Cp?Rh(iii) and Cp?Ir(iii)-catalysed redox-neutral C-H arylation with quinone diazides: quick and facile synthesis of arylated phenols

Article abstract of DOI:10.1039/c5cc03187g

Cp?Rh(iii)- and Cp?Ir(iii)-catalysed direct C-H arylation with quinone diazides as efficient coupling partners is disclosed. This redox-neutral protocol offers a facile, operationally simple and environmentally benign access to arylated phenols. The reaction represents the first example of Cp?Ir(iii)-catalysed C-H direct arylation reaction.

Full text of DOI:10.1039/c5cc03187g

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DOI: 10.1039/C5CC03187G
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Cp*Rh(III) and Cp*Ir(III)-Catalysed Redox-Neutral C-H
Arylation with Quinone Diazides: Quick and Facile Synthesis
of Arylated Phenols
Cite this: DOI: 10.1039/x0xx00000x
Shang-Shi Zhang,‡ Chun-Yong Jiang,‡ Jia-Qiang Wu, Xu-Ge Liu, Qingjiang Li, Zhi-
Shu Huang, Ding Li,* Honggen Wang*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
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chemical entities. Current C–H arylation reactions are seldom
compatible with the phenol functionality due to the oxidative and/or
harsh conditions used.
Cp*Rh(III) and Cp*Ir(III)-catalysed direct C–H arylation
with quinone diazides as efficient coupling partners is
disclosed. This redox-neutral protocol offers
a facile,
Our hypothesis was inspired by the recent success of employing
diazo compounds as coupling partners in Cp*Rh(III)-catalyzed C–H
functionalizations (Scheme 1c).[14] Structurally, quinone diazides can
be regarded as carbonyl diazo compounds bearing two electron-
acceptors.[15,16] Therefore, a Rh-carbenoid was expected to be
formed after the C–H activation event. Thereafter, by a subsequent
-insertion and rearomatization, a direct C–H arylation reaction
should be achieved (vide infra for a proposal of mechanism).
operationally simple and environmentally benign access to
arylated phenols. The reaction represents the first example of
Cp*Ir(III)-catalysed C–H direct arylation reaction.
The biaryl scaffold is prevalent in numerous functional
molecules. Conventionally, the transition metal-catalysed cross
coupling reaction provides a reliable strategy for biaryl synthesis.[1]
Recently, with the advent and great advances of metal-catalyzed C–
H
activation reaction,[2] direct C–H arylation offers a more
straightforward and atom-economic pathway for their synthesis.[3]
Cp*Rh(III) are among the most attractive catalysts which enable the
functionalization of various C–H bonds to furnish diverse C–C and
C–heteroatom bonds under typically mild reaction conditions and
with low catalyst loading.[4] In the context of C–H arylation reaction,
however, only limited examples exist (Scheme 1a).[5-10] For instance,
it has been demonstrated that Cp*Rh(III) could promote the
dehydrogenative coupling of two distinct arenes in an
intramolecular[5] or intermolecular[6] manner via dual C–H activation.
Though elegant, these reactions usually occur under drastic reaction
conditions. And for intermolecular reactions, a large excess of one
arene is typically needed. In addition, several examples of oxidative
C-H coupling reactions with aryl organometallic reagents, namely
arylboronic acids[7] and arylsilanes[8] were reported, with large
amount of oxidants Ag+ and/or Cu2+ salt necessitated. Interestingly,
it is only very recently that aryl iodides are identified as efficient
coupling partners for Rh(III)-catalyzed arylation of anilides.[9] Aside
from these examples, Li realized an alternative C–H arylation
reaction via an interesting formal Michael addition/rearomatization
pathways by using 4-hydroxycyclohexa-2,5-dienones as the
arylating reagents (Scheme 1b).[10] Herein, we report our realization
of a mild Cp*Rh(III) and Cp*Ir(III)-catalyzed C–H arylation with
quinone diazides to furnish arylated phenols[11] under simple and
redox-neutral reaction conditions. To the best of our knowledge, this
is the first example of employing Cp*Ir(III) as catalyst for C–H
arylation reaction.[12,13] It should be noted that phenols are useful
Scheme 1. Rh(III)-catalyzed biaryl synthesis via C–H functionalization.
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Importantly, quinone diazides are readily synthesized by the withdrawing CF3 retarded the reaction, giving 5ca’ in only 28%
diazotization of aminophenols, or by the functionalization of anilines yield.
or phenols.[17]
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DOI: 10.1039/C5CC03187G
Initially, we examined the reaction of 2-phenylpyridine 1a with
quinone diazide 2a. Delightedly, we were able to quickly identify
that the reaction proceeded smoothly in the presence of [Cp*RhCl2]2
(2.5 mol %), AgSbF6 (20 mol%) and PivOH (10 mol %) in DCM at
o
50 C, giving the desired arylation product 3aa in 73% yield, along
with 17% diarylation product 3aa’ (eq 1). Interestingly, the switch of
the catalyst to [Cp*IrCl2]2 produced the diarylation product 3aa’
predominately. By increasing the loading of quinone diazide 2a to
2.5 equivalents, 3aa’ could be obtained in a high yield of 80% (eq 2).
The scope of this transformation was investigated. It was found
that the reaction was robust to tolerate various functional groups,
giving the corresponding products in generally good to excellent
yields (Scheme 2). For para-substituted arenes, significant amounts
of diarylation products were usually observed (3aa-3da, 3la, 4ca,
5aa-5ca). However, the meta-substituents could assure a single
monoarylation reaction, with the reaction occurring at the less
sterically congested positions (3ea-3ga, 4da, 5ea). Notably, ortho-
substituents did not hamper the reactivity (3ha, 3ia, 5da). The
Scheme 2. Cp*Rh(III)-catalysed C–H arylation of different arenes with
substituent effect on the pyridine ring was also examined. To our
quinone diazide 2a. [a] monoarylation: diarylation ratio.
delight, a number of substituents regardless of the electronic
properties were well tolerated (3ja-3na). We would like to point out
that 6-methoxypyridin-2-yl (3ja) and 3-methylpyridin-2-yl (3na),
which are potentially difficult directing groups due to the steric
hindrance, effected the reaction smoothly. 2-(Naphthalen-2-
yl)pyridine was arylated exclusively at the -position in 86% yield
(3oa). Benzo[h]quinolone was also a suitable substrate (3pa). Apart
from pyridinyl, pyrazolyl (4ca, 4da) and pyrimidyl (5aa-5fa) groups
were also effective chelating groups for this transformation.
We then investigated the substrate scope of quinone diazides
(Scheme 3). With 2-(m-tolyl)pyrimidine as substrate, we were
delighted to find that the reaction was compatible not only with
para-quinone diazides (5ea-5ed), but also with ortho-quinone
diazides (5ee-5eh). Thus, a variety of quinone diazides with different
substituents proceeded smoothly, giving the arylation products in
moderate to good yields. The survival of halides like Cl and Br
provided opportunities for further functionalization.
Scheme 3. Cp*Rh(III)-catalysed C–H arylation with various quinone
Due to the important utility of extended -conjugated
compounds in materials, we further evaluated the substrate scope for
the formation of bis-functionalization products (Scheme 4). Again,
different substrates bearing a N-heterocyclic directing group such as
pyridinyl, pyrazolyl and pyrimidyl underwent reaction without
difficulties. Notably, the hydroxymethyl group was also tolerated,
suggesting the mildness of this reaction (4ba’). It should be noted
the biheteroaryl 1-(thiophen-3-yl)-1H-pyrazole also delivered the
diarylation products in excellent yield (4fa’). The electron-
diazides.
To further expand the scope of this reaction, we turned our
attention to the arylation of indoles and pyroles (Scheme 5). Indoles
and pyroles frequently occur in biologically active compounds. By
installing a pyrimidyl directing group, the reaction of 1-(pyrimidin-
2-yl)-1H-indole with 2a worked effectively in the presence of either
Cp*Rh(III) or Cp*Ir(III) catalyst, with Cp*Ir(III) giving slightly
higher yield (6aa). The reaction efficiency was thus evaluated under
the catalysis of Cp*Ir(III). Delightedly, various indoles bearing
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different substituents at different positions were suitable substrates
for this transformation. Of note, the -methyl substituted indole also
delivered the arylation product in moderate yield (6ia).
Unfortunately, the biheterocyclic 1H-pyrrolo[2,3-c]pyridine showed
no reactivity in this reaction (6ja). Importantly, pyroles were also
suitable substrates for this transformation, although the 2-formyl
pyrole substrate gave a yield of only 27% (7ba).
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DOI: 10.1039/C5CC03187G
On the basis of these experiments and literature precedents, a
proposed mechanism was outlined in scheme 6. The active
Cp*Rh(III) or Cp*Ir(III) catalyst is generated by ligand exchange
with PivOH. C–H activation under the assistance of N-containing
hetercyclic directing group delivers a cyclometallated intermediate A.
According to our KIE experiments, this step promoted by
Cp*Rh(III) catalyst is not involved in the rate-determining step. A
reacts with quinone diazide to form a metal carbene species B with
the extrusion of N2. The subsequent migratory insertion furnishes
intermediate C. Upon protonation with PivOH, D was produced and
the catalyst is regenerated. The aromatization of intermediate D
gives the final arylated product.
Scheme 4. Cp*Ir(III)-catalysed C–H diarylation reaction with 2a.
Scheme 6. Mechanistic proposal.
In summary, we developed a novel C–H arylation reaction by
using quinone diazides as coupling partners. The reaction was
efficiently catalysed by Cp*Rh(III) or Cp*Ir(III) catalysts, offering a
quick and facile access to arylated phenols. Broad substrate scope
and good functional group tolerance were observed. To the best of
our knowledge, this reaction represents the first example of
Cp*Ir(III)-catalysed direct C–H arylation reaction.
Scheme 5. Cp*Ir(III)-catalysed C–H arylation of indoles and pyroles. [a]
Cp*Rh(III) was used instead of Cp*Ir(III).
Acknowledgements
We are grateful for the support of this work by a Start-up Grant from
Sun Yat-sen University and National Natural Science Foundation of
China (81402794 and 21472250).
The exposure of 4-chlorobenzenediazonium chloride to the
reaction led to no desired arylation product, indicating the
importance of the quinone moiety for this reaction (eq 3). A kinetic
isotope effect value of 1.1 was observed, which suggests the C–H
activation is not involved in the rate-determining step (eq 4).[18]
Notes and references
S.-S. Zhang,‡ C.-Y. Jiang,‡, J.-Q. Wu, X.-G. Liu, Dr. Q. Li, Prof. Dr. Z.-S.
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DOI: 10.1039/C5CC03187G
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