A Cp?CoI2-dimer as a precursor for cationic Co(iii)-catalysis: Application to C-H phosphoramidation of indoles

Article abstract of DOI:10.1039/c4cc10284c

C2-selective indole C-H phosphoramidation was achieved through improved Cp?Co(iii) catalysis. A cationic Co(iii) species generated in situ from a Cp?CoI₂-dimer showed the best catalytic activity, giving phosphoramidated indoles in 60-86% yield.

Full text of DOI:10.1039/c4cc10284c

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A Cp*CoI2-dimer as a precursor for cationic Co(III)-
catalysis: application to C-H phosphoramidation of
indoles
Cite this: DOI: 10.1039/x0xx00000x
Bo Sun,a Tatsuhiko Yoshino,ab Shigeki Matsunaga,* ab and Motomu Kanai*a
Received 00th December 2014,
Accepted 00th January 2015
DOI: 10.1039/x0xx00000x
www.rsc.org/
C2-Selective indole C-H phosphoramidation was achieved
under improved Cp*Co(III) catalysis. A cationic Co(III)
species generated in situ from a Cp*CoI2-dimer showed the
best catalytic activity, giving phosphoramidated indoles in
60-86% yield.
Me
Me
X
Me
Me
Me
Co
Me
Co
X
Me
Me
Me
Me
Me
Me
Me
Me
(PF6)2
Me
Co
X
Co
Me
CO
Me
X
Me
Me
Me
1c : X = I, [Cp*CoI2]2
1d : X = Cl, [Cp*CoCl2]2
I
Transition metalꢀcatalyzed CꢀH bond functionalization reactions are
powerful and potentially superior to traditional organic reactions
using stoichiometric activating reagents. Among the various
transition metal catalysts developed for CꢀH bond functionalization
reactions, cationic Cp*Rh(III) and Cp*Ir(III) complexes are widely
applied for various CꢀC, CꢀN, and many other CꢀX bondꢀforming
reactions.1 Despite their high catalytic activity and broad reaction
scope, however, the use of expensive and precious rhodium and
iridium metal sources is somewhat disadvantageous. Thus, the
development of an alternative catalyst with readily available base
metal sources is highly desirable.2 Since our first report on the utility
of a cationic Cp*Co(III)ꢀarene complex 1a in 2013 (Fig. 1),3 we and
others have expended tremendous effort to broaden the scope of
Co(III)ꢀcatalysis.4,5 The development of a readily available, stable,
and easyꢀtoꢀhandle catalyst is in high demand to further enhance the
application of cationic Cp*Co(III) catalysis. Toward this aim, we
previously reported the synthesis and application of a Cp*Co(CO)I2
complex.6 The Cp*Co(CO)I2 complex 1b was useful for generating
an active cationic Co(III) species in situ. Safety issues, however,
remained problematic; toxic carbon monoxide was inevitably
released during the reaction process, and all reaction vessels had to
be handled carefully. Thus, further studies are needed to avoid the
safety issues in future industrial applications of the Co(III) catalysis.
Herein, we describe the utility of an airꢀstable dimeric [Cp*CoI2]2
complex 1c, which is readily available in multiꢀgram quantity. The
dimeric [Cp*CoI2]2 1c showed superior performance in comparison
with previously reported Co(III) complexes.
I
1a
1b
Fig. 1 Structures of Cp*Co(III) complexes 1a-1d.
phosphoramidation strategy is less studied. Recently, a couple of Cꢀ
phosphoramidation reactions with phosphoryl azides were
H
disclosed under transition metal catalysis.10ꢀ13 Among them, the
Cp*Ir(III)ꢀbased strategy pioneered by Chang and coworkers
provides a highly efficient approach for the synthesis of various
phosphoramidates from arenes.12 Because indoles were not used in
recent reports of Cp*Ir(III)ꢀcatalysis, we selected CꢀH
phosphoramidation reaction of indoles 2 with phosphoryl azides 3 as
a target reaction to broaden the scope of CꢀH phosphoramidation
reactions.14
Initial optimization studies using indole 2a and azide 3a15 are
summarized in Table 1. The original cationic Cp*Coꢀarene complex
1a did not afford any product (entry 1). In situ generation of an
active cationic Cp*Co(III) species was effective, and the
combination of Cp*Co(CO)I2 1b and AgSbF6 gave the desired
product 4aa, albeit in moderate yield (entry 2, 34%). The yield was
improved by changing the catalyst precursor to a dimeric iodide
complex [Cp*CoI2]2 1c (50%, entry 3), while [Cp*CoCl2]2 1d3
resulted in poor yield (4%, entry 4).16 Because dimeric [Cp*CoI2]2
1c was synthesized by thermal decarbonylation of 1b in a gram
scale,17 it was necessary to carefully perform the decarbonylation
process. Once dimeric [Cp*CoI2]2 1c was obtained, however, 1c
itself was airꢀstable and easyꢀtoꢀhandle. Other silver salts (entries 5ꢀ
6) as well as other solvents did not improve the yield. In contrast to
our previous studies on indole functionalization,4a,6 the addition of
KOAc was not effective (entry 7). While higher temperature
decreased the yield, probably due to the thermal instability of 3a
(entries 8ꢀ9), a higher concentration improved the yield (entries 10ꢀ
Phosphoramidates are important structural units found in many
biologically active compounds,7 such as agrocin 84,8a microcin C7,8b
and phosmidosine antibiotics,8c and proꢀnucleotides as prodrugs of
antiviral and antitumor agents.8d In addition, phosphoramidates are
useful synthetic intermediates for synthesizing various nitrogenꢀ
containing
heterocycles.9
Conventional
methods
for
phosphoramidates rely on PꢀN bond formation, while the CꢀH bond
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Table 1 Optimization of reaction conditionsa
Table 2 Substrate scope of phosphoramidation of indoles 2 with phosphoryl
azides 3a
O
Co cat.
Ag salt
O
O
NP(OPh)2
H
1c (5 mol %)
AgSbF6
(20 mol %)
O
+
N3 P(OPh)2
N
N
X
NP(OAr)2
H
X
+
N3 P(OAr)2
1,4-dioxane
36 h
N
N
N
N
2a
3a
4aa
N
N
2
3
1,4-dioxane
60 °C, 36 h
4
N
N
N
N
Co cat.
(x mol %)
Ag salt
(y mol %)
Conc. Yield
(%)b
(M)
Temp
(°C)
X
Entry
O
O
NP(OPh)2
NP(OPh)2
0
34
50
4
trace
5
45
17
1
2
3
4
5
6
1a (10)
1b (10)
1c (5)
1d (5)
1c (5)
1c (5)
none
60
60
60
60
60
60
60
80
100
60
60
60
60
60
60
60
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
1.0
2.0
2.0
2.0
2.0
2.0
2.0
H
H
N
N
N
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgPF6 (20)
AgBF4 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
AgSbF6 (20)
none
X = OMe 4ba 86%
N
N
4aa 80%
N
Cl
Br
4ca 66%
4da 60%
X
O
7c 1c (5)
X = Me
4ea 81%
4fa 76%
4ga 70%
4ha 85%
4ia 75%
NP(OPh)2
H
OMe
F
Cl
8
9
1c (5)
1c (5)
N
0
79
10 1c (5)
11 1c (5)
12 none
13 1c (5)
14 Co(acac)3 (10)
15 Co(NH3)6Cl3 (10) none
16 CoI2 (10)
AgSbF6 (20)
N
86 (80)d
N
Br
CO2Me 4ja 75%
0
trace
0
0
0
O
O
none
NP(OAr1)(OAr2)
NP(OPh)2
H
H
N
N
X
N
N
N
N
a Reactions were run using 2 equiv of 2a. b Yield of 4aa was determined by
1H NMR analysis of crude reaction mixture with an internal standard. c KOAc
X = Me
4ka 78%
Ar1, Ar2 = 4-MeO-C6H4
Ar1 = Ph; Ar2 = 4-Cl-C6H4
d
4ab 77%
4ac 74%
(20 mol %) was added.
Isolated yield of 4aa was determined after
OBn 4la 74%
F
Cl
purification by silica gel column chromatography.
4ma 77%
4na 82%
11). In entry 11, 4aa was obtained in 86% yield (80% isolated yield)
at 2.0 M in 1,4ꢀdioxane at 60 °C. The reaction was completely C2ꢀ
selective, and no regioisomeric product was detected under the
optimized reaction conditions. Negative control experiments in
entries 12ꢀ13 indicated that both complex 1c and AgSbF6 are
essential to promote the reaction. Neither other Co(III)ꢀsalts nor in
situꢀgenerated cationic Co(II)ꢀspecies promoted the reaction (entries
14ꢀ16), suggesting that the use of cationic Co(III) species was
essential to promote the reaction.
aReactions were run using 2 (0.80 mmol), 3 (0.40 mmol), 1c (5 mol %), and
AgSbF6 (20 mol %) in 1,4ꢀdioxane (2.0 M) at 60 °C for 36 h. Isolated yield
of 4 was determined after purification by silica gel column chromatography.
[Cp*CoI2]2 1c
+ 2AgSbF6 + 2
O
NHP(OPh)2
N
The substrate scope of the phosphoramidation of indoles under the
optimized conditions is summarized in Table 2.18 Various indoles
bearing electronꢀdonating (Me, MeO, and BnO) and electronꢀ
withdrawing groups (halogen and CO2Me) at either the C4ꢀ, C5ꢀ, or
C6ꢀposition afforded products 4aa–4na in 60–86% yield. These
results clearly indicated good chemoselectivity of the present
Cp*Co(III) catalysis. The C2ꢀselectivity should arise from the inner
sphere mechanism involving directing groupꢀassisted CꢀH bond
metalation. Thus, our reaction conditions are complementary to the
intraꢀ and intermolecular alkane amidation reaction via an
outersphere mechanism under Coꢀ and Ruꢀporphyrin catalysis.11b
With regard to the scope of the phosphoryl azide, an electronꢀ
donating MeOꢀsubstituent and an electronꢀwithdrawing Clꢀ
substituent were compatible (4ab, 77%; 4ac, 74%). On the other
hand, diethyl phosphoryl azide did not afford desired
phosphoramidation product.
A plausible reaction mechanism is depicted in Scheme 1, based on
the previously reported Cp*Co(III)ꢀcatalyzed CꢀH bond
functionalization reaction of indoles4 and the mechanistic studies by
Chang and coworkers on the Cp*Rh(III)ꢀcatalyzed19 CꢀH bond
amidation reactions. Initial halide abstraction from [Cp*CoI2]2 1c by
AgSbF6 in the presence of the pyrimidylꢀprotected indole 2 would
form cationic complex I. A CꢀH bond activation step to afford
metalacycle II would proceed via either electrophilic aromatic
substitution mechanism or concerted metalationꢀdeprotonation
N
N
4
H
N
path A
[Co]-LN
N
N
2
+ H+
H+
I
[Co] = [Cp*CoIII]2+
O
N
P(OPh)2
N
[Co]
N
2
4
N
[Co]
N
N
II
N
IV
path B
N
O
N
N
P(OPh)2
O
N2
[Co]
N
N3 P(OPh)2
3
N
N
III
Scheme 1 Plausible catalytic cycle.
(CMD)20 assisted by some basic functional groups. Coordination of
phosphoryl azide 3 (III) followed by CꢀN bond formation with
release of N2 gave IV. Although stepwise CꢀN bond formation
2 | J. Name., 2012, 00, 1-3
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through a Rh(V)ꢀnitrenoid species rather than concerted CꢀN bond
formation was supported in the Cp*RhIIIꢀcatalyzed amidation
reaction,18 we cannot yet conclude which mechanism is plausible,
either nitrenoid formation or concerted substitution, for the
Cp*Co(III) catalysis. Because there is no evidence for the formation
of a high valent, possibly unstable, Co(V) intermediate under the
present reaction conditions, further studies are required to clarify the
reaction pathway. Protonation by the acidic proton released in the Cꢀ
H bond metalation step (path A) or direct deprotonation from a CꢀH
bond of another substrate 2 (path B) would dissociate the product 4.
In conclusion, an improved cationic Cp*Co(III) catalyst generated
from [Cp*CoI2]2 1c and AgSbF6 exhibited higher catalytic activity
than those from other Cp*Co(III)ꢀcomplexes. Directing groupꢀ
assisted CꢀH bond metalation realized high regioꢀ and
chemoselectivity under mild conditions, and the C2ꢀselective CꢀH
bond phosphoramidation reaction of 2ꢀpyrimidylꢀprotected indoles
proceeded in 60–86% yield. Studies of the reaction mechanism as
well as further applications of Cp*Co(III)ꢀcatalysis are actively
ongoing in our group.
McCloskey, J. Org. Chem., 1993, 58, 854; (d) S. R. Wagner, V. V.
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9
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reactions using azides: a) S. H. Kim, S. H. Park, J. H. Choi and S.
Chang, Chem. Asian J., 2011,
Chem., 2010, , 3831.
6, 2618; b) T. G. Driver, Org. Biomol.
8
11 Early works under Coꢀ and Ruꢀporphyrin catalysis; (a) W. Xiao, C.ꢀY.
Zhou and C.ꢀM. Che, Chem. Commun., 2012, 48, 5871; (b) W. Xiao,
J. Wei, C.ꢀY. Zhou and C.ꢀM. Che, Chem. Commun., 2013, 49, 4619.
12 (a) H. Kim, J. Park, J. G. Kim and S. Chang, Org. Lett., 2014, 16
,
5466; For a similar work from other group, see also (b) C. Pan, N.
Jin, H. Zhang, J. Han and C. Zhu, J. Org. Chem., 2014, 79, 9427.
13 For selected leading examples of other amidation reactions under
Cp*Ir(III) and Cp*Rh(III)ꢀcatalysis, see: (a) J. Y. Kim, S. H. Park, J.
Ryu, S. H. Cho, S. H. Kim and S. Chang, J. Am. Chem. Soc., 2012,
134, 9110; (b) J. Ryu, K. Shin, S. H. Park, J. Y. Kim and S. Chang,
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Chang, Angew. Chem., Int. Ed., 2013, 52, 8031; (d) J. Ryu, J. Kwak,
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T. Kang, Y. Kim, D. Lee, Z. Wang and S. Chang, J. Am. Chem. Soc.,
2014, 136, 4141.
Notes and references
Graduate School of Pharmaceutical Sciences, The University of Tokyo,
a
7ꢀ3ꢀ1 Hongo, Bunkyoꢀku, Tokyo 113ꢀ0033, Japan.
b
ACTꢀC, Japan Science and Technology Agency, Hongo, Bunkyoꢀku,
Tokyo 113ꢀ0033, Japan.
†
Financial support was in part provided by ACTꢀC from JST,
GrantꢀinꢀAid for Scientific Research on Innovative Areas from MEXT
and the Naito foundation. Electronic Supplementary Information (ESI)
available: [experimental details, including procedures, characterization of
new products, 1H and 13C NMR charts,]. See DOI: 10.1039/c000000x/
1
Reviews: (a) T. Satoh and M. Miura, Chem. Eur. J., 2010, 16, 11212;
(b) F. W. Patureau, J. WencelꢀDelord and F. Glorius, Aldrichimica
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Synth. Catal., 2014, 356, 1443.
14 A part of results in this manuscript was presented in the 2nd
International Conference on Organometallics and Catalysis (Nara),
on Oct. 27, 2014.
2
Review on the firstꢀrow transition metalꢀcatalyzed CꢀH bond
activation/CꢀC bond formation, (a) A. A. Kulkarni and O. Daugulis,
Synthesis, 2009, 4087; (b) N. Yoshikai, Synlett, 2011, 1047; (c) L.
Ackermann, J. Org. Chem., 2014, 79, 8948.
15 T. Shioiri, K. Ninomiya and S. Yamada, J. Am. Chem. Soc., 1972, 94
6203.
,
16 We assume that the observed large difference in the reactivity of 1c
and 1d can be ascribed to the purity of the Cp*Co(III)ꢀcomplexes.
Synthesis and purification of the dimeric iodide complex 1c was
easy, while the synthetic procedure as well as purification of the
dimeric chloride complex 1d was difficult.
3
4
T. Yoshino, H. Ikemoto, S. Matsunaga and M. Kanai, Angew. Chem.
Int. Ed., 2013, 52, 2207.
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Matsunaga and M. Kanai, J. Am. Chem. Soc., 2014, 136, 5424.
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17 For detailed procedure, see Electronic Supplementary Information.
See also, S. A. Frith and J. Spencer in: Inorganic Syntheses:
Reagents for Transition Metal Complex and Organometallic
Syntheses, Vol. 28, (Ed.: R. J. Angelici), Inorganic Syntheses, Inc.,
pp 273–277.
5
18 Results of unsuccessful substrates: 3ꢀMeꢀN-(pyrimidinꢀ2ꢀyl) indole
2o gave product 4oa in only 7% yield. Indole bearing a dimethyl
carbamoyl group afforded trace, if any, product. 2ꢀPhenylpyridine
6
7
8
B. Sun, T. Yoshino, S. Matsunaga and M. Kanai, Adv. Synth. Catal.,
2014, 356, 1491.
and
NꢀMeꢀbenzamide, which are suitable substrates under Cp*Irꢀ
W. W. Metcalf and W. A. van der Donk, Annu. Rev. Biochem., 2009,
78, 65.
catalysis,12 did not afford products under Cp*Coꢀcatalysis.
19 S. H. Park, J. Kwak, K. Shin, J. Ryu, Y. Park and S. Chang, J. Am.
Chem. Soc., 2014, 136, 2492.
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Ackermann, Chem. Rev., 2011, 111, 1315 and references therein.
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Graphical Abstracts:
[Cp*CoI2]2
(5 mol %)
AgSbF6
O
O
X
NP(OAr)2
H
X
+
N3 P(OAr)2
(20 mol %)
N
N
N
N
cationic Co(III) catalysis
N
N
graphical
abstracts:
C2ꢀselective
indole
CꢀH
phosphoramidation under Cp*Co(III) catalysis was achieved.
4 | J. Name., 2012, 00, 1-3
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