Synthesis of functionalized indoles with an α-stereogenic ketone moiety through an enantioselective friedel-crafts alkylation with (E)-1,4-Diaryl-2-butene-1,4-diones

Article abstract of DOI:10.1002/adsc.200900357

Chiral complexes of BINOL-based ligands with hafnium tert-butoxide catalyze the enantioselective Friedel-Crafts alkylation of indoles with (E)-1,4diaryl-2-butene-1,4-diones at room temperature, with good yields and ee up to 94%. Hafnium(IV) was found to b

Full text of DOI:10.1002/adsc.200900357

FULL PAPERS
DOI: 10.1002/adsc.200900357
Synthesis of Functionalized Indoles with an a-Stereogenic Ketone
Moiety Through an Enantioselective Friedel–Crafts Alkylation
with (E)-1,4-Diaryl-2-butene-1,4-diones
Gonzalo Blay,a Isabel Fernꢀndez,a Alicia Monleꢁn,a M. Carmen MuÇoz,b
Josꢂ R. Pedro,a,* and Carlos Vilaa
a
Departament de Quꢃmica Orgꢄnica, Facultat de Quꢃmica, Universitat de Valꢅncia, C/Dr. Moliner, 50, 46100 Burjassot
(Valꢅncia), Spain
Fax : (+34)-96-354-4328; phone: (+34)-96-354-4336; e-mail: jose.r.pedro@uv.es
Departamento de Fꢃsica Aplicada, Universidad Politꢂcnica de Valencia, 46071 Valꢅncia, Spain
b
Received: May 21, 2009; Revised: July 31, 2009; Published online: September 23, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900357.
Abstract: Chiral complexes of BINOL-based ligands here generates an a-stereogenic center with respect
with hafnium tert-butoxide catalyze the enantioselec- to one of the carbonyl groups. This can be regarded
tive Friedel–Crafts alkylation of indoles with (E)-1,4- as an inversion of the normal reactivity pattern or
diaryl-2-butene-1,4-diones at room temperature, with umpolung. The enantioselective Friedel–Crafts alky-
good yields and ee up to 94%. Hafnium(IV) was lation of indoles with (E)-4-oxo-4-phenylbutenoates
found to be a more effective Lewis acid than other using a zirconium(IV)-BINOL catalyst is also report-
frequently used metal ions such as titanium(IV) or ed. This reaction takes place regioselectively at the
zirconium(IV). Unlike the enantioselective Friedel– carbon in the b-position to the ketone carbonyl
Crafts alkylation of indoles with a,b-unsaturated group, generating an a-ester stereogenic center.
compounds where the stereogenic center is generat-
ed in the b-position to a carbonyl group, the Friedel– Keywords: asymmetric catalysis; enones; hafnium; O
Crafts alkylation with 2-butene-1,4-diones described ligands; umpolung; zirconium
Introduction
merically enriched indoles is of great interest for the
development of new synthetic strategies toward drugs
The indole nucleus is present in a large number of and bioactive compounds.
compounds of biological and/or pharmaceutical inter-
In this paper, we describe the enantioselective Frie-
est.[1] Because of this, chemical methods for its synthe- del–Crafts reaction of indoles 1 with (E)-1,4-diaryl-2-
sis have been developed for more than a hundred butene-1,4-diones 2 as a new convenient procedure to
years. In the last years, several catalytic system based functionalize the C-3 position of indoles with a side
on metal catalysis or organocatalysis have been devel- chain bearing a 1,4-dicarbonyl moiety and a stereo-
oped and successfully applied to the enantioselective genic center. While the Friedel–Crafts alkylations
Friedel–Crafts alkylation of indoles with prochiral un- with a,b-unsaturated substrates through a conjugate
saturated compounds as electrophiles leading to enan- addition result in the formation of a stereogenic
tiomerically enriched alkylated indoles.[2] To date, center in the b-position to a carbonyl group, the reac-
most of the successful examples of such processes tion with 2-butene-1,4-diones generates an a-stereo-
have been limited to the use of bidentate chelating genic center with respect to one of the carbonyl
carbonyl substrates[3–13] and nitroalkenes,[14] whereas groups. According to Tan,[17] as this a-stereogenic
the use of non.chelating electrophilic substrates still center is obtained through the action of a nucleophile
remains rare and limited to structurally simple mono- (the indole nucleus) on an unsaturated ketone, this
functional a,b-unsaturated aldehydes[15] and enones.[16] can be considered as an inversion of the normal reac-
The study of new electrophilic partners for the enan- tivity pattern or umpolung reactivity[18] (Scheme 1).
tioselective Friedel–Crafts reaction that can provide
To date, only two reports on asymmetric nucleo-
access to a broader range of functionalized enantio- philic additions (Michael reactions) to 1,4-dicarbonyl-
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Scheme 2. Friedel–Crafts alkylation of indoles 1 with (E)-
1,4-diaryl-2-butene-1,4-diones 2.
Scheme 1. Friedel–Crafts alkylation of indole with enones
and enediones.
but-2-enes have been published;[17,19] one of them in-
volving arylboronic acids and the other 1,3-dicarbonyl
compounds as nucleophiles, while the Friedel–Crafts
reaction of nucleophilic heterocycles with this kind of
acceptors has not been described so far. (E)-1,4-
Diaryl-2-butene-1,4-diones 2 are challenging sub-
strates on account of their functionalization with two
carbonyl groups conjugate to a common trans-double
bond. Because of these structural features it is expect-
ed that compounds 2 acts as non-chelating substrates,
Figure 1. Structure of BINOL-type ligands used in this
study.
A number of BINOL-type ligands (L1–L2 and L4–
similarly to simple a,b-unsaturated ketones, but with L5), which contained electron-withdrawing groups
reduced reactivity toward nucleophiles.[20]
and/or a tetrahydrogenated ring, were then screened
(Figure 1).[22] Ligand L2 gave the best result providing
3aa in 89% yield and 69% ee (entry 2). A further im-
provement on the yield and reaction rate was ob-
tained when dioxane was used as the solvent
Results and Discussion
In a recent paper we reported the enantioselective (entry 8); toluene and diethyl ether (entries 6 and 7)
Friedel–Crafts reaction of indoles with simple a,b-un- also increased the reaction rate but gave lower enan-
saturated ketones catalyzed by a chiral BINOL- tioselectivities than dichloromethane.
Zr(IV) complex.[21] This reaction was achieved with
Other metal alkoxides[23] were also tested with L2
good yields and high enantioselectivities. Therefore, in dioxane. In the presence of TiACTHNUTRGENUG(N i-PrO)4 (entry 10)
we intended to use this catalytic system in the reac- the reaction took place slowly and compound 3aa was
tion of indoles 1 with enediones 2 (Scheme 2). First, obtained in low yield (32%) and with low ee (44%)
we applied our previously optimized reaction condi- while HfACTHNUGRTNENUG(t-BuO)4 gave a similar reactivity as ZrACHTUNGTRENNUNG(t-
tions to the Friedel–Crafts reaction of indole (1a) BuO)4, but the product 3aa was obtained with some-
with (E)-1,4-diphenyl-2-butene-1,4-dione (2a) using how higher ee (73%) (entry 9).
ligand L3 (Figure 1) and Zr
G
Our efforts to optimize the reaction conditions
thane at room temperature. As anticipated, the reac- were also aimed at exploring the effectiveness of Hf-
tion of 1a with 2a was slow and required 20 h to go to
ACHTUNGTERN(NUNG t-BuO)4 in the presence of alcohols with different
completion, much longer than the time required (3 h) chain lengths as additives.[24] After some experimenta-
for the reaction of 1a and the enone (E)-1-phenyl-2- tion we found that an 80 mol% amount of alcohol
buten-1-one in our previous work.[21] The resulting with respect to the enedione brought about an impor-
product 3aa was obtained in moderate 59% yield and tant increase of enantioselectivity. In general, we did
with low enantioselectivity (23% ee) (Table 1, not find a big influence of the alcohol chain length on
entry 3).
the enantioselectivity, although it affected the yield of
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Synthesis of Functionalized Indoles with an a-Stereogenic Ketone Moiety
FULL PAPERS
Table 1. Screening of ligands, metal alkoxides, solvents and additives for the Friedel–Crafts reaction of 1a (R1 =R2 =R3 =
R4 =H) and 2a (Ar=Ph) according to Scheme 2.[a]
Entry
M(RO)4
Zr(t-BuO)4
L
Solvent
Additive
t [h]
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
G
L1
L2
L3
L4
L5
L2
L2
L2
L2
L2
L2
L2
L2
L2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
Toluene
Et2O
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
–
–
–
–
–
–
–
–
20
16
20
18
22
3
3.5
4
3.3
46
22
3
93
89
59
84
45
84
68
99
87
32
59
92
74
93
57
69
Zr(t-BuO)4
Zr(t-BuO)4
Zr(t-BuO)4
Zr(t-BuO)4
Zr(t-BuO)4
Zr(t-BuO)4
Zr(t-BuO)4
Hf(t-BuO)4
Ti(i-PrO)4
Hf(t-BuO)4
Hf(t-BuO)4
Hf(t-BuO)4
Hf(t-BuO)4
T
E
T
N
N
R
N
À23[d}
À17[d]
19
42
50
69
73
44
88
87
83
9
R
–
–
10
11
12
13
14
T
N
R
T
N
EtOH
n-PrOH
n-BuOH
i-BuOH
5
2.5
85
[a]
Conditions: 1a (0.30 mmol), 2a (0.25 mmol), M(RO)4 (0.05 mmol), L (0.05 mmol), solvent (2 mL), additive (0.2 mmol),
room temperature.
Isolated yield of 3aa.
Determined by chiral HPLC.
The opposite enantiomer was obtained.
[b]
[c]
[d]
the reaction. The best result was obtained with yields (74–92%) and with high enantioselectivities
80 mol% n-propanol that allowed obtaining product (85–90% ee). Unfortunately, neither the heteroaro-
3aa in 92% yield and 87% ee (entry 12).
To explore the scope and potential of the reaction, 2g (entry 14) reacted under the optimized conditions.
various 1,4-diaryl-2-butene-1,4-diones 2 containing The indole partner was also amenable to modifica-
matic enedione 2f (entry 6) nor the aliphatic enedione
electron-donating or electron-withdrawing groups on tion. A number of C-5-substituted indoles were react-
the phenyl group were reacted with indole (1a) ed with endione 2a (entries 7–9). In general, the enan-
(Table 2, entries 1–5). In all cases the corresponding tioselectivity of the reaction did not show a big de-
alkylated products 3 were obtained in very good pendence on the electronic features of the substituent,
Table 2. Enantioselective Friedel–Crafts reaction of indoles 1 and endiones 2 catalyzed by Hf
ACHTUNGTNER(NUGN t-BuO)4 and L2 according to
Scheme 2.[a]
Entry
1
R1
R2
R3
R4
2
Ar
t [h]
3
Yield [%][b]
ee [%][c]
1
2
1a
1a
1a
1a
1a
1a
1b
1c
1d
1d
1e
1f
1g
1a
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
Me
MeO
Br
Br
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
2a
2b
2c
2d
2e
2f
2a
2a
2a
2b
2a
2a
2a
2g
Ph
3
22
3
5
7
3aa
3ab
3ac
3ad
3ae
92
74
88
87
81
n.r.
90
91
76
88
91
92
97
n.r.
87
90
90
85
86
p-MeC6H4
3,4-Me2C5H3
p-MeOC6H4
p-FC6H4
2-thienyl
Ph
Ph
Ph
p-MeC6H4
Ph
Ph
3[d]
4[d]
5
6
7
8
9
3
6
24
5
5
3ba
3ca
3da
3db
3ea
3fa
3ga
88
87
93
94
85
69
86
10[d]
11
12
13
14
5
3
Ph
Me
[a]
n
Conditions: 1 (0.30 mmol), 2 (0.25 mmol), Hf
room temperature.
Isolated yield of 3.
(tBuO)4 (0.05 mmol), L2 (0.05 mmol), dioxane (2 mL), PrOH (0.2 mmol),
[b]
[c]
[d]
Major (S)-enantiomer. Determined by chiral HPLC.
40 mol% L2 and 40 mol% Hf(t-BuO)4 was used.
AHCTUNGTRENNUNG
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although the presence of the electron-withdrawing Br
atom at the 5-position of indole decreased the reac-
tion rate (entries 9 and 10). Also, 7-methylindole (1e)
reacted with 2a to give 3ea (entry 11) in high yield
and good ee (85%). However, the presence of a
methyl group at the C-2 position (entry 12) brought
about a decrease in the ee, compound 3fa being ob-
tained with only 69% ee, although in good yield
(92%). Finally, 1-methylindole (1g), having a substi-
tuted nitrogen atom, reacted almost quantitatively
(entry 13) with 2a to give 3ga with high enantioselec-
tivity (86% ee). This result is remarkable since, in our
previous work, we found that 1-methylindole (1g) re-
acted with (E)-1-phenyl-2-buten-1-one under catalysis
with the L3-Zr(IV) system to give an almost racemic
product.[25]
Scheme 4. Friedel–Crafts alkylation of indoles (1) with alkyl
(E)-4-oxo-4-phenylbutenoates 6.
Considering the synthetic value of pyrroles, we
have also studied the reaction of pyrrole (4) with (E)-4-oxo-4-arylbutenoates 6, which will generate a-
compound 2a under the optimized conditions for in- ester stereogenic centers (Scheme 4). However, under
doles (Scheme 3). The alkylated pyrrole 5 was thus the optimized conditions for enediones, ethyl (E)-4-
obtained in almost quantitative yield and in moderate oxo-4-phenylbutenoate (6a) did not react with indole
ee (66%) after 1 h of reaction at room temperature.
(1a). In spite of this, the reaction could be carried out
(t-BuO)4/L3 in dichloromethane in the ab-
Finally, we tried to expand the scope of our catalyt- with ZrAHCTUNGTRENNUNG
ic system to other 1,4-dicarbonyl-but-2-enes such as sence of an alcohol additive (conditions of entry 3 in
Table 1). Under these conditions, ethyl (E)-4-oxo-4-
phenylbutenoate (6a) reacted with indole (1a) to give
compound 7aa as the sole product in 50% yield and
79% ee (Table 3, entry 1). Although the yield was
moderate, the reaction took place with fair enantiose-
lectivity and total regioselectivity, the only product
being observed was that derived from the b-attack of
the indole to the enone moiety present in the starting
material, so generating an a-ester stereogenic center.
A further improvement could be achieved by chang-
ing the ester group. Thus, the reaction of indole (1a)
with methyl ester 6b provided the Friedel–Crafts
product 7ab in 80% yield with a high 93% ee. Other
5-substituted indoles reacted with 6b to give the cor-
responding products 7bb and 7cb with high enantiose-
lectivity (entries 5 and 6), while indoles 1e and 1f
Scheme 3. Friedel–Crafts alkylation of pyrrole 4 with (E)-
1,4-diphenyl-2-butene-1,4-dione 2a.
Table 3. Enantioselective Friedel-Crafts reaction of indoles 1 and alkyl (E)-4-oxo-4-phenylbutenoates 6 catalyzed by Zr
BuO)4 and L3 according to Scheme 4.[a]
ACHTUNGTRENNUNG(t-
Entry
1
R1
R2
R3
R4
6
R5
t [h]
7
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1b
1c
1e
1f
1g
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
Me
H
H
H
H
H
Me
MeO
H
H
H
H
H
H
H
H
H
Me
H
H
6a
6b
6c
6d
6b
6b
6b
6b
6b
Et
22
4
7
18
8
7
10
7
24
7aa
7ab
7ac
7ad
7bb
7cb
7eb
7fb
7gb
50
80
88
35
56
84
67
89
47
79
93
88
34
87
95
65
71
30
Me
i-Pr
t-Bu
Me
Me
Me
Me
Me
[a]
Conditions: 1 (0.30 mmol), 6 (0.25 mmol), ZrACTHNUGTRNE(UNG t-BuO)4 (0.05 mmol), L3 (0.05 mmol), CH2Cl2 (2 mL), room temperature.
Isolated yield of 7.
Determined by chiral HPLC.
[b]
[c]
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Synthesis of Functionalized Indoles with an a-Stereogenic Ketone Moiety
FULL PAPERS
Figure 2. X-ray structure of compound 3db. Flack parameter
0.01 (2).
bearing substituents respectively at the 7 and 2 posi-
tions, close to the nitrogen atom (entries 7 and 8) re-
Figure 3. Positive NLE observed in the L2-Hf(IV)-n-PrOH-
catalyzed reaction of indole (1a) and 2a.
acted to provide the Friedel–Crafts products with
more moderate enantiomeric excesses. Finally, indole
1g substituted at the nitrogen atom reacted with low
enantioselectivity (entry 9) as we have observed in
other Friedel–Crafts reactions using this catalytic
system.[21,25]
The absolute configuration of compound 3db
(Table 2, entry 10) was determined to be S by X-ray
crystallographic analysis (Figure 2),[26] and for the rest
of the products it was assigned on the assumption of a
uniform reaction mechanism. The stereochemistry of
the products indicates the preference of the indole to
approach the enedione from the re face of the double
bond.
To gain some insight into the mechanistic aspects of
the reaction, we investigated the relationship between
the enantiopurity of ligand L2 and the enantiopurity
of the Friedel–Crafts product 3aa, looking for possible
non-linear effects (NLE). For this purpose, we con-
ducted the reaction using ligand with low ee (0%,
20%, 40%, 60% and 80% ee). As it can be seen in
Figure 3 we found a moderate positive non-linear
effect. These results suggest the presence of various
BINOL-Hf(IV) species of non-monomeric nature
with different thermodynamic stabilities and kinetic
reactivities.[27]
A mechanistic proposal for this reaction is outlined
in Scheme 5. In the first step, the chiral hafnium cata-
lyst, formed from BINOL, HfACHTUNRGTNEUNG(t-BuO)4 and n-PrOH,
Scheme 5. Proposed mechanism for the catalytic cycle of the
Friedel–Crafts alkylation of indoles with (E)-1,4-diaryl-2-
butene-1,4-diones.
might coordinate with the 1,4-diaryl-2-butene-1,4-
dione 2 because of its oxophilicity. Then the indole
would attack the re face of the double bond to give a in the coordination sphere of the Hf atom would have
cationic intermediate 8, which after deprotonation been exchanged for the primary n-propyl alcohols, re-
and exchange of the chiral enolate by alkoxide would leasing the crowding in the environment around the
provide the Friedel–Crafts product and regenerate Hf(IV) ion. In this octahedrical Hf complex[28] the C-
À
the catalyst.
1 C-2 bond of the substrate would prefer an s-trans
To explain the stereochemical outcome of the reac- conformation to avoid the steric repulsion of the rest
tion we propose the TS model shown in Figure 4 of the molecule and one of the ligand naphthyl
which would be formed after coordination of the sub- groups, exposing the re face of the double bond to the
strate to an apical position of the catalytic species. nucleophile, while the si face is shielded by the other
Before this stage, the remaining tert-butoxide groups naphthyl group.
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Gonzalo Blay et al.
FULL PAPERS
Figure 4. Stereochemical models for the Friedel-Crafts reaction.
further purification. Endiones 2 were prepared according
Conclusions
procedures from the literature.[29]
In summary, we have described the first catalytic
enantioselective Friedel-Crafts reaction of indoles
using 1,4-diaryl-2-butene-1,4-diones as electrophiles.
This kind of compound is a challenging substrate on
account of the non-chelating character and reduced
reactivity toward nucleophiles. Besides, the new ste-
Procedure for the Catalytic Enantioselective Friedel–
Crafts Reaction
HfACTHNUTRGNEN(UG t-BuO)4 (21 mL, 0.05 mmol) and n-PrOH (16 mL,
0.2 mmol) were successively added via microsyringe to a so-
lution of L2 (22 mg, 0.05 mmol) in dry dioxane (1 mL)
reogenic center in the resulting dicarbonyl indole de- under nitrogen at room temperature. After 1 h, a solution of
1a (35 mg, 0.30 mmol) and enedione 2a (59 mg, 0.25 mmol)
in dry dioxane (1 mL) was added and the mixture stirred at
room temperature. After 3 h, the reaction mixture was fil-
tered through a short pad of silica gel eluting with diethyl
ether. The solvents were removed under reduced pressure
and the residue chromatographed on silica gel eluting with
hexane/EtOAc (88:12) to give compound 3aa; yield:
81.2 mg (92%). The enantiomeric excess (87%) was deter-
mined by HPLC [Chiralpak AD-H (4.6ꢇ250 mm), hexane:i-
PrOH 85:15, 1 mLminÀ1]: (+)-major tr =35.5 min, (À)-
minor tr =33.3 min; oil; [a]2D5: +305.4 (c 0.8, CHCl3, 87%
ee); 1H NMR (300 MHz, CDCl3): d=8.13 (br s, 1H), 8.06
(dd, J=6.9, 1.5 Hz, 2H), 7.98 (dd, J=7.2, 1.2 Hz, 2H), 7.79
(dd, J=7.8, 1.8 Hz, 1H), 7.55 (tt, J=7.4, 1.5 Hz, 1H), 7.49–
7.34 (m, 6H), 7.25–7.15 (m, 2H), 7.01 (d, J=2.4 Hz, 1H),
5.62 (dd, J=10.2, 3.6 Hz, 1H), 4.26 (dd, J=18.1, 10.2 Hz,
1H), 3.45 (dd, J=18.2, 3.5 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d=199.1 (C), 198.2 (C), 136.5 (C), 136.4 (C), 133.2
(CH), 132.7 (CH), 128.8 (CH), 128.5 (CH), 128.4 (CH),
128.2 (CH), 126.0 (C), 122.8 (CH), 122.5 (CH), 120.0 (CH),
118.7 (CH), 113.2 (C), 111.4 (CH), 42.8 (CH2), 39.6 (CH);
MS (EI): m/z=(%): 353 (M+, 27), 335 (14), 248 (37), 105
(100), 77 (34); HR-MS: m/z=353.1414 (M+), calcd. for
C24H19NO2: 353.1416.
rivative is generated in the a-position to one of the
carbonyl group and therefore this reaction can be
considered as an inversion of the normal reactivity
pattern or umpolung. (E)-4-Oxo-4-arylbutenoates can
also be used as electrophiles. In this case, a stereogen-
ic center is regioselectively formed in an a poisition
to the ester group, with good enantioselectivity. The
success of the reaction is sustained on the use of
chiral Hf(IV) complexes that have been little studied
in asymmetric catalysis.
Experimental Section
General Procedures
Glassware was oven-dried overnight at 1208C. Reactions
were monitored by TLC analysis using Merck Silica Gel 60
F-254 thin layer plates. Flash column chromatography was
1
performed on Merck silica gel 60, 0.040–0.063 mm. H NMR
1
were run at 300 MHz for H and at 75 MHz for 13C NMR in
a Bruker Avance 300 spectrometer, in CDCl3 using residual
non-deuterated solvent (CHCl3) as internal standard (d=
7.26 and 77.0 ppm), unless otherwise stated. Specific optical
rotations were measured in a Perkin–Elmer polarimeter
using sodium light (D line 589 nm). Mass spectra were re-
corded on a Fisons Instruments VG Autospec GC 8000
series. Mass spectra (EI) were run at 70 eV. Mass spectra
(FAB) were carried out at 30 kV in a MNBA matrix. Chiral
HPLC analyses were performed in an Agilent 1100 series in-
strument equipped with a refraction index detector or in a
Hitachi Elite Lachrom instrument equipped with a Hitachi
UV diode-array L-4500 detector, using chiral stationary col-
umns from Daicel. Dioxane was dried over Na-benzophe-
none prior to use. All BINOL-type ligands and all indoles 1
were commercially available and used as purchased without
Acknowledgements
Financial support from the Ministerio de Educaciꢀn y Cien-
cia and FEDER (CTQ 2006-14199) and from Generalitat Va-
lenciana (ACOMP/2009/338) is gratefully acknowledged.
C.V.and A.M. thank the Generalitat Valenciana for grants.
2438
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Adv. Synth. Catal. 2009, 351, 2433 – 2440

Synthesis of Functionalized Indoles with an a-Stereogenic Ketone Moiety
FULL PAPERS
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ꢆ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 2433 – 2440