Formal Lossen Rearrangement/[3+2] Annulation Cascade Catalyzed by a Modified Cyclopentadienyl RhIII Complex

Article abstract of DOI:10.1002/chem.201801125

It has been established that a cyclopentadienyl Rh^III complex with two phenyl groups and a pendant amide moiety catalyzes the formal Lossen rearrangement/[3+2] annulation cascade of N-pivaloyl benzamides and acrylamides with alkynes leading to substituted indoles and pyrroles. Mechanistic studies revealed that this cascade reaction proceeds via not the Lossen rearrangement to form anilides or enamides but C?H bond cleavage, alkyne insertion, and the formal Lossen rearrangement.

Full text of DOI:10.1002/chem.201801125

A Journal of
Accepted Article
Title: Formal Lossen Rearrangement/[3+2] Annulation Cascade
Catalyzed by a Modified Cyclopentadienyl RhIII Complex
Authors: Takayuki Yamada, Yu Shibata, Susumu Kawauchi, Soichi
Yoshizaki, and Ken Tanaka
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To be cited as: Chem. Eur. J. 10.1002/chem.201801125
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10.1002/chem.201801125
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COMMUNICATION
Formal Lossen Rearrangement/[3+2] Annulation Cascade
Catalyzed by a Modified Cyclopentadienyl RhIII Complex
Takayuki Yamada,[a] Yu Shibata,*,[a] Susumu Kawauchi,[a] Soichi Yoshizaki,[a] and Ken Tanaka*,[a]
Abstract: It has been established that a cyclopentadienyl RhIII
complex with two phenyl groups and a pendant amide moiety
catalyzes the formal Lossen rearrangement/[3+2] annulation
cascade of N-pivaloyl benzamides and acrylamides with alkynes
leading to substituted indoles and pyrroles. Mechanistic studies
revealed that this cascade reaction proceeds via not the Lossen
rearrangement to form anilides or enamides but C–H bond cleavage,
alkyne insertion, and the formal Lossen rearrangement.
similar transformation,[3g] the [3+2] annulation products were
obtained as minor products (Scheme 1b-1). Furthermore, we
have elucidated that this cascade reaction proceeds via not the
Lossen rearrangement to form anilides,[10] which was proposed
by Li and Wang, but C–H bond cleavage, alkyne insertion, and
the formal Lossen rearrangement.
a) CpRhIII catalysts
Me
tBu
tBu Me
Me
Cl
Ph
Ph
Me
Me
Me
Cl
R2
N
R
R1
Rh
Rh
Cl
Me
Cl
Cl
R3
O
Rh
Cl
R1
2
2
O
In the area of transition-metal catalysis, a modification of
supporting ligands is important to not only improve the catalytic
activity but also control chemo-, regio-, and stereoselectivity.[1]
Although cyclopentadienyl ligands are the most historic ligands
in organometallic chemistry, structural diversity had been limited
due to difficulties of substitution and complexation without
affecting reactive functional groups. For example, in the RhIII-
catalyzed C–H bond functionalization,[2] commercially available
pentamethylcyclopentadienyl-RhIII (Cp*RhIII) complex has been
predominantly employed and modified CpRhIII complexes have
been limited to simple alkyl or phenyl substituted ones (Cpt,[3a]
Rh
Cl
[CptRhCl2]2
[Cp*Ph2RhCl2]2
2
Cl
[Cp*RhCl2]2 (R = Me)
Ph
2
[CpCF3RhCl2]2 (R = CF3)
[Cp*tBuRhCl2]2 (R = tBu)
[Cp*CyRhCl2]2 (R = Cy)
[Cp*PhRhCl2]2 (R = Ph)
[Cp(CF3)2ArRhCl2]2
[CpARhCl2]2
1a [R1 = Ph, R2, R3 = -(CH2)4-]
1b (R1 = Ph, R2 = R3 = Me)
1c (R1 = Ph, R2 = Ph, R3 = H)
1d (R1 = Ph, R2 = Bn, R3 = H)
1e (R1 = Ph, R2 = R3 = H)
1f (R1 = 3,5-Me2C6H3,
R2 = R3 = Me)
Ph
Rh
Cl
Rh
Cl
Cl
Cl
2
2
[CpCyRhCl2]2 [CpCyPh2RhCl2]2
[R = 3,5-(CF3)C6H3]
Me
Me
CO2Et
Me
iPr
EtO2C
Rh
Rh
Cl
1g [R1 = 3,5-(CF3)2C6H3,
R2 = R3 = Me]
Cl
Cl
Cl
2
2
[CpiPrRhCl2]2
[CpERhCl2]2
b-1) Lossen rearrangement/[3+2] annulation (Wang's work)
MeO
O
CpCy,[3b] CpiPr,[3c] CpCF3 [3d,e]
,
Cp*Cy,[3f] Cp*tBu [3f]
RhIII complexes) (Scheme 1a). The use of these
,
Cp*Ph,[3g] and
Cp*PhRhIII
catalyst
O
O
H
N
OPiv
N
[3h]
Cp(CF3)2Ar
R
+
R
N
H
Ph
R
Ph
P(S)Ph2
[4+2] (major)
complexes improved catalytic activity[3d,e,h,i,4] and/or regio- and
stereoselectivity.[3a-c,g,j,5] On the other hand, our group developed
the synthesis of an ethoxycarbonyl-substituted Cp ligand (CpE)
and its reductive complexation to RhCl3 (Scheme 1a). The thus
obtained electron-deficient CpERhIII complex significantly
improved the catalytic activity[4] in the C–H bond
functionalization of electron-rich arenes. Recently, it was found
that this CpERhIII complex is able to change the reaction
pathways.[6] Chang reported the [4+2] and [4+1] annulations of
N-acyloxybenzamides with enynones using Cp*Cy and CpE
ligands, respectively.[6] Very recently, our group developed
CpRhIII complexes with a pendant amide moiety [CpARhIII (1)],
which showed high catalytic activity in the sp2 and sp3 C–H
functionalization (Scheme 1a).[7] In this paper, we have
discovered that the CpARhIII complexes are also able to change
the reaction pathways and catalyze not the normal [4+2]
annulation[8] but the formal Lossen rearrangement/[3+2]
annulation[9] cascade of N-pivaloyl-benzamides and acrylamides
with alkynes (Scheme 1b-2). Although Li and Wang reported a
Ph
P(S)Ph2
P(S)Ph2
[3+2] (minor)
Lossen
rearrangement
H
N
OMe
R
O
MeOH
Ph
P(S)Ph2
H
proposed intermediate
b-2) formal Lossen rearrangement/[3+2] annulation (this work)
CpARhIII
R
O
R2
O
catalyst
OPiv
N
N
H
R1
R3
+
R1
R3
O
R2
[3+2] (major)
MeO
O
OPiv
N
Rh
N
R1
Rh
R1
MeOH
R3
R3
R2
R2
formal Lossen rearrangement
Scheme 1. (a) Modified CpRhIII catalysts and (b) RhIII-catalyzed (formal)
Lossen rearrangement/[3+2] annulation cascade.
In our previous report, the CpARhIII complexes showed high
catalytic activity toward the C–H bond functionalization of
electron- rich anilides. We anticipated that the relatively electron-
rich nature of the CpARh complexes would also facilitate the C–
H bond functionalization of electron-deficient benzamides. Thus,
the reaction of N-pivaloyl-benzamide (2a) with diphenylacetylene
(3a) was tested under the previously reported Fagnou’s
conditions[8f] using CpARhIII complex 1a bearing two phenyl
groups and a pendant pyrroridinylamide moiety instead of the
Cp*RhIII complex. Surprisingly, not the expected isoquinolinone
5aa but indole 4aa was obtained as a major product (Table 1
entry 1). To improve the yield of 4aa, screening of base was
[a]
T. Yamada, Dr. Y. Shibata, Prof. Dr. S. Kawauchi, S. Yoshizaki,
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.apc.titech.ac.jp/~ktanaka/
Supporting information for this article is given via a link at the end
of the document
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10.1002/chem.201801125
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COMMUNICATION
conducted,[11] which revealed that CsOPiv was the best one
(entry 2). Interestingly, decreasing the amount of CsOPiv
improved the ratio of 4aa/5aa but lowered conversions (entries
3–6), and thus 0.3 equiv was found to be the best amount (entry
3). Optimization of the amide moiety on the Cp ring (1b–e,
entries 7–10) revealed that the use of 1b bearing the N,N-
dimethylamide moiety gave 4aa in the highest yield (entry 7).
With regard to the aryl group on the Cp ring, the use of 3,5-
Me2C6H3 derivative 1f decreased the ratio of 4aa/5aa (entry 11)
and that of 3,5-(CF3)2C6H3 derivative 1g afforded 4aa exclusively,
but the reaction was sluggish (entry 12). In entries 5 and 12,
increasing the catalyst loadings (20 mol % Rh) lowered the ratio
of 4aa/5aa, therefore entry 7 was the best conditions. Previously
reported CpRhIII catalysts were also tested (entries 13–17).[3,4]
Substitution with the ethoxycarbonyl or phenyl group on the Cp
ring increased the ratio of 4aa/5aa (entries 13–16) but did not
exceed the ratio using 1b (entry 7). Furthermore, as diphenyl-
substituted bicyclic Cp complex was also ineffective (entry 17),
the presence of not only diphenyl groups but also the amide
moiety is important to promote the formation of 4aa. When
conducting the reaction under Ar, the product yields were
decreased (entry 18), while the addition of the Cu(II) oxidant
resulted in the comparable yield (entry 19). These facts suggest
that CpARh(I) was oxidized by air to regenerate CpARh(III).
[a] 1 (0.0025 mmol), base (0.030-0.20 mmol), 2a (0.10 mmol), 3a (0.11 mmol),
and solvent (0.5 mL) were used. [b] Isolated yield. [c] 1 (0.0050 mmol) was
used. [d] At 60 °C. [e] Under Ar. [f] Cu(OAc)2•H2O (0.21 mmol) was added.
O
R2
CO2Me
2.5 mol % 1b
CsOPiv (0.3 equiv)
N
OPiv
R1
N
H
R3
+
R1
MeOH, RT, 16 h
under air
H
R2
R2
2
3
4
(1.1 equiv)
CO2Me
N
CO2Me
N
CO2Me
N
(H) R
R
Ph
Ph
Ph
R
Ph
4aa (R = H) / 78%
4ba (R = Me) / 82% (22 h) 4ja (R = OMe) / 77% (rs = 64:36) 4pa (R = OMe) / 61%
Ph
Ph
(R) H
R
4 (4')
4ia (R = Me) / 70% (rs = 95:5)
4oa (R = Me) / 79% (22 h)
4ca (R = OMe) / 90%
4da (R = F) / 66%
4ea (R = Cl) / 73%
4fa (R = Br) / 71%
4ka (R = F) / 57% (rs = 29:71)
4la (R = Cl) / 55% (rs = 67:33)
4ma (R = CF3) / 33% (rs = >20:1)
4na (R = NO2) / 28% (rs = 75:25)
Me
CO2Me
N
Ph
4ga (R = CO2Me) / 56%
4ha (R = NO2) / 28%
Ph
4qa / 73%
CO2Me
CO2Me
CO2Me
N
N
N
Ar
nPr
Ph
MeO
Ar
4cb / 87% (22 h)
MeO
MeO
nPr
Ar
4cc / 71% (34 h)[a]
4cd (4cd') / 94%
(rs = 55:45)
(Ar = 4-MeC6H4)
(Ar = 4-OMeC6H4)
CO2Me
CO2Me
CO2Me
N
N
N
Ph
Ph
Ph
[(CH2)3Cl]
MeO
MeO
Me
MeO
(CH2)3Cl (Ph)
4cg (4cg') / 67%
(rs = 92:8)
CO2Me
nBu
4ce / 84%[a]
4cf (4cf') / 65%
Table 1. Optimization of reaction conditions.[a]
(rs = 90:10)
CO2Me
CO2Me
O
O
OMe
Ph
2.5 mol% [Rh2]
base (0–2 equiv)
O
Ph
N
N
N
Ph
Ph (Cy)
Ph (tBu)
OPiv
NH
N
N
H
+
+
MeO
MeO
MeO
MeOH, RT, 16 h
under air
Ph
Cy (Ph)
tBu (Ph)
OH
Ph
4ch / 84%
4ci (4ci') / 90% (45 h)
4cj (4cj') / 27% (36 h)[a,b]
Ph
5aa
Ph
4aa
2a
3a
(rs = 87:13)
(rs = 95:5)
(1.1 equiv)
CO2Me
N
CO2Me
N
Entry
[Rh2]
Base (equiv)
Yield [%][b]
Ph (SiMe3)
Me (Cy)
MeO
MeO
4aa
45
57
66
49
5aa
18
SiMe3 (Ph)
Cy (Me)
4ck (4ck') / 74% (45 h)
4cl (4cl') / 67%a
1
2
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
CsOAc (2)
CsOPiv (2)
CsOPiv (0.3)
CsOPiv (0.2)
CsOPiv (0.1)
none
(rs = 93:7)
(rs = 72:28)
23
Scheme 2. Scope of indole synthesis. 1b (0.0050 mmol), 2 (0.022 mmol), 3
(0.20 mmol), CsOPiv (0.060 mmol), and MeOH (1.0 mL) were used. Cited
yields were of the isolated products. [a] NaOAc was used instead of CsOPiv.
[b] At 40 °C.
3
23
4
26
5
28 (57[c])
0 (21[c])
The scope of this indole synthesis was shown in Scheme 2.
With respect to N-pivaloyl-benzamides, introduction of electron-
donating groups (2b and 2c) at the para-position on the benzene
ring improved the yield of 4, while that of an electron-
withdrawing group (2d–2h) decreased the yield of 4. The
reactions of meta-substituted benzamides 2i–p afforded 4ia–pa
in reasonable yields, although regioselectivities were moderate
in some cases. Notably, 4,6-dimethyl-substituted indole 4oa was
obtained from benzamide 2o in higher yield than from 3,5-
dimethylacetanilide (79% vs. 44%[4e] yield). Ortho-substitued
benzamide 2q also reacted with 3a to give 4qa in good yield.
With respect to alkynes, not only 3a but also a variety of
symmetrical and unsymmetrical alkynes 3b–l could be employed
to give indoles 4cb–cl with good yields and regioselectivity,
although the reactivity of sterically demanding 3j was low. When
using 3c, 3e and 3l, the use of NaOAc instead of CsOPiv
improved the product yields. Importantly, silylindoles 4ck/4ck’
were obtained in good yield without formation of desilylated
6
0
78
0
7
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
CsOPiv (0.3)
20
8
71
16
9
40
29
10
11
12
13[d]
14
15
16
17
18[e]
19[e,f]
56
40
70
22
1g
39 (62[c])
0 (12[c])
[Cp*RhCl2]2
[CpERhCl2]2
[Cp*PhRhCl2]2
0
74
50
25
16
82
[Cp*Ph2RhCl2]2
31
49
[CpCy-Ph2RhCl2]2
29
52
1b
1b
44
11
70
28
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10.1002/chem.201801125
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COMMUNICATION
products under the present basic reaction conditions. This is
advantageous because the [3+2] annulation of acetanilide with
3k using the Lewis acidic cationic CpERhIII catalyst afforded a
significant amount of the desilylated products.[4e]
the present cascade process, the reactions of 8a,b and 9 with
3a were conducted under the standard conditions (condition A,
Scheme 5a). However, 4aa was not obtained at all. On the
contrary, 4aa and 4aa-tBu[4e] were generated from 8a and 8b,
respectively, by using the CpERhIII catalyst, although the yield of
4aa was low (condition B, Scheme 5a). These results indicate
that 8 and 9 are not involved in the catalytic cycle and
demonstrate the synthetic utility of the present cascade process,
in which N-pivaloyl-benzamides could be employed as less
reactive methyl N-arylcarbamate equivalents.
The present cascade reaction could be applied to the
synthesis of alkyl-substituted and heterole-fused pyrroles, which
has not been accomplished by the [3+2] annulation using
unstable alkyl-substituted enamides[12] and aminoheteroles[13]
(Scheme 3). Various α,β-disubstituted- (6a–c) and α-methyl-
substituted (6d) N-pivaloyl-acrylamides reacted with 3a by using
NaOAc as a base to give pyrroles 7aa–da in moderate to good
yields. Increasing the amount of 6 improved the yields of 7ba
and 7da. α-Phenyl-substituted one (6e) could also be employed
for this reaction, while β-substituted acrylamide 6f failed to react
with 3a. Heterolecarbamides 6g and 6h also reacted with 3a to
give heterole-fused pyrroles 7ga and 7ha, although their yields
were low to moderate. Unsymmetrical alkynes 3d–g could also
be employed, although regioselectivities were low.
To gain mechanistic insight into this cascade process, the
following experiments were conducted. Treatment of 2a under
condition A afforded carbamate 8a,[10] while no reaction was
observed in the absence of 1b and replacing 1b with
[Cp*RhCl2]2 or RhCl3•nH2O (Scheme 5b). The Lossen
rearrangement indeed proceeded to give 8a under condition A,
but no deuterium incorporation was observed for 8a in CD3OD
(Scheme 5c). Combining this result and the result shown in
Scheme 5a clearly supports the absence of 8a and 9 in the
catalytic cycle. In sharp contrast, partial deuterium incorporation
was observed for only the recovered substrate 2a-d in CD3OD
(Scheme 5d).
CO2Me
R3
2.5 mol % 1b
NaOAc (0.3 equiv)
O
R1
R2
R1
R2
OPiv
N
N
H
R3
+
MeOH, RT, 16 h
under air
R4
R4
H
7
6
3
(1.1 equiv)
(a)
H
N
Ph
Ph
OR
CO2Me
N
CO2Me
N
CO2Me
N
CO2Me
N
CO2Me
N
3a
Me
Me
Me
Ph
condition A
2.5 mol % 1b
O
Ph
Ph
Ph
Ph
Ph
O
OR
Ph
8a (R = Me)
8b (R = tBu)
(1.1 equiv)
CsOPiv (0.3 equiv)
MeOH, RT, 16 h, under air
Ph
7aa / 64%
CO2Me
Ph
7ba / 52% (65%[a]
CO2Me
Ph
Ph
Ph
N
)
7ca / 61%
7da / 56% (64%[a]
)
7ea / 46%[a][b]
condition B
2.5 mol % [CpERhCl2]2
10 mol % AgSbF6
or
CO2Me
CO2Me
Ph
N
•
N
N
S
N
N
4aa / 0% (condition A, from 8a,b and 9)
4aa / 30% (condition B, from 8a)
4aa-tBu (R = tBu) / 72%
20 mol % Cu(OAc)2•H2O
acetone, RT, 16 h, under air
Ph
Ph
Ph
Ph (Ar)
O
N
Me
Me
Ph
7fa / 0%
Ph
Ph
Ar (Ph)
9 (1.1 equiv)
(condition B, from 8b, ref 4e)
7ad (7ad') / 62%[a][b]
7ga / 49%
7ha / 14%
(Ar = 4-OMeC6H4, rs = 51:49)
(b)
O
H
N
CO2Me
CO2Me
CO2Me
CO2Me
condition A
OMe
OPiv
N
N
N
N
N
H
Ph
[(CH2)3Cl]
Ph (Me)
Ph (nBu)
Ph (Me)
O
N
Me
8a / 74%
(0%, without 1b)
nBu (Ph)
Me (Ph)
2a
(CH2)3Cl (Ph)
Me (Ph)
7ae (7ae') / 28%[a,b]
(rs = 50:50)
7af (7af') / 37%[a][b]
(rs = 70:30)
7ag (7ag') / 32%
(rs = 63:37)
7ge (7ge) / 43%[a,b]
(rs = 57:43)
(0%, [Cp*RhCl2]2 instead of 1b)
(0%, RhCl3•nH2O instead of 1b)
(c)
(d)
D
N
condition A
(in CD3OD)
H
N
Scheme 3. Scope of pyrrole synthesis. 1b (0.0050 mmol), 6 (0.22 mmol), 3
(0.20 mmol), NaOAc (0.060 mmol), and MeOH (1.0 mL) were used. Cited
yields were of the isolated products. [a] 6 (2 equiv) was used. [b] 1 (0.020
mmol) was used.
OMe
OMe
OPiv
O
O
H
H/D
8a
8a
98% recov. (0% D)
D
N
condition A
(in CD3OD)
O
O
OMe
OPiv
N
+
Application to the synthesis of 7-aminoindoles, which show
5-HT6 receptor affinity,[14] is shown in Scheme 4.
Aminobenzamide 2r, obtained by the ortho-C–H amination of
2e,[15] reacted with 3a to give 7-morphorinylindole 4ra. As the
ortho-C–H amination is possible only with benzamides, not
acetanilides, this example clearly demonstrated more pronoused
synthetic advantage of the present cascade reaction.
N
H
O
D
H/D
H
H/D
2a-d
8a
2a
63% recov. (12% D)
12% (0% D)
Scheme 5. (a) RhIII-catalyzed reactions of methyl N-phenylcarbamates (8) and
isocyanate 9 with 3a. (b) Mechanistic studies.
Based on the above experiments (Schemes 5), possible
mechanisms for the formation of 4aa are proposed in Scheme 6.
As with the [4+2] annulation of N-acyloxybenzamide 2a with
alkyne 3a,[8c] cleavage of C–H bond of 2a with CpARhIII followed
by insertion of 3a furnishes rhodacycle B via A. Then, the formal
Lossen rearrangement furnishes isocyanate C. Addition of
MeOH furnishes rhodacycle D, and subsequent reductive
elimination affords 4aa and the CpARhI complex, which is
oxidized by air to regenerate the CpARhIII complex. DFT
calculation supports the formal Lossen rearrangement via a
nitrene intermediate as shown in the Supporting Information
O
O
(3 equiv)
Ph
Ph
3a
N
5 mol % 1c
30 mol % NaOAc
CO2Me
N
H
O
N
O
OPiv
OPiv
N
N
Ph
H
H
MeOH, RT, 16 h
under air
Cl
Cl
Cl
Ph
4ra / 35%
ref. 15
2e
2r
Scheme 4. Application to the synthesis of 7-aminoindole 4ra.
In order to clarify whether the corresponding Lossen
rearrangement products 8 and isocyanate 9 are intermediates of
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10.1002/chem.201801125
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COMMUNICATION
(Scheme S1).[16] Alternatively, the pathway via rhodacycles E
and F is also capable of affording 4aa. However, as no
deuterium incorporation was observed for 8 under condition A in
CD3OD (Scheme 5d), this pathway can be excluded.
M. Neely, T. Rovis, J. Am. Chem. Soc. 2014, 136, 2735; e) F.
Romanov-Michailidis, K. F. Sedillo, J. M. Neely, T. Rovis, J. Am. Chem.
Soc. 2015, 137, 8892; f) T. Piou, T. Rovis, Nature 2015, 527, 86; g) B.
Li, J. Yang, H. Xu, H. Song, B. Wang, J. Org. Chem. 2015, 80, 12397;
h) T. Piou, F. Romanov-Michailidis, M. Romanova-Michaelides, K. E.
Jackson, N. Semakul, T. D. Taggart, B. S. Newell, C. D. Rithner, R. S.
Paton, T. Rovis, J. Am. Chem. Soc. 2017, 139, 1296.
In conclusion, we have established that a cyclopentadienyl
RhIII complex with two phenyl groups and a pendant amide
moiety catalyzes the formal Lossen rearrangement/[3+2]
annulation cascade of N-pivaloyl benzamides and acrylamides
with alkynes leading to substituted indoles and pyrroles.
Mechanistic studies revealed that this cascade reaction
proceeds via not the Lossen rearrangement to form anilides or
enamides but C–H bond cleavage, alkyne insertion, and the
formal Lossen rearrangement.
[4]
a) Y. Takahama, Y. Shibata, K. Tanaka, Org. Lett. 2016, 18, 2934; b) E.
Kudo, Y. Shibata, M. Yamazaki, K. Masutomi, Y. Miyauchi, M. Fukui, H.
Sugiyama, H. Uekusa, T. Satoh, M. Miura, K. Tanaka, Chem. Eur. J.
2016, 22, 14190; c) Y. Takahama, Y. Shibata, K. Tanaka, Chem. Eur. J.
2015, 21, 9053; d) M. Fukui, Y. Shibata, Y. Hoshino, H. Sugiyama, K.
Teraoka, H. Uekusa, K. Noguchi, K. Tanaka, Chem. Asian J. 2016, 11,
2260; e) Y. Hoshino, Y. Shibata, K. Tanaka, Adv. Synth. Catal. 2014,
356, 1577; f) M. Fukui, Y. Hoshino, T. Satoh, M. Miura, K. Tanaka, Adv.
Synth. Catal. 2014, 356, 1638; g) Y. Shibata, K. Tanaka, Angew. Chem.
Int. Ed. 2011, 50, 10917; Angew. Chem. 2011, 123, 11109.
For seminal works of asymmetric reactions using chiral CpRhIII
catalysts, see: a) B. Ye, N. Cramer, Sscience 2012, 338, 504; b) T. K.
Hyster, L. Knoerr, T. R. Ward, T. Rovis, Science 2012, 338, 500. For a
review, see: c) B. Ye, N. Cramer, Acc. Chem. Res. 2015, 48, 1308.
a) S. Y. Hong, J. Jeong, S. Chang, Angew. Chem. Int. Ed. 2017, 56,
2408; Angew. Chem. 2017, 129, 2448. Rovis reported the change of
the reaction pathways between cyclopropanation and carboamination
by using CpiPr and Cp*tBuRhIII catalysts, respectively. See ref 3c,f.
S. Yoshizaki, Y. Shibata, K. Tanaka, Angew. Chem. Int. Ed. 2017, 56,
3590; Angew. Chem. 2017, 129, 3644.
cat. [Rh]IIIX2
MeOH
2a
9
8a
–PivOH
[Rh]IIIX2
[5]
[6]
–2HX
O
•
O
OMe
O
MeOH
O
tBu
O
tBu
tBu
N
N
N
–PivOH
O
[Rh]
O
[Rh]
[Rh]
E
A
F
3a
3a
O
•
O
OMe
O
O
tBu
O
[7]
[8]
N
N
MeOH
N
O
O
[Rh]
[Rh]
[Rh]
Ph
–PivOH
Ph
For selected examples, see: a) S. Mochida, N. Umeda, K. Hirano, T.
Satoh, M. Miura, Chem. Lett. 2010, 39, 744; b) G. Song, D. Chen, C.-L.
Pan, R. H. Crabtree, X. Li, J. Org. Chem. 2010, 75, 7487; c) T. K.
Hyster, T. Rovis, J. Am. Chem. Soc. 2010, 132, 10565; d) N. Guimond,
C. Gouliaras, K. Fagnou, J. Am. Chem. Soc. 2010, 132, 6908.
Ph
Ph
Ph
Ph
B
D
C
I
–
[Rh]
[Rh] = CpARh
4aa
Scheme 6. Possible mechanisms for formation of 4aa.
[9]
For selected examples, see: a) D. R. Stuart, M. Bertrand-Laperle, K. M.
N. Burgess, K. Fagnou, J. Am. Chem. Soc. 2008, 130, 16474; b) J.-L.
Chen, G.-Y. Song, C.-L. Pan, X.-W. Li, Org. Lett. 2010, 12, 5426; c) D.
R. Stuart, P. Alsabeh, M. Kuhn, K. Fagnou, J. Am. Chem. Soc. 2010,
132, 18326; d) M. P. Huestis, L. Chan, D. R. Stuart, K. Fagnou, Angew.
Chem. Int. Ed. 2011, 50, 1338; Angew. Chem. 2011, 123, 1374.
Acknowledgements
This work was supported partly by ACT-C (No.
JPMJCR1122YR) from JST (Japan) and Grants-in-Aid for
Scientific Research (No. JP26102004), for Research Activity
Start-up (No. 15H06201), and for Young Scientists (No.
17K14481) from JSPS (Japan). We thank Umicore for generous
support in supplying RhCl3•nH2O. The DFT calculations were
carried out on the TSUBAME2.5 supercomputer at the Tokyo
Institute of Technology, Tokyo, Japan, and on the
supercomputer at the Research Center for Computational
Science, Okazaki, Japan.
[10] The Lossen rearrangement by-products from N-acyloxybenzamides
were observed at 60 °C in the presence of the Cp*RhIII catalyst and
base. See: a) K. D. Collins, F. Glorius, Tetrahedron 2013, 69, 7817; b)
N. J. Webb, S. P. Marsden, S. A. Raw, Org. Lett. 2014, 16, 4718; c) N.
Semakul, K. E. Jackson, R. S. Paton, T. Rovis, Chem. Sci. 2017, 8,
1015; d) J.-Q. Wu, S.-S. Zhang, H. Gao, Z. Qi, C.-J. Zhou, W.-W. Ji, Y.
Liu, Y. Chen, Q. Li, X. Li, H. Wang, J. Am. Chem. Soc. 2017, 139, 3537.
[11] The leaving groups and solvents were also screened, but the yield of
4aa was not improved. See the Supporting Information.
[12] The synthesis of pyrroles has been limited to the use of stable
enamides bearing aryl or electron-withdrawing groups. See: a) S.
Rakshit, F. W. Patureau, F. Glorius, J. Am. Chem. Soc. 2010, 132,
9585; b) B. Li, N. Wang, Y. Liang, S. Xu, B. Wang, Org. Lett. 2013, 15,
136; c) L. Wang, L. Ackermann, Org. Lett. 2013, 15, 176; f) M.-N. Zhao,
Z.-H. Ren, Y.-Y. Wang, Z.-H. Guan, Org. Lett. 2014, 16, 608; g) W. Yu,
W. Zhang, Y. Liu, Y. Zhou, Z. Liu, Y. Zhang, RSC Adv. 2016, 6, 24768;
h) D. M. Lade, A. B. Pawar, Org. Chem. Front. 2016, 3, 836. See also
refs 4e, 9c, and 9d.
Keywords: Annulation • Cyclopentadienyl Complexes • C-H
Functionalization • Lossen Rearrangement • Rhodium
[1]
[2]
For a selected recent review, see: M. Stradiotto, R. J. Lundgren, Ligand
Design in Metal Chemistry: Reactivity and Catalysis, Wiley, 2016.
For selected recent reviews, see: a) Y. Yang, K. Li, Y. Cheng, D. Wan,
M. Li, J. You, Chem. Commun. 2016, 52, 2872; b) C. G. Newton, D.
Kossler, N. Cramer, J. Am. Chem. Soc. 2016, 138, 3935; c) T. Gensch,
M. N. Hopkinson, F. Glorius, J. Wencel-Delord, Chem. Soc. Rev. 2016,
45, 2900; d) T. Sperger, I. A. Sanhueza, I. Kalvet, F. Schoenebeck,
Chem. Rev. 2015, 115, 9532.
[13] Stability and availability of aminoheteroles are lower than anilides. See:
F. M. Albini, R. Oberti, P. Caramella, J. Chem. Res., Synop. 1983, 4.
[14] S. M. Bromidge, C. N. Johnson, G. J. MacDonald, M. Thompson, D. R.
Witty, PCT Int. Appl. WO 03/013510 A1, 2003.
[15] C. Grohmann, H. Wang, F. Glorius, Org. Lett. 2012, 14, 656.
[16] During revision of our manuscript, the Cp*RhIII-catalyzed C–H
olefination of N-pivaloxyl benzamides with α,α-difluoromethylalkynes
via the formal Lossen rearrangement was reported. See: C-Q. Wang, Y.
Zhang, C. Feng, Angew. Chem. Int. Ed. 2017, DOI:
10.1002/anie.201708505.
[3]
For selected examples of modified CpRhIII catalysts, see: a) T. K.
Hyster, T. Rovis, Chem. Sci. 2011, 2, 1606; b) M. D. Wodrich, B. Ye, J.
F. Gonthier, C. Corminboeuf, N. Cramer, Chem. Eur. J. 2014, 20,
15409; c) T. Piou, T. Rovis, J. Am. Chem. Soc. 2014, 136, 11292; d) J.
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10.1002/chem.201801125
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
O
Takayuki Yamada, Yu Shibata,* Susumu
Kawauchi, Soichi Yoshizaki, Ken
Tanaka*
OPiv
N
H
R1
MeO
O
Ph
CpARhIII
catalyst
OPiv
O
NMe2
H
+
R2
N
O
MeOH
N
R1
Ph
Rh
R1
R3
O
Rh
Cl
RT, air
Cl
R3
R2
R2
2
[CpARhCl2]2
Page No. – Page No.
R3
formal Lossen rearrangement/[3+2] annulation cascade
It has been established that a cyclopentadienyl RhIII complex with two phenyl
groups and a pendant amide moiety catalyzes the formal Lossen
rearrangement/[3+2] annulation cascade of N-pivaloyl benzamides and acrylamides
with alkynes leading to substituted indoles and pyrroles. This cascade reaction
proceeds via not the Lossen rearrangement to form anilides or enamides but C–H
bond cleavage, alkyne insertion, and the formal Lossen rearrangement.
Formal Lossen Rearrangement/[3+2]
Annulation Cascade Catalyzed by a
Modified Cyclopentadienyl RhIII
Complex
This article is protected by copyright. All rights reserved.