) and 4a (21%) (yields were based on 1a).
J. Org. Chem. Vol. 74, No. 3, 2009 1419

TABLE 2. Reactions with Various ꢀ-Keto Estersa,b
TABLE 3. Reactions with Various o-Alkynyl Anilines and 2ia b
,
entry
R
time
yield (%)
1c
2c
3d
4d
5c
p-Cl-C6H4 (1b)
p-MeO-C6H4 (1c)
n-Bu (1d)
cyclohexyl (1e)
cyclohexenyl (1f)
20 min
1 h
24 h
24 h
1 h
3j, 94
3k, 84
3l, 67
3m, 70
3n, 67
a Reaction was carried out with 0.4 mmol of 1a. b Starting materials
were completely consumed in every entry (judged by TLC). c 0.05 equiv
of InBr3 was used. d 0.15 equiv of InBr3 was used.
FIGURE 1. Products from simple ketones.
as these results, the developed reaction readily provided
R-substituted R,ꢀ-unsaturated esters that were difficult to obtain
with the reported methods. Furthermore, as we expected, the
geometries of the products were completely controlled and every
product was the Z-alkene.16
We next examined the reactions with various o-alkynyl
anilines and ꢀ-keto ester 2i (Table 3). Substituent effects on
the para position of the phenyl group were first examined and
it was found that both the electron-withdrawing Cl group and
the electron-donating MeO group were applicable (entries 1 and
2). The substrates having an n-butyl and cyclohexyl gave
moderate yields (entries 3 and 4), though 0.15 equiv of InBr3
and a long reaction time were necessary. Furthermore, a
substrate having a cyclohexenyl group, whose olefin could be
transformed into various functional groups, was tolerant (67%,
entry 5).17
Lastly, to compare the reactivity between the ꢀ-keto esters
and simple ketones, 4-heptanone and o-alkynyl aniline 1a were
subjected to the optimized reaction conditions. Although the
tandem reaction occurred, the yield of the desired 3o was only
24% and the major product was indole 4a (see Table 1).
Therefore, the 1,3-dicarbonyl structures were considered to be
important for good yield probably due to the high affinity to
InBr3 or to stabilize the enamine structures of the intermediates
or the products. In addition, interestingly, 3o (Figure 1) was
formed E-selectively. This result showed a good contrast to the
result with ꢀ-keto esters, which prefered Z-selectivity due to
the intramolecular hydrogen bonding of ꢀ-enamino esters. On
the other hand, the reaction with acetophenone produced the
desired compound 3p in 66% yield. Furthermore, the reaction
with cyclopentanone produced compound 3q in high yield
(93%). These results showed that the developed tandem reaction
could be expanded to N-vinyl indole syntheses18 by using
a Reaction was carried out with 0.4 mmol of 1a unless otherwise
noted. b Starting materials were completely consumed in every entry
(judged by TLC). c 3.8 mmol of 1a was used.
formation of ꢀ-enamino esters, and (3) intramolecular cyclization
promoted by activation of the acetylene.
Under the optimized reaction conditions, the generality of
the reaction with various ꢀ-keto esters was examined (Table
2). The reactions with methyl, benzyl, and isopropyl acetoacetate
(2a-c), which each gave good results (entries 1-3). The
reaction with tert-butyl acetoacetate 2d decreased the yield
(entry 4) probably due to the acid-sensitive tert-butyl ester, while
the allyl acetoacetate 2e resulted in a moderate yield (entry 5).
Various ꢀ-keto esters having substitutions on their R and/or γ
positions were next examined. The use of methyl propionylac-
etate 2f resulted in a 71% yield (entry 6). The use of ethyl
2-methyl acetoacetate 2g also gave a moderate result (entry 7).
ꢀ-Keto esters having a lactone ring, R-acetylbutyrolactone 2h,
and a cyclic ketone, ethyl 2-oxocyclopentanecarboxylate 2i, both
resulted in good yields (entries 8 and 9). The reaction with 3.8
mmol of 1a also proceeded without any problems and the gram
amount of 3i was obtained in 94% yield (entry 10). As shown
(16) Determined by NOE analysis.
(17) Unfortunately, the reaction with o-ethynyl aniline afforded complex
mixtures including an enamino ester bearing a teminal alkyne such as 7 and a
quinoline delivative by the dimerization of o-ethynyl aniline (for the dimerization
of o-ethynyl aniline, see ref 10s).
(18) Only a few methods for the synthesis of N-vinyl indoles were reported.
References are ceited in ref 8.
1420 J. Org. Chem. Vol. 74, No. 3, 2009

reaction mixture was heated under reflux. After 30 min, the reaction
mixture was cooled to rt, quenched with water, and extracted with
AcOEt. The organic phase was washed with sat. NaCl aq, dried
over Na2SO4, and concentrated in vacuo. The residue was purified
by SiO2 column chromatography (two purifications: first eluent,
hexane/AcOEt ) 10/1; second eluent, benzene/hexane ) 1/1) to
afford 3a. Colorless oil; 1H NMR (300 MHz, CDCl3) δ 7.63-7.56
(m, 3H), 7.44-7.32 (m, 3H), 7.20-7.11 (m, 3H), 6.74 (s, 1H),
6.17 (s, 1H), 3.49 (s, 3H), 1.89 ppm (d, J ) 0.9 Hz, 3H); 13C NMR
(75.5 MHz, CDCl3) δ 164.5, 148.2, 139.6, 137.1, 132.9, 128.8,
128.6, 127.88, 127.85, 122.5, 120.7 (2C), 118.1, 110.2, 104.6, 51.5,
various ketones in place of ꢀ-keto esters, though further
optimizations would be necessary.
In conclusion, we have developed a novel tandem reaction
providing diverse Z-ꢀ-(N-indolyl)-R,ꢀ-unsaturated esters from
readily available ꢀ-keto esters and o-alkynyl anilines. This
approach is very effective and the generality is high and can
provide R-substituted anilines, which were difficult to prepare
with the previous methods. The finding that InBr3 promotes two
reactions of intermolecular amination and subsequent intramo-
lecular cyclization at once and activates formation of the
ꢀ-enamino esters faster than the intramolecular cyclization is
very interesting. In addition, this is the first example of the
reaction of o-alkynyl anilines having ꢀ-enamino ester structures
and it was found that 5-endo-dig cyclization proceeded rather
than 6-exo-dig cyclization. Further investigations for N-vinyl
indoles, clarification of the difference between ꢀ-keto esters and
simple ketones, and synthesis of biologically active compounds
are underway.
24.0 ppm; IR (KBr) 3059, 2949, 1732, 1661, 1454, 1213 cm-1
;
HRMS (FAB) calcd for C19H17NO2Na [M + Na]+ 314.1157, found
314.1157. Anal. Calcd for C19H17NO2: C, 78.33; H, 5.88; N, 4.81.
Found: C, 78.29; H, 6.01; N, 4.77.
Acknowledgment. We are grateful to Dr. Kotoku, N. for his
help with NMR measurement. This work was financially
supported by a Grant-in-Aid for Scientific Research (A) and
(B) and a Grant-in-Aid for Exploratory Research from Japan
Society for the Promotion of Science.
Experimental Section
Supporting Information Available: Experimental details and
detailed spectroscopic data of all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
Representative Procedure for the Tandem Reaction.
Compound 3a. InBr3 (7.3 mg, 0.021 mmol) was added to a solution
of o-alkynyl aniline 1a (80.0 mg, 0.414 mmol) and ꢀ-keto ester 2a
(58 µL, 0.538 mmol) in toluene (1.38 mL) at rt under N2. The
JO802435B
J. Org. Chem. Vol. 74, No. 3, 2009 1421