Angewandte
Communications
Chemie
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C H Activation
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Rhodium-Catalyzed meta-C H Functionalization of Arenes
Milan Bera+, Soumitra Agasti+, Rajdip Chowdhury, Rahul Mondal, Debasis Pal, and
Debabrata Maiti*
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Abstract: Rhodium-catalyzed ortho-C H functionalization is
well known in the literature. Described herein is the Xphos-
selectivity. Indeed, ortho-selective functionalization of arene
[6]
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C H bonds have been successfully explored with rhodium.
Nevertheless, development of selective distal arene meta-C
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supported rhodium catalysis of meta-C H olefination of
benzylsulfonic acid and phenyl acetic acid frameworks with
the assistance of a para-methoxy-substituted cyano phenol as
the directing group. Complete mono-selectivity is observed for
both scaffolds. A wide range of olefins and functional groups
attached to arene are tolerated in this protocol.
H functionalizations by rhodium catalysis remain challenging.
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Herein, we disclose a rhodium-catalyzed meta-C H olefina-
tion of benzylsulfonyl and phenyl acetic acid scaffolds using
a nitrile-based template (Scheme 1).
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D
irecting-group-assisted functionalization of unreactive C
H bonds has been a vibrant research area in synthetic organic
chemistry during the past two decades. This process delivers
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the selective C H functionalization products in a step- and
atom-economical fashion. Several transition metals can
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effectively catalyze selective C H functionalization reactions
with the assistance of directing groups (DGs).[1] In all these
cases, DGs have been identified as the crucial component for
Scheme 1. Overview of present work.
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ortho-C H activation and predictable transformation relies
on formation of either a five or six membered metallacycle
intermediate. In stark contrast, only a limited number of
methods are available for selective meta-functionalization of
arenes.[2] A directing-group-based approach for selective
The initial reaction of 2-cyanophenol-derived benzylsul-
fonyl ester 1 (for structure see Scheme2) with ethyl acrylate in
the presence of 5 mol% of [{Rh(COD)Cl}2], 10 mol% of Ac-
Gly-OH as a ligand, and Ag2CO3 as an oxidant was
unsuccessful. However, a trace amount of the desired product
was observed when the reaction was performed with CuCl2 as
the oxidant in 1,2-dichloroethane (DCE) as the solvent.
Furthermore, a systematic study of temperature dependence
and solvent indicated that 1208C and DCE increased the yield
up to 12%. Next, modified the DG by introducing an
electron-donating group, such as methoxy, at the para position
to the cyano substituent. Such electron donation through the
aromatic ring to the cyano substituent is expected to enhance
the mode of rhodium–nitrile linear coordination. To our
delight, a slightly higher yield of the olefination product
(17%) with complete mono-selectivity was observed. In
addition, a wide variety of oxidants was tested and copper
trifluoroacetate was found to be best (46%).[7] Use of V2O5 as
a co-oxidant further improved the yield to 51%. We have
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remote meta-C H functionalizations has been pioneered by
the group of Yu[3] and subsequently extended by the groups of
Tan and Li, as well as our group.[4] In these cases, a nitrile-
containing template assists the palladium center to activate
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remote meta-C H bonds (ꢀ 10 bonds away) of a tethered
arene by formation of a cyclophane-like pre-transition state
through linear end-on coordination of the nitrile to metal
center.[3,4]
Analogous to the PdII/Pd0 pathways, the RhIII/RhI cycles
are commonly present in oxidative coupling reactions. In
addition, a few similar aspects have been observed for both
palladium- and rhodium-catalyzed oxidative coupling reac-
tions:[5] 1) C H activation is well known for C(sp ) H bonds,
2
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2) formation of M C bonds by C H activation are generated
through chelation assistance, 3) scope with respect to the
coupling partners is limited to unsaturated molecules such as
alkenes and alkynes. However, rhodium-catalyzed oxidative
C H functionalizations have been less explored in contrast to
palladium-catalyzed reactions. Rhodium catalysis would be
highly desirable if it can provide better reaction scope and
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subsequently tested this meta-C H olefination reaction with
other rhodium salts. Rhodium(II) salts such as [Rh2(OAc)4]
and [{Rh(TFA)2}2] were completely inactive, however
rhodium(III) salts such as [{Rh(Cp*)Cl2}2] provided the
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desired meta-C H olefination in comparable yield and
selectivity.[7] Another catalytic condition was developed by
further optimization of the reaction with [{Rh(COD)Cl}2],
CuCl2 as oxidant, and trifluoroacetic acid (TFA) as an
additive (60%; 49% mono and 11% di). A number of
mono- and bidentate phosphine ligands were evaluated for
both reaction protocols (Scheme 2). After studying various
ligands, we found the Rh/XPhos[8] combination to be most
promising as it provided the mono-olefinated product in 69%
(reaction conditions A) and 72% (reaction conditions B)
[*] Dr. M. Bera,[+] S. Agasti,[+] R. Chowdhury, R. Mondal, D. Pal,
Prof. D. Maiti
Department of Chemistry, Indian Institute of Technology Bombay
Powai, Mumbai-400076 (India)
E-mail: dmaiti@chem.iitb.ac.in
[+] These authors contributed equally to this work.
Supporting information for this article can be found under:
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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