Rhodium(III)-Catalyzed Tandem [2+2+2] Annulation–Lactamization of Anilides with Two Alkynoates via Cleavage of Two Adjacent C?H or C?H/C?O bonds

Article abstract of DOI:10.1002/asia.201600943

An electron-deficient Cp^E rhodium(III) complex bearing a cyclopentadienyl ligand with two ethyl ester substituents catalyzes the tandem [2+2+2] annulation–lactamization of acetanilides with two alkynoates via cleavage of adjacent two C?H bonds to give densely substituted benzo[cd]indolones. The reactions of meta-methoxy-substituted acetanilides with two alkynoates also provided benzo[cd]indolones via cleavage of adjacent C?H/C?O bonds. Furthermore, 3,5-dimethoxyacetanilides reacted with two alkynoates to give dearomatized spiro compounds.

Full text of DOI:10.1002/asia.201600943

CHEMISTRY
AN ASIAN JOURNAL
www.chemasianj.org
Accepted Article
Title: Rhodium(III)-Catalyzed Tandem [2+2+2] Annulation-Lactamization of Anilides
with Two Alkynoates via Cleavage of Adjacent Two C-H or C-H/C-O bonds
Authors: Miho Fukui; Yu Shibata; Yuki Hoshino; Haruki Sugiyama; Kota Teraoka;
Hidehiro Uekusa; Keiichi Noguchi; Ken Tanaka
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To be cited as: Chem. Asian J. 10.1002/asia.201600943
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Chemistry - An Asian Journal
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COMMUNICATION
Rhodium(III)-Catalyzed Tandem [2+2+2] Annulation-Lactamization
of Anilides with Two Alkynoates via Cleavage of Adjacent Two C–
H or C–H/C–O bonds
Miho Fukui,[a,b] Yu Shibata,*[a] Yuki Hoshino,[b] Haruki Sugiyama,[c] Kota Teraoka,[c] Hidehiro Uekusa,[c]
Keiichi Noguchi,[d] and Ken Tanaka*[a,b]
Abstract: It has been established that an electron-deficient CpE-
rhodium(III) complex catalyzes the tandem [2+2+2] annulation-
lactamization of acetanilides with two alkynoates via cleavage of
adjacent two C–H bonds to give densely substituted
banzo[cd]indolones. The reactions of meta-methoxy-substituted
acetanilides with two alkynoates also provided benzo[cd]indolones
via cleavage of adjacent C–H/C–O bonds. Furthermore, 3,5-
dimethoxyacetanilides reacted with two alkynoates to give
dearomatized spiro compounds.
temperature under air to give densely substituted
banzo[cd]indolones[7] (bottom, Scheme 1). Surprisingly, the
reactions of meta-methoxy-substituted acetanilides with two
alkynoates also provided benzo[cd]indolones via unprecedented
adjacent C–H/C–O bond cleavage (bottom, Scheme 1).[8]
Previous work
H
R
Rh(III) catalyst
R
N
[3+2] annulation
H
R
R
Ac
H
+
R
H
R
R
N
Transition-metal-catalyzed oxidative annulations of aromatic
compounds with alkynes via directed C–H bond cleavage are
atom- and step-economical methods for the synthesis of
carbocycles and heterocycles.[1] For example, the rhodium(III)-
catalyzed oxidative [3+2] annulation of acetanilides with alkynes
affords substituted indoles through cleavages of C–H and N–H
bonds (top, Scheme 1).[2] Alternatively, the palladium(II)-
catalyzed oxidative [2+2+2] annulation of acetanilides with two
molecules of diarylacetylenes affords densely substituted
aminonaphthalenes through cleavages of adjacent two C–H
Ac
Pd(II) catalyst
R
H
[2+2+2] annulation
N
(R = aryl)
Ac
This work
O
OR3
R2
H
(OMe)
H
R2
cat.
R2
[CpERhCl2
] (1)
2
R1
+
cat. Ag(I)/Cu(II)
room tem perature
under air
R1
NH
Ac
O
O
OR3
N
Ac
[2+2+2] annulation-lactam ization
bonds (middle, Scheme 1).[3] However, there are
a few
CO2Et
Me
Me
examples of the oxidative [2+2+2] annulation employing a protic
directing group due to difficulty of selective cleavage of adjacent
two C–H bonds without cleavage of the hetero–H bond.[4] On the
other hand, we have recently reported that the oxidative [3+2]
annulation of acetanilides with alkynes proceeds at room
temperature under air in the presence of catalytic amounts of
electron-deficient rhodium(III) complex [CpERhCl2]2 (1), AgSbF6,
and Cu(OAc)2.[5,6] In this paper, we have established that an
electron-deficient CpE-rhodium(III) complex catalyzes the
tandem [2+2+2] annulation-lactamization of acetanilides with two
alkynoates via cleavage of adjacent two C–H bonds at room
Cl
Rh
Cl
Me
EtO2
C
2
[CpERhCl2
] (1)
2
Scheme 1. Oxidative annulations of acetanilides with alkynes.
In the course of our study of the oxidative [3+2] annulation of
acetanilides with alkynes using 1 as a precatalyst,[5], we found
that the reaction of 4’-methoxyacetanilide (2a) and ethyl 2-
butynoate (3a) in acetone afforded not indole 4aa but
benzo[cd]indolone 5aa as a major product (Table 1, entry 1).
The use of CH2Cl2 as a solvent accelerated the reaction, but led
to a complex mixture of products. Fortunately, the use of
CH2Cl2/acetone (1:1) balanced the product yield and reaction
rate (entry 2). The use of 3 equiv of 3a further improved the yield
of 5aa (entry 3). Screening the amount of Cu(OAc)2 (entries 3–6)
revealed that 20 mol % was optimum (entry 5). With respect to
silver salts, the use of AgNTf2 slightly improved the yield of 5aa
(entry 7). To judge the best silver salt, the reactions of 4’-
bromocetanilide (2b) were tested using AgSbF6 and AgNTf2
(entries 8 and 9). The use of AgNTf2 afforded 5ba in significantly
higher yield than that of AgSbF6 (entry 9). Under optimized
conditions, the use of [Cp*RhCl2]2 instead of 1 did not afford 5aa
(entry 10).[9] Importantly, product distribution highly depends on
the terminal substitutents on the alkynoates. The reactions of
secondary- or tertiary-alkyl substituted ones 3b–d with 2a
afforded not benzo[cd]indolones 5 but regioisomeric indoles 4’
as major products (entries 11–13). Furthermore, phenyl-
substituted one 3e reacted with 2a to give indole 4ae (entry
14).[10]
[a]
[b]
M. Fukui, Dr. Y. Shibata, Prof. Dr. K. Tanaka
Department of Chemical Science and Engineering, Tokyo Institute
of Technology, O-okayama, Meguro-ku, Tokyo 152-8550, Japan
E-mail: ktanaka@apc.titech.ac.jp
E-mail: yshibata@apc.titech.ac.jp
http://www.tuat.ac.jp/~tanaka-k/
M. Fukui, Y. Hoshino, Prof. Dr. K. Tanaka
Department of Applied Chemistry, Graduate School of Engineering,
Tokyo University of Agriculture and Technology, Koganei, Tokyo
184-8588, Japan
[c]
[d]
H. Sugiyama, K. Teraoka, Prof. Dr. H. Uekusa
Department of Chemistry, Tokyo Institute of Technology, O-
okayama, Meguro-ku, Tokyo 152-8550, Japan
Prof. Dr. K. Noguchi
Instrumentation Analysis Center, Tokyo University of Agriculture and
Technology, Koganei, Tokyo 184-8588, Japan
Supporting information for this article is given via a link at the end of
the document.
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COMMUNICATION
CO2R3
10 mol %
40 mol % AgNTf2
1
R2
R2
R2
Table 1. Optimization of reaction conditions[a]
R1
20 mol % Cu(OAc)2¥H2
O
H
+
N
R1
O
CH2Cl2/acetone (1:1)
RT, 72 h
CO2R3
Ac
N
under air
10 mol %
40 mol % AgX
1
Ac
2
3 (3 equiv)
5
R1
R2
0Ğ80 mol % Cu(OAc)2¥H2
O
CO2Et
CO2Me
CO2iPr
H
+
N
CH2Cl2/acetone (1:1), RT, 72 h
under air
Me
Me
Me
MeO
Me
Me
MeO
Me
CO2R3
Ac
MeO
2a (R1 = OMe)
2b (R1 = Br)
(3 equiv)
Me
Me
O
O
O
3a (R2 = Me, R3 = Et)
3b (R2 iPr, R3 = Et)
3c (R2 = Cy, R3 = Me)
Me
Cl
N
N
N
=
Rh
Me Cl
Me
Ac
Ac
Ac
5aa / 61% (54% [a]
)
5af / 61%
CO2Et
5ag / 60% (57% [a]
)
3d (R2
=
tBu, R3 = Me)
2
3e (R2 = Ph, R3 = Et)
[Cp*RhCl2
]
2
CO2tBu
CO2Me
CO2R3
R2
Me
MeO
Me
nBu
nBu
Ph(CH2
MeO
)
(CH2
O
)3Ph
3
CO2R3
R2
R2
R1
R1
MeO
+
+
R1
R2
CO2R3
O
O
O
N
N
N
N
N
N
Ac
Ac
Ac
5ah / 29%
Ac
Ac
5aj / 58%
CO2Et
5ai / 54% (42% [a]
)
Ac
4
4'
5
CO2Me
CO2Me
Yield [%][b]
[Cu]
[mol %]
Cl(CH2
MeO
)
(CH2
)
3Cl
R
R
3
Entry
2
3 (equiv)
AgX
MeO
MeO
OMe
O
4
4’
5
Br
1[c]
2
2a 3a (2.2)
2a 3a (2.2)
2a 3a (3.0)
2a 3a (3.0)
2a 3a (3.0)
80
80
80
40
20
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
7
9
8
8
9
<1
<1
<1
<1
<1
39
53
65
63
69
O
O
N
N
N
Ac
Ac
Ac
5ba / 49% (R = Me)
5bi / 35% (R nBu)
CO2Et
Me
5ak / 56%
5al / 32% (45% conv of 2a)
3
=
4
CO2Et
Me
CO2Et
Me
Me
R
R
5
F
Me
6
2a 3a (3.0)
2a 3a (3.0)
2b 3a (3.0)
2b 3a (3.0)
2a 3a (3.0)
2a 3b (3.0)
2a 3c (3.0)
2a 3d (3.0)
2a 3e (3.0)
0
AgSbF6
AgNTf2
AgSbF6
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
AgNTf2
6
<1
<1
<1
<1
0
77[e]
42[e]
60[e]
<1
42
71
29
49
0
O
O
O
N
N
N
7
20
20
20
20
20
20
20
20
8
Ac
5ca / 57%
Ac
Ac
8
5
5da / 65% (R = Me)
5di / 45% (R = nBu)
5ea / 36% (49% conv of 2e)
9
5
CO2Et
Me
CO2Et
CO2Et
10[d]
11
12
13
14
0
Me
Me
Me
Me
Me
11
<5
31[e]
81[e]
<5
<5
0
CO2Et
O
O
N
N
F3
C
Me
NHAc
Ac
Ac
Me
6ha / 52%[b]
5fa / 11% (22% conv of 2f)
5ga / 58%
<5
CO2Et
CO2Et
Me
Me
Me
Me
[a] 1 (0.010 mmol), AgX (0.040 mmol), Cu(OAc)2•H2O (0–0.080 mmol), 2
(0.100 mmol), 3 (0.220–0.300 mmol), CH2Cl2 (0.5 mL), and acetone (0.5 mL)
were used. [b] Determined by 1H NMR. [c] Acetone (1.0 mL) was used as a
solvent. [d] [Cp*RhCl2]2 was used instead of 1. [e] Isolated yield.
O
O
N
N
R
H
Me
7ha / 50% [c]
5ia (R = Boc) / 0%
[7ia (R = H) / 38% ]
The scope of the rhodium(III)-catalyzed tandem oxidative
[2+2+2] annulation-lactamization of anilides 2 with alkynoates 3
is shown in Scheme 2. With respect to alkynoates, not only ethyl
2-butynoate (3a) but also various primary alkyl-substituted
propiolates (3f–l) could participate in this reaction, while the use
of methoxymethyl substituted one 3l resulted in low conversion
presumably due to its high coordination ability to rhodium. The
loading of 1 could be reduced to 5 mol % with slight erosion of
the product yields (5aa, 5ag, and 5ai). With respect to
acetanilides, not only 4’-methoxyacetanilide (2a) but also para-
or meta-substituted and nonsubstituted ones 2b–g could
participate in this reaction, while electron-poor acetanilides 2e,f
showed low reactivity. When using ortho-substituted acetanilide
2h, not the corresponding benzo[cd]indolone but aminoester
6ha was generated. Fortunately, treatment with KOH in EtOH
furnished the corresponding N–H lactam 7ha. With respect to
the directing group, N-Boc-protected aniline 2i reacted with 3a to
give not protected lactam 5ia but N–H lactam 7ia in low yield.
Scheme 2. Oxidative [2+2+2] annulation via cleavage of two C–H bonds. 1
(0.010 mmol), AgNTf2 (0.040 mmol), Cu(OAc)2•H2O (0.020 mmol), 2 (0.100
mmol), 3 (0.300 mmol), CH2Cl2 (0.5 mL), and acetone (0.5 mL) were used.
The cited yields are of the isolated products. [a] 1 (0.0050 mmol), AgNTf2
(0.020 mmol), and Cu(OAc)2•H2O (0.010 mmol) were used. [b] 1H NMR yield.
[c] After concentration of the reaction mixture, the residue was treated with
KOH (0.500 mmol) in EtOH at RT for 2 h.
Surprisingly, the reaction of meta-methoxyacetanilide (2j) with
3a afforded a mixture of benzo[cd]indolones 5ja and 5ca via
cleavage of adjacent two C–H and C–H/C–O bonds,
respectively (Scheme 3, entry 1).[8] Similarly, meta-
acetoxyacetanilide (2k) also reacted with 3a to give
benzo[cd]indolones 5ka and 5aa (entry 2). The reaction of 2’,3’-
ethylenedioxyacetanilide (2l) with 3a afforded ether 5la and
alcohol 8. The formation of 8 confirms the elimination of the
alcohol in this C–O bond cleavage reaction (entry 3). Gratifyingly,
the reaction of 5’-trifluoromethyl-3’-methoxyacetanilide (2m) with
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10.1002/asia.201600943
COMMUNICATION
prepared by the rhodium(III)-catalyzed ortho-C–H olefination[6b]
followed by hydrogenation, was also capable of reacting with 3a
to give N–H lactam 7pa (entry 14).
Entry
2
3
Product / Isolated Yield
CO2Et
Me
CO2Et
Me
Me
Me
Me
These facile C–O bond cleavage reactions prompted us to
investigate the reaction of 3,5-dimethoxyacetanilide (2q). As
shown in Scheme 4, the reaction of 2q with 3a proceeded
sluggishly to give not the corresponding benzo[cd]indolone but
dearomatized spiro compound 9qa in low yield[11] along with a
small amount of its rhodium(I) complex 10. We estimated that
regeneration of a rhodium(III) complex from 10 by oxidation is
slow. Indeed, increasing the amount of the copper(II) oxidant to
100 mol % and decomplexation of 10 by quenching with iron(III)
chloride increased the yield of 9qa to 53%. In order to prove the
presence of 10 in the catalytic cycle, the reaction of 2q with 3a
was conducted using 10 as a catalyst. Indeed, 9qa was obtained
in reasonable yield (See Supporting information). A series of
alkynoates 3f,g and 3i–k could participate in the reactions with
2q to give the corresponding spiro products.
H
+
RO
N
O
O
Ac
CO2Et
N
N
RO
Ac
Ac
1
2
2j (R = Me)
2k (R = Ac)
3a
3a
5ja / 33%
5ka / 38%
5ca / 28%
5ca / 23%
CO2Et
Me
CO2Et
Me
Me
Me
Me
O
O
O
O
O
H
+
N
O
O
CO2Et
Ac
N
N
HO
Ac
5la / 32%
Ac
3
2l
3a
8 / 28%
CO2R3
R2
OMe
R2
R2
H
O
F3
C
N
CO2R3
N
F3
C
Ac
Ac
4
5
6
7
2m
2m
2m
2m
3a (R
=
Me, R' = Et)
5fa / 53%
5m f / 51%
3f (R2
=
Me, R3
Me, R3
=
Me)
10 mol %
40 mol % AgNTf2
1
3g (R2
=
=
iPr)
5m g / 65%
5m i / 26%
OMe
R1
3i (R
= nBu, R' = Et)
100 mol % Cu(OAc)2¥H2
O
+
CO2Et
H
CH2Cl2/acetone (1:1), RT, 48 h, under air
then
OMe
R2
R2
MeO
N
CO2R2
Me
Ac
FeCl3 (2 equiv), RT, 16 h
2q
3
H
CpE
Rh
O
Me
N
CO2Et
CO2R2
R1
N
Me
Ac
CO2Et
Me
Ac
MeO
O
MeO
O
R1
8
2n
3a
5ga / 12%
Me
CO2R3
CO2R2
NHAc
CO2Et
NHAc
OMe
R2
R2
R2
9
10
H
O
N
CO2Et
Me
CO2R3
Me
Me
CO2Me
CO2iPr
Me
N
Me Ac
MeO
O
MeO
O
MeO
H
Me
Me
Me
9[a]
2o
2o
2o
2o
2o
3a (R2 = Me, R3
=
Et)
Me)
iPr)
Et)
7ha / 73%
7of / 49%
7og / 33%
7oi / 49%
7oj / 51%
CO2Et
NHAc
CO2Me
NHAc
CO2iPr
NHAc
10[a]
11[a]
12[a]
13[a]
3f (R2
3g (R2
3i (R2
=
Me, R3
Me, R3
nBu, R3
=
O
=
=
9qa / 13% (10 / 4% )[a]
9qa / 53% (10 / 0% )
9qf / 30%
9qg / 24%
=
=
3j [R2
=
(CH2
)
3Ph, R3
=
Me]
CO2Et
CO2Et
CO2Me
CO2Me
nBu
MeO
Ph(CH2
)
Cl(CH2)
3
3
OMe
MeO
MeO
Me
Me
Me
nBu
(CH2
CO2Me
)
3Ph
(CH2
CO2Me
)3Cl
H
CO2Et
NHAc
O
O
O
O
N
NHAc
NHAc
CO2Et
N
n-C8H17 Ac
H
n-C8H17
9qi / 30%
9qj / 44%
9qk / 55%
14[a]
2p
3a
7pa / 55%
Scheme 4. Dearomative [2+2+1] annulation. 1 (0.010 mmol), AgNTf2 (0.040
mmol), Cu(OAc)2•H2O (0.100 mmol), 2q (0.100 mmol), 3 (0.300 mmol), FeCl3
(0.200 mmol), CH2Cl2 (0.5 mL), and acetone (0.5 mL) were used. The cited
yields are of the isolated products. [a] A reaction was conducted using
Cu(OAc)2•H2O (0.020 mmol) for 72 h without quenching with FeCl3.
Scheme 3. Oxidative [2+2+2] annulation via cleavage of C–H/C–O bonds.
Reactions were conducted using 1 (0.010 mmol), AgNTf2 (0.040 mmol),
Cu(OAc)2•H2O (0.020 mmol), 2 (0.100 mmol), 3 (0.300 mmol), CH2Cl2 (0.5
mL), and acetone (0.5 mL) at RT under air for 72 h. [a] After concentration of
the reaction mixture, the residue was treated with KOH (0.500 mmol) in EtOH
at RT for 2 h.
Plausible mechanisms for the formation of 4, 5, and 9 from 2
and 3a are shown in Scheme 5. First, C–H bond cleavage of 2
3a proceeded smoothly to give benzo[cd]indolone 5fa in
significantly higher yield than that of 2f with 3a (entry 4). The
reactions of 2m with various alkynoates also proceeded to give
the corresponding benzo[cd]indolones (entries 5–7). On the
contrary, the reaction of 5’-methyl-3’-methoxyacetanilide (2n)
with 3a was sluggish (entry 8). Fortunately, the reaction of
sterically hindered regioisomer 2o with 3a afforded N–H lactam
7ha after treatment with KOH in significantly higher yield than
that of 2h with 3a (entry 9). A series of alkynoates could also
participate in the reactions with 2o (entries 10–13). In addition,
more sterically hindered 2’-octyl-5’-methoxyacetanilide (2p),
by rhodium(III) species
A affords rhodacycle B. Next,
regioselective insertion of 3a into B gives rhodacycle C.
Deprotonation and reductive elimination furnishes 4 and a
rhodium(I) species. On the other hand, insertion of 3a into C
gives dienylrhodium D. Electrophilic metalation of the electron-
rich anilide ring produces spiro rhodacycle E. Nucleophilic attack
of the dienylrhodium moiety to the electrophilic 3-position of the
anilide ring and lactamization gives intermediate F.[12] When R1 =
H, deprotonation from intermediate
F affords 5 and the
rhodium(I) species. On the other hand, when R1 = OMe, β-
alkoxy elimination[13] from intermediate F affords 5 and the
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COMMUNICATION
CpE
MeO
Me
CpE
Rh
CO2Et
Me
Rh
CpE
R1
R1
AcO
H
Rh
A
CO2Et
O
O
NHAc
Me
–AcOH
R2
N
H
2
Me
R2
N
Me
CpERh(I), H+
E'
(R1 = H)
H
CO2Et
Me
CO2Et
Me
B
or
CpE
Me
CpERh(III)+, OMe
(R1 = OMe)
Me
R1
Me
Me
CO2Et
R1
CO2Et
Me
Rh
Me
Rh CpE
3a
–EtOH
O
O
R2
CO2Et
R2
R2
EtO2
C
N
N
R1
CO2Et
Me
Me
NHAc
R1
CO2Et
Ac
Ac
CpE
CO2Et
3a
E
F
5
Rh
O
R2
Me
R2
H2
O
N
Rh
R1 = R2 = OMe
N
CpE
ĞMeOH, ĞH+
Ac
H
H
Me
CpE
C
D
Me
CO2Et
CpE
Me
Rh
CO2Et
ĞCpERh(I)
ĞH+
CO2Et
Me
Me
MeO
[O]
MeO
Rh
MeO
Me
Me
ĞCpERh(III)2+
R1
CO2Et
NHAc
CO2Et
NHAc
O
CO2Et
O
CO2Et
NHAc
O
Me
N
G
10
9qa
R2
Ac
4
Scheme 5. Plausible mechanisms for formation of 4, 5, and 9.
catalytically active rhodium(III) species. However, the copper(II)
co-catalyst was necessary in order to reoxidize rhodium(I)
species generated through the competing oxidative [3+2]
annulation. The observed regioselective formation of 4 and 5
can be explained by the regioselective insertion of 3a into B as a
result of steric repulsion between the CpE ligand and
ethoxycarbonyl group, which is bulkier than the methyl group.[14]
Indeed, as shown in Table 1, the reactions of secondary- or
tertiary-alkyl substituted alkynoates 3b–d with 2a afforded not
indoles 4 and benzo[cd]indolones 5 but regioisomeric indoles 4’
as major products presumably due to steric repulsion between
the CpE ligand and bulky secondary- and tertiary-alkyl groups.
Furthermore, steric hindrance of alkynoates 3b–e might deter
their double insertion into rhodacycle B, which accounts for the
preferential formation of 4 and 4’ over 5. When R1 = R2 = OMe
(2q), the nucleophilic attack of the dienylrhodium moiety to the
cationic anilide ring, stabilized with two meta-methoxy groups of
E, would be slow. Instead, hydration of the methoxy group (R2)
of E leading to intermediate G followed by reductive elimination
proceeds to generate rhodium(I)-diene complex 10. Oxidation of
10 affords 9qa and regenerates the rhodium(III) species.
Similarly, when R1 = OMe and R2 = Me (2n), the conversion of E
to F would be slow due to stabilization of the cationic anilide ring
with the meta-methoxy and methyl groups. In this case,
hydration of the methoxy group (R1) of E would not proceed due
to the steric hindrance around the rhodium center. On the
contrary, in spiro rhodacycle E’ derived from 2o and 3a, the
meta-methoxy group compensates the decreasing resonance
stabilization of the cationic anilide ring with the acetylamino
group as a result of steric repulsion between the acetylamino
and ortho-methyl groups (green). Therefore, 2o showed higher
reactivity than 2n.
stoichiometric amount of the rhodium(III) complex was
conducted (Scheme 6). Indeed, η5-dihydrobenzo[cd]indolone
rhodium(III) complex 11 (R1 = R2 = Me in F) was isolated in 43%
yield.
Ğ
CO2Me
NTf2
1 (0.5 equiv)
AgNTf2 (2 equiv)
Cu(OAc)2¥H2
Me
Me
Rh+ CpE
Me
Me
Me
O (1 equiv)
+
H
CH2Cl2/acetone (1:1), RT, 1 h
under Ar
O
Me
N
CO2Me
N
Me
Ac
Ac
11 / 43%
2r
3f
(3 equiv)
Scheme 6. Isolation of a rhodium(III)/η5-dihydrobenzo[cd]indolone complex.
In summary, we have established that an electron-deficient
CpE-rhodium(III) complex catalyzes the tandem [2+2+2]
annulation-lactamization of acetanilides with two alkynoates via
cleavage of adjacent two C–H bonds to give densely substituted
banzo[cd]indolones. The reactions of meta-methoxy-substituted
acetanilides
with
two
alkynoates
also
provided
benzo[cd]indolones via cleavage of adjacent C–H/C–O bonds.
Furthermore, 3,5-dimethoxyacetanilides reacted with two
alkynoates to give dearomatized spiro compounds.
Acknowledgements
This work was supported partly by ACT-C from JST (Japan),
Grants-in-Aid for Scientific Research (Nos. 26102004 and
25105714) from MEXT (Japan), and a Grant-in-Aid for Research
Activity Start-up (No. 15H06201) from JSPS (Japan). We are
grateful to Umicore for generous support in supplying the
rhodium complex.
In order to confirm intermediacy of F, the reaction of 3,5-
dimethylacetanilide (2r) with 3f in the presence of
a
For internal use, please do not delete. Submitted_Manuscript

Chemistry - An Asian Journal
10.1002/asia.201600943
COMMUNICATION
2016, 52, 1681; b) K. Nakamura, M. Tobisu, N. Chatani, Org. Lett. 2015,
17, 6142; c) Y. Zhao, V. Snieckus, Org. Lett. 2015, 17, 4674; d) M.
Tobisu, T. Takahira, A. Ohtsuki, N. Chatani, Org. Lett. 2015, 17, 680.
For selected recent examples of the C–H functionalization using
modified cyclopentadienyl-rhodium(III) catalysts, see: a) T. Piou, T.
Rovis, Nature 2015, 527, 86; b) F. Romanov-Michailidis, K. F. Sedillo, J.
M. Neely, T. Rovis, J. Am. Chem. Soc. 2015, 137, 8892; c) T. Piou, T.
Rovis, J. Am. Chem. Soc. 2014, 136, 11292; d) M. D. Wodrich, B. Ye, J.
F. Gonthier, C. Corminboeuf, N. Cramer, Chem. Eur. J. 2014, 20,
15409.
Keywords: Alkynes • Anilides • Annulation • Benzo[cd]indolones
• Rhodium
[9]
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Chemistry - An Asian Journal
COMMUNICATION
COMMUNICATION
10.1002/asia.201600943
O
OR3
R2
Miho Fukui, Yu Shibata,* Yuki Hoshino,
Haruki Sugiyama, Kota Teraoka,
Hidehiro Uekusa, Keiichi Noguchi, and
Ken Tanaka*
H
(OMe)
H
R2
CO2Et
R2
Me
CpERh(III) catalyst
Me
Cl
R1
+
H
Rh
Cl
Me
EtO2
cat. AgSbF6 / cat. Cu(OAc)2¥H2
O
R1
N
O
C
RT, under air
2
O
OR3
N
Ac
CpERh(III) catalyst
O
(or ĞMeOH), ĞR3OH]
Ac
up to 73% yield
[ĞH2
Page No. – Page No.
Rhodium(III)-Catalyzed Tandem
[2+2+2] Annulation-Lactamization of
Anilides with Two Alkynoates via
Cleavage of Adjacent Two C–H or C–
H/C–O bonds
It has been established that an electron-deficient CpE-rhodium(III) complex
catalyzes the tandem [2+2+2] annulation-lactamization of acetanilides with two
alkynoates via cleavage of adjacent two C–H or C–H/C–O bonds to give densely
substituted banzo[cd]indolones. On the other hand, 3,5-dimethoxyacetanilides
reacted with two alkynoates to give dearomatized spiro compounds.