Intramolecular cooperative C-C bond cleavage reaction of 1,3-dicarbonyl compounds with 2-iodoanilines to give o-(N-Acylamino)aryl ketones and multisubstituted indoles

Article abstract of DOI:10.1002/chem.201500272

A copper-catalyzed C-C bond cleavage reaction of 1,3-dicarbonyl compounds with 2-iodoanilines was developed. In this process, the ortho effect played an important role in the reactivity and a new reaction pathway that involved a (2-aminophenyl)-bis-(1,3-dicarbonyl) copper species was clearly observed by a time-course HRMS analysis of the reaction mixture. Unlike the previous reports, both the nucleophilic and electrophilic parts of the 1,3-dicarbonyl compound were coupled with 2-iodoaniline by C-C bond cleavage to form o-(N-acylamino)aryl ketones, which could be efficiently converted into multisubstituted indoles.

Full text of DOI:10.1002/chem.201500272

DOI: 10.1002/chem.201500272
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Synthetic Methods |Hot Paper|
Intramolecular Cooperative CÀC Bond Cleavage Reaction of
1,3-Dicarbonyl Compounds with 2-Iodoanilines To Give
o-(N-Acylamino)aryl Ketones and Multisubstituted Indoles
Qi Xing,[a, b] Hui Lv,[a] Chungu Xia,[a] and Fuwei Li*[a]
Abstract: A copper-catalyzed CÀC bond cleavage reaction of
1,3-dicarbonyl compounds with 2-iodoanilines was devel-
oped. In this process, the ortho effect played an important
role in the reactivity and a new reaction pathway that in-
volved a (2-aminophenyl)-bis-(1,3-dicarbonyl) copper species
was clearly observed by a time-course HRMS analysis of the
reaction mixture. Unlike the previous reports, both the nu-
cleophilic and electrophilic parts of the 1,3-dicarbonyl com-
pound were coupled with 2-iodoaniline by CÀC bond cleav-
age to form o-(N-acylamino)aryl ketones, which could be ef-
ficiently converted into multisubstituted indoles.
Introduction
In recent years, the development of more efficient and rapid
CÀC bond cleavage methods has attracted much attention be-
cause of its fundamental scientific appeal and potential appli-
cation in organic synthesis.[1] To date, various effective CÀC
bond cleavage strategies have been developed, such as the
use of directing chelating groups,[2] oxidative cleavage,[3] and
the cleavage of functional substrates bearing carbonyl,[4]
ester,[5] carboxyl,[6] cyano,[7] or hydroxyl[8] groups. In particular,
1,3-dicarbonyl compounds have been widely used as versatile
substrates to construct acyl or ketone compounds by CÀC
bond cleavage.[9] The groups of Guo and Koning independent-
ly revealed that a-arylacetic acid esters could be directly ob-
tained by copper-catalyzed coupling of aryl halides and ethyl
acetoacetate and spontaneous deacylation of the coupling
product.[9a,b] Lei and co-workers reported an efficient copper-
catalyzed arylation of ketones by CÀC bond cleavage of 1,3-di-
ones.[9c] As reported in these methods, a functionalized ArX
species acted as an electrophile and reacted with 1,3-dicarbon-
yl compounds to generate a proposed CuIII intermediate,
which underwent CÀC bond cleavage to yield a-aryl ketones
or a-arylacetic acid esters with simultaneous release of one
equivalent of R4COOM (Scheme 1, path a). In other cases, nu-
cleophilic alcohols or amines could also react with a 1,3-dicar-
Scheme 1. Metal-catalyzed CÀC single-bond cleavage.
bonyl compound in the presence of a metallic (e.g., Fe, In)
Lewis acid catalyst to yield the corresponding esters or amides
and one equivalent of the ketone moiety R3COMe[9f–h]
(Scheme 1, path b).
Very recently, we developed an acid-catalyzed acylation reac-
tion of the indole C3ÀH position with 1,3-diones by CÀC bond
cleavage to synthesize 3-acylindoles.[9i] Unfortunately, in all the
cases mentioned above, only acyl or ketone moieties could be
incorporated into the target products after CÀC bond cleav-
age. From the viewpoint of atom economy and synthetic effi-
ciency, developing an efficient CÀC bond cleavage approach
that uses both the reactivity attributes of 1,3-dicarbonyl com-
pounds to construct the target products is of great interest. To
achieve this goal, we speculated that bifunctional substrates
containing both electrophilic and nucleophilic groups might
be a reasonable choice to react with 1,3-dicarbonyl com-
pounds (Scheme 1, path c).
[a] Q. Xing, H. Lv, Prof. Dr. C. Xia, Prof. Dr. F. Li
State Key Laboratory for Oxo Synthesis Oxidation
Lanzhou Institute of Chemical Physics
Chinese Academy of Science
Indoles are a ubiquitous heterocyclic motif in pharmaceuti-
cal agents and natural products.[10] Therefore, the development
of methods to construct these compounds in an efficient
manner is of continuing interest to organic chemists. So far,
many kinds of substrate have been used for indole synthesis;[11]
ortho-haloanilines are one of the most-common substrates and
they react with alkynes or alkenyl halides by Pd-catalyzed
Lanzhou 730000 (P. R. China)
E-mail: fuweili@licp.cas.cn
[b] Q. Xing
Graduate University of Chinese Academy of Sciences
Beijing, 100049 (P. R. China)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201500272.
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domino CÀC and CÀN bond-forming reactions to yield the de-
sired substituted indoles.[12a,b] In addition, the Cu-catalyzed re-
action of 2-iodoaniline with 1,3-diketones in the highly polar
solvent dimethyl sulfoxide (DMSO) could specifically produce
2,3-disubstituted indoles[12c–e] (Scheme 2). In this process, an in-
Table 1. Optimization of the reaction conditions.[a]
Entry[a]
Catalyst
Base
Solvent
Yield [%][b]
3aa
4aa
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
CuI
CuI
CuI
CuI
CuI
–
CuI
CuI
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K3PO4·3H2O
K2CO3
Na2CO3
Cs2CO3
KOtBu
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
hexane
dioxane
CH3CN
DMF
n.d.[c]
trace
34
53
33
n.d.
66
n.d.
75
37
71
74
75
trace
17
8
81 (66)[d]
27[e]
63[f]
76[g]
74[h]
n.d.
n.d.
n.d.
42
59
n.d.
26
n.d.
16
trace
18
20
21
n.d.
12
n.d.
15
15
14
DMSO
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CuI
CuI
Cu2O
CuBr
CuOAc
FeCl2
Co(OAc)2
NiI2
CuI
CuI
CuI
CuI
Scheme 2. Previous synthesis of indoles from 2-iodoanilines and 1,3-dike-
tones, and our work.
Cs2CO3
Cs2CO3
18
11
CuI
termolecular condensation between the nucleophilic amine
and the more-electron-deficient carbonyl group is proposed to
take place first to give imine intermediate A, followed by intra-
molecular C–C cross-coupling to form the indole. Inspired by
this work, we speculated that if we adjust the conditions so
that C–C cross-coupling between the CÀI bond and the meth-
ylene group of the 1,3-dione takes place first, followed by in-
ternal nucleophilic attack of the amino group to one carbonyl
group, after which CÀC bond cleavage would occur. By this
pathway, we would obtain o-(N-acylamino)aryl ketone prod-
ucts. In this process, the amino group and CÀI bond of ortho-
iodoaniline acted as nucleophilic and electrophilic groups, re-
spectively. Its key is to control the selectivity of the CÀC bond-
forming reaction in preference to production of the imine in-
termediate. To our delight, we could tune the reaction solvent
and successfully realize this new reaction pathway to yield o-
(N-acylamino)aryl ketones, which are valuable synthetic inter-
mediates in organic synthesis,[13] for example, in this work, they
can be readily converted to multisubstituted indoles by an
FeCl3-catalyzed reaction. From this perspective, the present
method also provides a facile alternative for indole synthesis.
[a] Reaction conditions: 1a (0.5 mmol, 1 equiv), 2a (1.5 mmol, 3 equiv),
base (1.5 mmol, 3 equiv), metal catalyst (10.0 mol%), solvent (2 mL),
908C, 12 h. [b] Determined by HPLC analysis with acetanilide as an inter-
nal standard. [c] Not detected. [d] 2a (5 equiv) was used, isolated yield in
parentheses. [e] 2a (1 equiv) was used. [f] Cs2CO3 (5 equiv), 2a (5 equiv)
were used. [g] 1108C, 2a (5 equiv) was used. [h] 708C, 2a (5 equiv) was
used.
propan-2-one (3aa) (Table 1, entries 1 and 2). Interestingly,
with the polar solvent acetonitrile, the reaction showed excel-
lent selectivity for 3aa (34% yield) with no concomitant forma-
tion of 2,3-disubstituted indole 4aa (Table 1, entry 3). With the
more-polar solvent DMF, 3aa was obtained in 53% yield, but
4aa was also generated in 42% yield (Table 1, entry 4). In
DMSO 4aa was obtained as the major product in 59% yield
(Table 1, entry 5). All these results indicate that the solvent can
change the reactivity and final-product selectivity of this trans-
formation, probably due to solvent–catalyst interactions.[14]
A
control experiment confirmed that no reaction took place
without the copper catalyst (Table 1, entry 6). After examining
several bases, Cs2CO3 was found to be the most efficient for
this reaction (Table 1, entries 3, 7–10). Compared to CuI
(Table 1, entry 9), Cu2O, CuBr, and CuOAc also efficiently cata-
lyzed this reaction (Table 1, entries 11–13). However, FeCl2,
Co(OAc)2, and NiI2 failed to efficiently catalyze the transforma-
tion (Table 1, entries 14–16). The optimal ratio of 2a/1a was
5:1 (Table 1, entries 17 and 18). Increasing the amount of base
resulted in a decreased product yield (Table 1, entry 19). Con-
ducting the reaction at higher or lower temperatures led to
a slight decrease in the product yield (Table 1, entries 20 and
21).
Results and Discussion
Optimizing the reaction conditions
First, we studied the reaction between 2-iodoaniline (1a) and
acetylacetone (2a). Based on initial speculation that the sol-
vent polarity will affect the reaction selectivity, a series of sol-
vents were examined (Table 1, entries 1–5). Use of non-polar
solvents hexane and dioxane led to no reaction or only trace
amounts of the desired product, o-(N-acylamino)phenyl
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CÀC Bond cleavage
Table 3. Copper-catalyzed reactions of 1a with 1,3-dicarbonyl com-
pounds 2.[a]
With the optimized conditions in hand, we investigated the
substrate scope for this CÀC bond-activation reaction. First,
a wide array of 2-iodoanilines 1 were treated with 2a and
moderate-to-excellent yields of 3 were obtained (Table 2). 2-Io-
doanilines with electron-donating substituents, such as methyl
Entry
2
Product
Yield [%][b]
1
2
3
4
5
6
7
8
9
2a: R3 =H, R1 =R2 =Me
2b: R3 =H, R1 =R2 =Et
2c: R3 =H, R1 =R2 =iPr
2d: R3 =H, R1 =R2 =tBu
2e: R3 =H, R1 =R2 =Ph
2 f: R1 =R2 =R3 =Me
2i: R3 =H, R1 =Ph, R2 =Me
2j: R3 =H, R1 =tBu, R2 =Me
2k: R3 =H, R1 =OtBu, R2 =Me
2l: R3ÀR1 =À(CH2)3À, R2 =Me
3aa
3ab
3ac
3ad
3ae
3af
3ai
3aj
3ak
3al
66
83
68
trace
43
31 (54)[c]
71
82
31
Table 2. Cu-catalyzed reactions of 1 with 2a.[a]
10
68
[a] Reaction conditions: 1a (0.5 mmol),
2 (2.5 mmol), CuI (10 mol%),
Cs2CO3 (1.5 mmol), CH3CN (2 mL), 908C, 12 h. [b] Isolated yield. [c] Yield
obtained at 1108C after 36 h.
3,5-dione (2b) gave the desired 3-acylindoles 3aa and 3ab in
66 and 83% yield, respectively (Table 3, entries 1 and 2). Hin-
dered substrate 2,6-dimethylheptane-3,5-dione (2c) also un-
derwent smooth CÀC bond cleavage to provide 3ac in 68%
yield (Table 3, entry 3). However, the more-hindered substrate
2,2,6,6-tetramethylheptane-3,5-dione (2d) afforded only a trace
of product 3ad (Table 3, entry 4). 1,3-Diphenylpropane-1,3-
dione (2e) also successfully reacted with 1a to give 3ae in
moderate yield (Table 3, entry 5). To our delight, the CÀC bond
cleavage reaction of 3-methylpentane-2,4-dione (2 f), substitut-
ed at the methylene position, proceeded smoothly with an en-
hanced reaction temperature and prolonged reaction time to
give 3af in 54% yield (Table 3, entry 6). Using asymmetric 1,3-
diketone substrates 2i and 2j, 3ai and 3aj were obtained se-
lectively in good yields (Table 3, entries 7 and 8). Tert-butyl-3-
oxobutanoate (2k) also reacted with 1a to produce 3ak in
31% yield (Table 3, entry 9). For cyclic 1,3-diketone 2l, acetyla-
tion product 3al was obtained in 68% yield without observa-
tion of any ring-opening product (Table 3, entry 12).
[a] Reaction conditions: 1 (0.5 mmol), 2a (2.5 mmol), CuI (10.0 mol%),
Cs2CO3 (1.5 mmol), CH3CN (2 mL), 908C, 12 h; isolated yields shown.
and methoxy groups, para to the amino group reacted
smoothly with 2a to provide 3ba and 3ca in 72 and 79%
yield, respectively. 2-Iodo-4-chloroaniline gave 3da in 67%
yield, which offered the possibility for further functionalization.
2-Iodo-4,6-dimethylaniline with methyl groups at both the
ortho- and para positions of the amino group afforded 3 fa in
71% yield. However, the presence of a strong electron-with-
drawing group decreased the efficiency dramatically (e.g.,
3ea). This poor efficiency may due to decreased nucleophilicity
of the amino group. Therefore, the process may be favored by
substrates with electron-donating substituents. To our delight,
2-bromoaniline also reacted smoothly with 2a under the same
conditions, although a relatively lower yield of 3aa (55%) was
obtained compared with the reaction of 1a. (2-Iodophenyl)me-
thanol, with a hydroxyl nucleophile and CÀI electrophile, also
worked efficiently and gave the expected product 2-(2-oxopro-
pyl)benzyl acetate (3ga) in 75% yield. Moreover, this method
could apply to heteroaromatic 2-iodoanilines; for example, re-
action of 4-iodopyridin-3-amine provided N-(4-(2-oxopropyl)-
pyridin-3-yl)acetamide (3ha) in 63% yield.
Intramolecular cyclization
Subsequently, in the presence of a Lewis acid catalyst (FeCl3),
the o-(N-acylamino)aryl ketones 3 underwent efficient cycliza-
tion to produce multisubstituted indoles 5 (Table 4).[13] For ex-
ample, 3aa, 3ab, and more-hindered substrate 3ac afforded
the corresponding 1,2-disubstituted indoles 5a, 5b, and 5c, re-
spectively, in 82–93% yield. o-(N-acylamino)aryl ketone 3af,
with a methyl substituent at the methylene position, also cy-
clized smoothly to form 1,2,3-trisubstituted indole 5d in 78%
yield. o-(N-Acylamino)aryl ketones 3ae and 3ai containing an
acetophenone group underwent cyclization to generate 2-phe-
nylindoles 5e and 5 f in good yields. To our delight, cyclic N-
(2-(2-oxocyclopentyl)phenyl)acetamide (3al) also cyclized suc-
cessfully to produce fused polycyclic 1-(2,3-dihydrocyclopen-
The reactions of 1a with different 1,3-dicarbonyl compounds
2 were also investigated (Table 3). Diketone 2a and heptane-
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Table 4. Fe-catalyzed synthesis of 1,2-disubstituted indoles 5 from 3.[a]
Scheme 3. Control reactions of 2a with 4-iodoaniline, iodobenzene, and ani-
line. Ac=acetyl.
products. For this reaction in acetonitrile a completely different
product, namely an o-(N-acylamino)aryl ketone, was isolated as
the major product, along with a small quantity of an indole by-
product. We envisioned that a different reaction pathway leads
to the different reaction outcome. One possible route for the
indole byproduct formation is further annulation of the o-(N-
acylamino)aryl ketone 3 through intramolecular condensation.
o-(N-Acylamino)aryl ketone 3aa could be transformed, albeit in
low yield (21%), into 2,3-substituted indole 4aa in the pres-
ence of CuI and base in DMSO at 908C (Scheme 4a). Other-
[a] Reaction conditions: 3 (0.25 mmol), FeCl3 (10 mol%), CH3CN (1 mL),
908C, 12 h; isolated yields shown.
taindol-4(1H)-yl)ethanone (5g) in 87% yield. Moreover, o-(N-
acylamino)aryl ketones with methyl- and chlorine substituents
on the phenyl subunit (3ba and 3da) provided the corre-
sponding cyclized products 5h and 5i in 91 and 89% yield, re-
spectively. This reaction provides a practical application for this
cascade reaction.
Mechanistic study
A set of control reactions were conducted to gain some insight
into the reaction mechanism. Unlike 1a, the reaction of 4-io-
doaniline with 2a produced 1-(4-aminophenyl)propan-2-one
and 3-(4-aminophenyl)pentane-2,4-dione in 21 and 19% yield,
respectively, along with a trace amount of N-(4-iodophenyl)a-
cetamide, but no N-(4-(2-oxopropyl)phenyl)acetamide was de-
tected (Scheme 3a). Furthermore, when aniline reacted with
2a, only 16% yield of N-phenylacetamide was obtained
(Scheme 3b). After the reaction of iodobenzene with 2a, 1-
phenylpropan-2-one and 3-phenylpentane-2,4-dione were ob-
tained in 21 and 17% yield, respectively (Scheme 3c). More-
over, when a mixture of aniline and iodobenzene reacted with
2a, N-phenylacetamide (22%), 1-phenylpropan-2-one (18%),
and 3-phenylpentane-2,4-dione (13%) were obtained
(Scheme 3d). Clearly, the internal ortho effect between the CÀI
bond and the amino group plays a decisive role in the reaction
activity and selectivity, therefore with 4-iodoaniline as the sub-
strate only intermolecular acylation of amine group or alkyla-
tion of CÀI bond occurred while no N-(4-(2-oxopropyl)pheny-
l)acetamide was obtained. Moreover, the reactivity of all these
control substrates was much lower than that of 1a.
Scheme 4. Control reactions for the synthesis of 4aa.
wise, imine A could also be generated in situ by condensation
of 1a and 2a, then provide indole 4aa in excellent yield (87%)
under the same conditions (Scheme 4b). We conclude that in
DMSO the condensation of the amino group of 1a with 1,3-di-
ketone 2a occurs first, followed by intramolecular C–C cross-
coupling of A to afford 2,3-disubstituted indole 4aa. On the
contrary, for our procedure in acetonitrile[15] CÀI bond activa-
tion may be the first step, followed by intramolecular attack of
the amino group to one carbonyl group, which results in the
formation of o-(N-acylamino)aryl ketones 3.
In-situ HRMS (ESI) analysis of the reaction mixture was per-
formed at different time points. At t=0, the peak correspond-
ing to 1a (m/z 219.9627) was detected (Figure 1). With pro-
longed reaction time, a peak at m/z 376.06 appeared and in-
creased gradually for the first 3 h, then decreased until it had
almost disappeared by 16 h. In the meantime, the peak corre-
In early reports, the reactions of 1a and 1,3-diketones in
DMSO mainly afford 2,3-disubstituted indoles as the major
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sponding to 1a decreased while that of 3aa (m/z 214.08) rose
gradually. Therefore, we speculated that III (m/z 376.06
[III+Na]+; Scheme 5, Figure 2) might be an intermediate in this
CÀC bond cleavage transformation, which further supported
CÀI bond activation as the first step of this reaction.
Scheme 5. Plausible mechanistic pathway for the reaction of 1 and 2.
Figure 2. Calculated HRMS spectrum for intermediate III.
Based on the results of the above-mentioned control reac-
tions and HRMS investigation, a proposed mechanism for this
CÀC bond cleavage reaction is shown in Scheme 5. First, with
the assistance of base, copper reacts with 2a to produce cop-
per(I) complex I, which undergoes further oxidative addition
with 1a to give copper(III) intermediate II. Intermediate III is
the generated by ligand exchange between iodine and
a second molecule of 2a. Subsequently, intramolecular nucleo-
philic attack of the amino group onto one carbonyl group of
intermediate III is accompanied by CÀC bond cleavage to give
intermediate IV. Intermediate IV undergoes reductive elimina-
tion to furnish intermediate V. The subsequent reaction of 2a
and V regenerates the copper(I) intermediate I for the next cat-
alytic cycle.
Conclusion
We have developed an efficient method to synthesize (N-acyla-
mino)aryl ketones by copper-catalyzed CÀC bond cleavage be-
tween 2-iodoanilines and 1,3-dicarbonyl compounds. In this
process, both the nucleophilic and electrophilic parts of the
1,3-dicarbonyl compounds were coupled with 2-iodoanilines to
Figure 1. Observed HRMS data for intermediate III and product 3aa at dif-
ferent time points.
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[4] For selected examples of CÀC bond cleavage reactions of substrates
with carbonyl groups, see: a) C. Zhang, Z. Xu, T. Shen, G. Wu, L. Zhang,
N. Jiao, Org. Lett. 2012, 14, 2362–2365; b) Q. Gao, Y. Zhu, M. Lian, M.
Liu, J. Yuan, G. Yin, A. Wu, J. Org. Chem. 2012, 77, 9865–9870.
[5] For selected examples of CÀC bond cleavage reactions of substrates
with an ester group, see: a) Y. Chen, Y. Wang, Z. Sun, D. Ma, Org. Lett.
2008, 10, 625–628; b) R. Shang, Y. Fu, J.-B. Li, S.-L. Zhang, Q.-X. Guo, L.
Liu, J. Am. Chem. Soc. 2009, 131, 5738–5739.
[6] For selected examples of CÀC bond cleavage reactions of substrates
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Chem. Int. Ed. 2012, 51, 227–231; Angew. Chem. 2012, 124, 231–235;
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[7] For selected examples of CÀC bond cleavage reactions of substrates
with a cyano group, see: a) C. Nꢁjera, J. M. Sansano, Angew. Chem. Int.
Ed. 2009, 48, 2452–2456; Angew. Chem. 2009, 121, 2488–2492; b) Y.
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form o-(N-acylamino)aryl ketones, which could be efficiently
converted into multisubstituted indoles by an FeCl3-catalyzed
reaction. The reaction solvent played a decisive role in selec-
tion of the reaction pathway. Furthermore, an ortho effect be-
tween the CÀI and amine functionalities showed significant in-
fluence on the coupling with the entire 1,3-dicarbonyl com-
pound and improved the reactivity of the transformation. This
simple and practical method complements the classical
method for the construction of o-(N-acylamino)aryl ketones
and indoles, and has a practical value to synthetic chemists de-
signing new transformations by CÀC bond cleavage.
Experimental Section
Reaction of 1a and 1,3-dicarbonyl compounds 2
[8] For selected examples of CÀC bond cleavage reactions of substrates
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2010, 122, 4557–4560.
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Compound 1a (0.5 mmol), 1,3-dicarbonyl compound 2 (2.5 mmol),
CuI (0.05 mmol), Cs2CO3 (1.5 mmol), and CH3CN (2 mL) were added
to a Schlenk tube, which was then capped. The mixture was stirred
for 12 h at 908C. After cooling to room temperature, the resultant
reaction mixture was purified by flash column chromatography on
silica gel.
Acknowledgements
This work was supported by the Chinese Academy of Sciences
and the National Natural Science Foundation of China
(21133011 and 21373246).
Keywords: CÀC bond cleavage · copper · domino reactions ·
ortho effect · reaction mechanisms
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Received: January 21, 2015
Published online on && &&, 0000
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Chem. Eur. J. 2015, 21, 1 – 7
www.chemeurj.org
6
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÝÝ These are not the final page numbers!

Full Paper
FULL PAPER
&
Synthetic Methods
Q. Xing, H. Lv, C. Xia, F. Li*
&& – &&
Intramolecular Cooperative CÀC Bond
Cleavage Reaction of 1,3-Dicarbonyl
Compounds with 2-Iodoanilines To
Give o-(N-Acylamino)aryl Ketones and
Multisubstituted Indoles
Break it up! An intramolecular coopera-
tive CÀC bond cleavage reaction be-
tween 2-iodoanilines and 1,3-dicarbonyl
compounds was developed to provide
efficient access to o-(N-acylamino)aryl
ketones, which could further be con-
verted to multisubstituted indoles (see
scheme).
Chem. Eur. J. 2015, 21, 1 – 7
www.chemeurj.org
7
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
&
&
These are not the final page numbers! ÞÞ