Rhodium(III)-Catalyzed C-H Olefination of Aromatic/Vinyl Acids with Unactivated Olefins at Room Temperature

Article abstract of DOI:10.1021/acs.orglett.0c01636

A Rh(III)-catalyzed COOH-assisted C-H alkenylation of aromatic acids with unactivated alkenes at room temperature is described. Further, the highly challenging β-C-H olefination of acrylic acids with unactivated olefins was also demonstrated. In these reactions, ortho-alkenylated aromatic/vinylic acids were prepared in good to excellent yields. A possible reaction mechanism involving ortho C-H activation and a five-membered rhodacycle formation was proposed and supported by the deuterium-labeling studies and isolation of a key rhodacycle intermediate.

Full text of DOI:10.1021/acs.orglett.0c01636

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Letter
Rhodium(III)-Catalyzed C−H Olefination of Aromatic/Vinyl Acids
with Unactivated Olefins at Room Temperature
Subramanian Jambu and Masilamani Jeganmohan*
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ABSTRACT: A Rh(III)-catalyzed COOH-assisted C−H alkeny-
lation of aromatic acids with unactivated alkenes at room
temperature is described. Further, the highly challenging β-C−H
olefination of acrylic acids with unactivated olefins was also
demonstrated. In these reactions, ortho-alkenylated aromatic/
vinylic acids were prepared in good to excellent yields. A possible
reaction mechanism involving ortho C−H activation and a five-
membered rhodacycle formation was proposed and supported by
the deuterium-labeling studies and isolation of a key rhodacycle
intermediate.
he transition-metal-catalyzed chelation-assisted C−H
reactivity as well as the unbiased nature of unactivated alkenes.
Recently, by employing bis chelating group such as 8-
aminoquninoline, alkenylation was done with unactivated
olefins (eq 2).7 However, this type of transformation with a
monodentate ligand was not well explored.8 Herein, we report
an unprecedented Rh(III)-catalyzed C−H olefination of
aromatic/vinyl carboxylic acids with unactivated olefins at
room temperature (eq 3). The reaction provides ortho-
alkenylated aromatic acids and β-C−H-olefinated acrylic
acids. In the reaction, the COOH group was not involved in
the intramolecular cyclization with an alkene.5j
Treatment of 2-methoxybenzoic acid (1a) with vinyl-
cyclohexene (2a, 4.0 equiv) in the presence of
[{RhCl2(Cp*)}2] (5 mol %), Ag2O (50 mol %), and
Na2HPO4 (1.0 equiv) in DMF at room temperature for 24 h
afforded ortho-vinylated benzoic acid 3aa in 76% yield
(Scheme 1). The olefination reaction was examined with
oxidants such as AgOAc, Ag2CO3, Ag2O, Cu(OAc)2·H2O,
Cu(OAc)2, CuO, K2S2O8, and (NH4)2S2O8. Among the tested
T
functionalization of organic molecules via a deprotona-
tion pathway has emerged as a powerful synthetic tool in
organic synthesis.1 Several chemical bonds are constructed
efficiently in a highly step-economical manner by using this
method.2 A recent observation clearly showed that the C−H
activation via a deprotonation pathway can be performed at
room temperature.3 However, in practical terms, most of the
known transformations required a higher reaction temperature.
Substituted alkenes are versatile synthetic intermediates and
have found widespread application in various organic trans-
formations.4−7 The metal-catalyzed C−H olefination of
substituted aromatics with alkenes is a highly effective method
to synthesize arylated alkenes in a stereoselective manner
(Figure 1).4 For this kind of transformation, only activated
olefins such as enones, acrylates, acrylonitriles, acrylamides,
vinylsulfones, and styrenes are efficiently used (eq 1).5,6 The
C−H olefination with unactivated olefins is very challenging
and not well explored in the literature due to the lower
Scheme 1. Ortho-Vinylation of 2-Methoxybenzoic Acid
Received: May 13, 2020
Figure 1. Known C−H alkenylation reaction.
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oxidants, Ag2O was very successful, providing product 3aa in
76% yield. AgOAc and Ag2CO3 were partially effectual, giving
3aa in 48% and 57% yields, respectively. Other oxidants were
not effective. Further, the ortho-alkenylation reaction was
studied with various bases such as carbonates, acetates,
phosphates, and amines. Among them, phosphate base
(Na2HPO4) was effective, affording 3aa in 76% yield. Other
bases were partially effective or ineffective. The reaction was
tested with 2.0 equiv of Na2HPO4. In the reaction, product 3aa
was formed in 76% yield. The olefination reaction was
examined with solvents such as DMSO, toluene, cyclohexane,
CH3CN, THF, 1,4-dioxane, DME, MeOH, TFE, 1,2-DCE, 1,2-
dichlorobenzene, and acetic acid instead of DMF. CH3CN,
THF, MeOH, and TFE were less efficient for the reaction,
giving 3aa in 20−30% yields. Remaining solvents were
ineffective.
minor amounts ortho-allylated products were also observed.
Interestingly, in the case of 2,5-dimethoxybenzoic acid (1i),
exclusively ortho-allylated benzoic acid 3ia was formed in 75%
yield. 4-Methoxybenzoic acid (1j) and 4-fluorobenzoic acid
(1k) reacted with 2a to give products 3ja and 3ka in 35% and
57% yields, respectively. Interestingly, thiophene-2-carboxylic
acid (1l) was also efficiently involved in the reaction, giving
product 3la in 55% yield.
The vinylation reaction was further examined with
substituted benzoic acids 1m−s. The alkenylation reaction is
highly regioselective, and the vinylation selectively takes place
at the less hindered side. The reaction of 3-methoxy- (1m), 3-
methyl- (1n), and 3-bromobenzoic acids (1o) with 2a afforded
ortho-olefinated products 3ma, 3na, and 3oa in 57%, 75%, and
55% yields, respectively. Gratifyingly, the strong electron-
withdrawing 3-NO2 benzoic acid (1p) was also involved in the
reaction, furnishing product 3pa in 43% yield with an 8:1 E/Z
ratio. In these reactions, alkenylation selectively takes place at
the less hindered C6 position. 3,4-Dimethoxy (1q) and 3,4-
dimethylbenzoic acids (1r) reacted with 2a to afford ortho-
olefinated products 3qa and 3ra in 72% and 77% yields,
respectively. In the reaction, the C−H activation takes place at
the C6 position of aromatic acids. Similarly, 2-naphthoic acid
(1s) reacted with 2a to give product 3sa in 62% yield. In the
reaction, vinylation takes place at the C3 position.
The alkenylation reaction was tested with substituted
aromatic acids 1b−s (Scheme 2). The reaction of 2-
Scheme 2. Scope of Aromatic and Heteroaromatic Acids
The olefination reaction was examined with unactivated α-
substituted olefins (4.0 equiv) (Scheme 3). In the reaction,
Scheme 3. Scope of Unactivated Aliphatic Alkenes
methylbenzoic acid (1b) with 2a delivered ortho-alkenylated
benzoic acid 3ba in 75% yield. Halogen substituents such as F,
Cl, and Br at the ortho-position of benzoic acids 1c−e reacted
with 2a to yield ortho-vinylated benzoic acids 3ca−3ea in 71%,
62%, and 73% yields, respectively. In the case of 2-Cl and Br
benzoic acids, mixtures of ortho-alkenylated/allylated products
were observed in ratios of 6:1 and 5:1, respectively. The
reaction of 2-phenylbenzoic acid (1f) with 2a gave ortho-
alkenylated aromatic acid 3fa in 52% yield. The reaction of
disubstituted benzoic acids such as 2,3-dimethoxy- (1g) and
2,4-dimethoxybenzoic acids (1h) with 2a yielded products 3ga
and 3ha in 82% and 68% yields, respectively. In 1g and 1h,
mixtures of branched vinylated as well as linear allylated or
vinylated products were observed. These α-substituted olefins
are substantial starting materials for the preparation of
synthetic fatty acids, synthetic lubricants, polymers, and
plasticizers. The reactions of 1-hexene (2b), 1-octene (2c),
and 1-decene (2d) with 1g afforded the corresponding
vinylated products 4gb, 4gc, and 4gd in 85%, 69%, and 58%
yields, respectively. In the reaction, linear type allylated
B
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product 5 was observed in a minor amount. It is important to
note that as the length of carbon chain of α-olefin increases the
selectivity of branched vinylated product increases. In 1-hexene
(2b), 1-octene (2c), and 1-decene (2d), branched/linear
alkenes were observed in 4:1, 6:1, and 7:1 ratios. The position
of the substituent on the aromatic acid also plays a crucial role
for the control of selectivity of branched vs linear alkenes. In
the reaction of 2,5-dimethoxybenzoic acid (1i), linear ortho-
allylated benzoic acid 5ib was observed in 73% yield with high
selectivity. 3,3-Dimethylbut-1-ene (2e) reacted with 1g at 80
°C for 24 h to give exclusively ortho-vinylated benzoic acid 3ge
in 67% yield. The structure of product 3ge was confirmed by
single-crystal X-ray crystallography (CCDC 1990502). Sim-
ilarly, 4-methoxybenzoic acid (1j) with 2e at 80 °C for 24 h
gave the expected product 3je in 34% yield. In addition,
dialkenylation product 3je′ was also observed in 29% yield in
the reaction. Allylbenzene (2f) reacted with 1g to afford ortho-
allylated benzoic acid 5gf in 87% yield along with a minor
amount of branched alkene in a 15:1 ratio.
or 1n to provide olefinated products 3al and 3nm in 45% and
58% yields, respectively. In the reaction, a minor amount of
branched alkene product was observed.
In addition, a highly challenging β-C−H olefination of
substituted acrylic acids with unactivated alkenes was also
examined (Scheme 5). The reaction of α-methyl acrylic acid
Scheme 5. Scope of Acrylic Acids with Unactivated
Alkenens
Subsequently, the olefination reaction was tested with
functional group substituted unactivated olefins (Scheme 4).
Scheme 4. Scope of Functionalized Unactivated Alkenes
(6a) with vinylcyclohexene (2a) under similar reaction
conditions provided trans-diene derivative 6aa in 63% yield
in a highly stereoselective manner. Similarly, 1-hexene (2b), 1-
octene (2c), and 1-decene (2d) reacted with 6a to give
expected diene derivatives 6ab−ad in moderate 31%, 45%, and
22% yields, respectively, with 4:1 to 5:1 E/Z ratios. When α-
methyl acrylic acid (6a) was treated with 2f, the corresponding
olefinated products 6af + 6af′ were observed in 53% yield with
a 7:1 ratio. An α-substituted acrylic acid such as (2-(4-
methoxyphenyl)acrylic acid (6b) efficiently reacted with 2a to
deliver β-C−H olefinated product 6ga in 69% yield with a 3:1
E/Z ratio. The reaction was not compatible with acrylic acid
and β-methyl- and phenyl-substituted acrylic acids.
To understand the reaction mechanism, the following
mechanistic studies were carried out (Scheme 6). Treatment
of 1j with CD3COOD under the optimized reaction conditions
provided D-1j in 96% yield with 37% deuterium incorporation
at both ortho carbons. Further, the reaction of 1j with 2a
afforded ortho-olefinated product D-3ja in 32% yield with 20%
deuterium incorporation at the ortho-carbon of benzoic acid.
This result clearly explains that the ortho C−H bond activation
is a reversible process. Later, a rhodacycle intermediate 7a was
isolated in 52% yield in the reaction of 1r with a stoichiometric
amount of [Cp*RhCl2]2, KHCO3, and DMSO in MeOH
solvent under air at 60 °C for 1 h. Later, a rhodacycle
intermediate 7a was treated with 2a, giving ortho-olefination
product 3ja in 75% yield. This result clearly reveals that the
five-membered rhodacycle intermediate is formed in the
reaction. Finally, the intermolecular competitive experiment
between 1j and 1k with 2a was carried out. In the reaction,
products 3ja and 3ka were observed in 33% and 30% yields,
respectively. This result suggests that the electronic effect of
benzoic acids has no apparent impact on the reaction and it
proceeds via an acetate-assisted deprotonation pathway.
To account for the present alkenylation reaction, a plausible
reaction mechanism is proposed in Scheme 7. The reaction of
aromatic acid 1 with [Cp*RhCl2]2 in the presence of Ag2O and
Hydroxy group substituted alkenes such as pent-4-en-1-ol
(2g), hex-5-en-1-ol (2h), and dec-9-en-1-ol (2i) reacted with
1g to furnish branched as well as allylated products 4gg, 4gh,
and 4gi in 66%, 70%, and 85% yields, respectively. Similarly, 4-
methoxybenzoic acid (1j) reacted with 2i to provide branched
as well as allylated products 4ji in 40% yield. Further, ester-,
amine-, and ether-substituted unactivated olefins (2 equiv)
were examined. The reaction of ester-functionalized alkene 2j
with 1a provided exclusively vinylated product 3aj in 38% yield
in a highly regioselective manner. Heterocyclic functionalized
alkenes such as saccharine 2k react with 1a or 1g to afford
olefinated products 3ak and 3gk in 55% and 62% yields,
respectively. In the reaction, a minor amount of branched
alkene was also observed. Furthermore, unactivated alkenes
containing a coumarin 2l or estrone 2m group reacted with 1a
C
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Rh−C bond of intermediate C with the β-carbon of an alkene
2. Intermediate G undergoes base-prompted dehydrometala-
tion to give intermediate F and a branched-type vinylated
product 5.7e Later, the rhodium(I) complex F was oxidized
into active Rh(III) species A in the presence of Ag2O and
RCOOH. A similar type of base-assisted proto-demetalation is
involved in the formation of linear-type vinylated product
formation 3. For a typical β-hydride elimination, the syn
coplanarity arrangement of metal with Cβ-H is needed. The
rotation to achieve syn coplanarity in intermediate G is
restricted due to the cyclic system. In this case, Na2HPO4 or
Ag2O could deprotonate the benzylic proton of intermediate H
(eq 4). It is important to note the possibility that typical β-
hydride elimination in eq 4 for the formation of product 5
from intermediate G cannot be completely excluded. In OH
group substituted alkenes 2g−i, linear as well as branched
products were observed equally. It is assumed that the OH
group coordinates with a metal in intermediates D and G to
provide linear as well as branched products.
Scheme 6. Mechanistic Studies
In conclusion, we have described an unprecedented C−H
alkenylation of commercially available aromatic/vinylic acids
with unactivated olefins in the presence of a rhodium(III)
complex at room temperature. The olefination reaction has
broad substrate scope, and various substituted aromatic acids
as well as functionalized unactivated alkenes were compatible
for the reaction. A convincing reaction mechanism is proposed
and supported by deuterium-labeling studies and isolation of a
five-membered rhodacycle intermediate.
Scheme 7. Proposed Mechanism
ASSOCIATED CONTENT
* Supporting Information
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The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01636.
General experimental procedures and characterization
details, 1H NMR and 13C NMR spectra of all
compounds, single-crystal X-ray diffraction data for
compound 3ge (PDF)
Accession Codes
CCDC 1990502 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
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Na2HPO4 afforded complex A. Complex A reacts with benzoic
acid 1 to provide a five-membered rhodacycle intermediate B
via a carboxylate-assisted deprotonation pathway. Then the
replacement of RCOOH by unactivated olefin 2a forms
intermediate C. Coordinative 1,2-migratory insertion (less
hindered side) of an alkene bond into the Rh−carbon bond of
intermediate C gives a rhodacycle intermediate D. Then
intermediate D undergoes β-hydride elimination at the freely
rotatable CH2 side to form intermediate E. Later, intermediate
E undergoes reductive elimination to give a Rh(I) complex F
and ortho-allylated benzoic acid 4. Later, the active Rh(III)
species A is regenerated in the reaction of a rhodium(I)
complex F with Ag2O and RCOOH. Intermediate G is crucial
for the formation of branched type vinylated product 5.
Intermediate G is formed by the coordinative insertion of the
Masilamani Jeganmohan − Department of Chemistry, Indian
Institute of Technology Madras, Chennai 600036, Tamil Nadu,
India; orcid.org/0000-0002-7835-3928;
Email: mjeganmohan@iitm.ac.in
Author
Subramanian Jambu − Department of Chemistry, Indian
Institute of Technology Madras, Chennai 600036, Tamil
Nadu, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01636
Notes
The authors declare no competing financial interest.
D
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Letter
(4) (a) Le Bras, J.; Muzart, J. Intermolecular Dehydrogenative Heck
Reactions. Chem. Rev. 2011, 111, 1170. (b) Yeung, C. S.; Dong, Vy.
M. Catalytic Dehydrogenative Cross-Coupling: Forming Carbon−
Carbon Bonds by Oxidizing Two Carbon−Hydrogen Bonds. Chem.
Rev. 2011, 111, 1215. (c) Manikandan, R.; Jeganmohan, M. Recent
Advances in the Ruthenium(II)-Catalyzed Chelation-Assisted C−H
Olefination of Substituted Aromatics, Alkenes and Heteroaromatics
with Alkenes via the Deprotonation Pathway. Chem. Commun. 2017,
53, 8931−8947. See also references cited therein. (d) Leow, D.; Li,
G.; Mei, T.-S.; Yu, J.-Q. Activation of remote meta-C-H bonds
assisted by an end-on template. Nature 2012, 486, 518−522. (e) Bera,
M.; Maji, A.; Sahoo, S. K.; Maiti, D. Palladium(II)-Catalyzed meta-C-
H Olefination: Constructing Multisubstituted Arenes through Homo-
Diolefination and Sequential Hetero-Diolefination. Angew. Chem., Int.
Ed. 2015, 54, 8515−8519. (f) Ma, W.; Gandeepan, P.; Li, J.;
Ackermann, L. Recent advances in positional-selective alkenylations:
removable guidance for twofold C−H activation. Org. Chem. Front.
2017, 4, 1435−1467. (g) Gandeepan, P.; Cheng, C.-H. Allylic
Carbon−Carbon Double Bond Directed Pd-Catalyzed Oxidative
ortho-Olefination of Arenes. J. Am. Chem. Soc. 2012, 134, 5738−5741.
(h) Reddy, M. C.; Jeganmohan, M. Total Synthesis of Aristolactam
Alkaloids via Synergistic C-H Bond Activation and Dehydro-Diels-
Alder Reactions. Chem. Sci. 2017, 8, 4130−4135.
(5) (a) Rakshit, S.; Grohmann, C.; Besset, T.; Glorius, F. Rh(III)-
Catalyzed Directed C−H Olefination Using an Oxidizing Directing
Group: Mild, Efficient, and Versatile. J. Am. Chem. Soc. 2011, 133,
2350−2353. (b) Wang, F.; Song, G.; Li, X. Rh(III)-Catalyzed
Tandem Oxidative Olefination−Michael Reactions between Aryl
Carboxamides and Alkenes. Org. Lett. 2010, 12, 5430−5433.
(c) Zhou, J.; Li, B.; Hu, F.; Shi, B.-F. Rhodium(III)-Catalyzed
Oxidative Olefination of Pyridines and Quinolines: Multigram-Scale
Synthesis of Naphthyridinones. Org. Lett. 2013, 15, 3460−3463.
(d) Yadav, M. R.; Rit, R. K.; Shankar, M.; Sahoo, A. K. Sulfoximine-
Directed Ruthenium-Catalyzed ortho-C−H Alkenylation of (Hetero)-
Arenes: Synthesis of EP3 Receptor Antagonist Analogue. J. Org. Chem.
2014, 79, 6123−6134. (e) Liang, Q.-J.; Jiang, B.; Xu, Y.-H.; Loh, T.-P.
Palladium-Catalyzed Regioselective Olefination of O-Acetyl Cyano-
hydrins. J. Org. Chem. 2018, 83, 8265−8271. (f) Padala, K.;
Jeganmohan, M. Ruthenium-Catalyzed Ortho-Alkenylation of Ar-
omatic Ketones with Alkenes by C−H Bond Activation. Org. Lett.
2011, 13, 6144−6147. (g) Trita, A. S.; Biafora, A.; Drapeau, M. P.;
Weber, P.; Gooßen, L. J. Regiospecific ortho-C−H Allylation of
Benzoic Acids. Angew. Chem., Int. Ed. 2018, 57, 14580−14584.
(h) Reddy, M. C.; Jeganmohan, M. Ruthenium-catalyzed ortho
alkenylation of aromatic nitriles with activated alkenes via C-H bond
activation. Chem. Commun. 2015, 51, 10738−10741. (i) Trita, A. S.;
Biafora, A.; Pichette-Drapeau, M.; Weber, P.; Goossen, L. J.
Regiospecific ortho-C−H Allylation of Benzoic Acids. Angew. Chem.,
Int. Ed. 2018, 57, 14580. (j) Jambu, S.; Tamizmani, M.; Jeganmohan,
M. Ruthenium(II)-Catalyzed Cyclization of Aromatic Acids with
Allylic Acetates via Redox-Free Two-Fold Aromatic/Allylic C−H
Activations: Combined Experimental and DFT Studies. Org. Lett.
2018, 20, 1982−1986.
ACKNOWLEDGMENTS
■
We thank the DST-SERB (CRG/2018/000606), India, for the
support of this research. S.J. thanks IITM for an HTRA
Fellowship.
REFERENCES
■
(1) Reviews: (a) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H.
Ruthenium(II)-Catalyzed C−H Bond Activation and Functionaliza-
tion. Chem. Rev. 2012, 112, 5879−5918. (b) Wencel-Delord, J.;
Droge, T.; Liu, F.; Glorius, F. Towards mild metal-catalyzed C−H
bond activation. Chem. Soc. Rev. 2011, 40, 4740−4761. (c) Kuhl, N.;
Schroder, N.; Glorius, F. Formal SN-Type Reactions in Rhodium(III)-
Catalyzed C-H Bond Activation. Adv. Synth. Catal. 2014, 356, 1443−
1460. (d) Lyons, M. T.; Sanford, M. S. Palladium-Catalyzed Ligand-
Directed C−H Functionalization Reactions. Chem. Rev. 2010, 110,
1147−1169. (e) Colby, D. A.; Bergman, R. G.; Ellman, J. A.
Rhodium-Catalyzed C−C Bond Formation via Heteroatom-Directed
C−H Bond Activation. Chem. Rev. 2010, 110, 624−655. (f) Engle, K.
M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Weak Coordination as a Powerful
Means for Developing Broadly Useful C−H Functionalization
Reactions. Acc. Chem. Res. 2012, 45, 788−802. (g) Daugulis, O.;
Do, H.-Q.; Shabashov, D. Palladium- and Copper-Catalyzed Arylation
of Carbon−Hydrogen Bonds. Acc. Chem. Res. 2009, 42, 1074−1086.
(h) Gandeepan, P.; Cheng, C.-H. Transition-Metal-Catalyzed π-
Bond-Assisted C-H Bond Functionalization: An Emerging Trend in
Organic Synthesis. Chem. - Asian J. 2015, 10, 824−838.
(2) Reviews: (a) Leitch, J. A.; Frost, C. G. Ruthenium-Catalysed σ-
Activation for Remote meta-Selective C−H Functionalization. Chem.
Soc. Rev. 2017, 46, 7145−7153. (b) Zhao, Q.; Meng, G.; Nolan, S.-P.;
Szostak, M. N-Heterocyclic Carbene Complexes in C−H Activation
Reactions. Chem. Rev. 2020, 120 (4), 1981−2048. See also references
cited therein. (c) Nareddy, P.; Jordan, F.; Szostak, M. Highly
Chemoselective Ruthenium(II)-Catalyzed Direct Arylation of Cyclic
and N,N-dialkylbenzamides with Aryl Silanes. Chem. Sci. 2017, 8,
3204−3210. (d) Hartwig, J. F. Evolution of C−H Bond
Functionalization from Methane to Methodology. J. Am. Chem. Soc.
2016, 138 (1), 2−24. (e) Yang, Y.; Lan, J.; You, J. Oxidative C−H/
C−H Coupling Reactions between Two (Hetero)arenes. Chem. Rev.
2017, 117, 8787−8863. (f) Sambiagio, C.; Schonbauer, D.; Blieck, R.;
Dao-Huy, T.; Pototschnig, G.; Schaaf, P.; Wiesinger, T.; Zia, M. F.;
Wencel-Delord, J.; Besset, T.; Maes, B. U. W.; Schnurch, M. A
comprehensive overview of directing groups applied in metal-
catalysed C−H functionalisation chemistry. Chem. Soc. Rev. 2018,
47, 6603−6743. (g) Davies, D. L.; Macgregor, S. A.; McMullin, C. L.
Computational Studies of Carboxylate-Assisted C−H Activation and
Functionalization at Group 8−10 Transition Metal Centers. Chem.
Rev. 2017, 117, 8649−8709. (h) Leitch, J. A.; Frost, C. G. Ruthenium-
catalysed σ-activation for remote meta-selective C−H functionalisa-
tion. Chem. Soc. Rev. 2017, 46, 7145−7153. (i) Mishra, N. K.; Sharma,
S.; Park, J.; Han, S.; Kim, I. S. Recent Advances in Catalytic C(sp2)−
H Allylation Reactions. ACS Catal. 2017, 7, 2821−2847.
(3) (a) Ferrer Flegeau, E.; Bruneau, C.; Dixneuf, P. H.; Jutand, A.
Autocatalysis for C-H Bond Activation by Ruthenium(II) Complexes
in Catalytic Arylation of Functional Arenes. J. Am. Chem. Soc. 2011,
133, 10161−10170. (b) Gensch, T.; Hopkinson, M. N.; Glorius, F.;
Wencel-Delord, J. Mild metal-catalyzed C−H activation: examples
and concepts. Chem. Soc. Rev. 2016, 45, 2900−2936. See also
references cited therein. (c) Manikandan, R.; Madasamy, P.;
Jeganmohan, M. Ruthenium-Catalyzed Oxidant-Free Allylation of
Aromatic Ketoximes with Allylic Acetates at Room Temperature.
Chem. - Eur. J. 2015, 21, 13934−13938. (d) Manikandan, R.;
Madasamy, P.; Jeganmohan, M. Ruthenium-Catalyzed ortho
Alkenylation of Aromatics with Alkenes at Room Temperature with
Hydrogen Evolution. ACS Catal. 2016, 6, 230−234. (e) Yang, W.;
Sun, J.; Xu, X.; Zhang, Q.; Liu, Q. Hydroxyamination of aryl C−H
bonds with N-hydroxycarbamate by synergistic Rh/Cu catalysis at
room temperature. Chem. Commun. 2014, 50, 4420−4422.
(6) (a) Arockiam, P. B.; Fischmeister, C.; Bruneau, C.; Dixneuf, P.
H. Ruthenium diacetate-catalysed oxidative alkenylation of C−H
bonds in air: synthesis of alkenyl N-arylpyrazoles. Green Chem. 2011,
13, 3075−3078. (b) Mehta, V. P.; Lopez, J-A-G.; Greaney, M. F.
Ruthenium-Catalyzed Cascade C-H Functionalization of Phenyl-
acetophenones. Angew. Chem., Int. Ed. 2014, 53, 1529−1533.
(c) Lanke, V.; Prabhu, K. R. Highly Regioselective C2-Alkenylation
of Indoles Using the N-Benzoyl Directing Group: An Efficient Ru-
Catalyzed Coupling Reaction. Org. Lett. 2013, 15, 2818−2821.
(d) Yang, J.; Seto, Y. W.; Yoshikai, N. Cobalt-Catalyzed
Intermolecular Hydroacylation of Olefins through Chelation-Assisted
Imidoyl C−H Activation. ACS Catal. 2015, 5, 3054−3057. (e) Jambu,
S.; Sivasakthikumaran, R.; Jeganmohan, M. Aerobic Oxidative
Alkenylation of Weak O-Coordinating Arylacetamides with Alkenes
via a Rh(III)-Catalyzed C−H Activation. Org. Lett. 2019, 21, 1320−
1324. (f) Kozhushkov, S.-I.; Ackermann, L. Ruthenium-catalyzed
E
https://dx.doi.org/10.1021/acs.orglett.0c01636
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
direct oxidative alkenylation of arenes through twofold C−H bond
functionalization. Chem. Sci. 2013, 4, 886−896. (g) Parthasarathy, K.;
Bolm, C. Rhodium(III)-Catalyzed Selective ortho-Olefinations of N-
Acyl and N-Aroyl Sulfoximines by C-H Bond Activation. Chem. - Eur.
J. 2014, 20, 4896−−4900. (h) Kommagalla, Y.; Mullapudi, V. B.;
Francis, F.; Ramana, C. V. Ruthenium(II)-catalyzed switchable C3-
alkylation versus alkenylation with acrylates of 2-pyridylbenzofurans
via C−H bond activation. Catal. Sci. Technol. 2015, 5, 114−117.
(i) Ackermann, L.; Pospech, J. Ruthenium-Catalyzed Oxidative C−H
Bond Alkenylations in Water: Expedient Synthesis of Annulated
Lactones. Org. Lett. 2011, 13, 4153. (j) Gao, K.; Yoshikai, N. Cobalt−
Phenanthroline Catalysts for the ortho Alkylation of Aromatic Imines
under Mild Reaction Conditions. Angew. Chem., Int. Ed. 2011, 50,
6888−6892. (k) Chinnagolla, R. K.; Jeganmohan, M. Regioselective
Synthesis of Isocoumarins by Ruthenium-Catalyzed Aerobic Oxida-
tive Cyclization of Aromatic Acids with Alkynes. Chem. Commun.
2012, 48, 2030−2032.
(7) (a) Deb, A.; Bag, S.; Kancherla, R.; Maiti, D. Palladium-
Catalyzed Aryl C−H Olefination with Unactivated, Aliphatic Alkenes.
J. Am. Chem. Soc. 2014, 136, 13602−13605. (b) Deb, A.; Hazra, A.;
Peng, Q.; Paton, R. S.; Maiti, D. Detailed Mechanistic Studies on
Palladium-Catalyzed Selective C−H Olefination with Aliphatic
Alkenes: A Significant Influence of Proton Shuttling. J. Am. Chem.
Soc. 2017, 139, 763−775. (c) Maity, S.; Kancherla, R.; Dhawa, U.;
Hoque, E.; Pimparkar, S.; Maiti, D. Switch to Allylic Selectivity in
Cobalt-Catalyzed Dehydrogenative Heck Reactions with Unbiased
Aliphatic Olefins. ACS Catal. 2016, 6, 5493−5499. (d) Yamaguchi,
T.; Kommagalla, Y.; Aihara, Y.; Chatani, N. Cobalt-catalyzed
chelation assisted C−H allylation of aromatic amides with unactivated
olefins. Chem. Commun. 2016, 52, 10129−10132. (e) Manoharan, R.;
Sivakumar, G.; Jeganmohan, M. Cobalt-catalyzed C−H olefination of
aromatics with unactivated alkenes. Chem. Commun. 2016, 52,
10533−10536. (f) Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed,
Aminoquinoline-Directed Coupling of sp2 C−H Bonds with Alkenes.
Org. Lett. 2014, 16 (17), 4684−4687. (g) Ueura, K.; Satoh, T.; Miura,
M. An Efficient Waste-Free Oxidative Coupling via Regioselective C-
H Bond Cleavage: Rh/Cu-Catalyzed Reaction of Benzoic Acids with
Alkynes and Acrylates under Air. Org. Lett. 2007, 9 (7), 1407−1409.
(h) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. Rhodium-Catalyzed
Regioselective Olefination Directed by a Carboxylic Group. J. Org.
Chem. 2011, 76, 3024−3033. Review: (i) Satoh, T.; Miura, M.
Oxidative Coupling of Aromatic Substrates with Alkynes and Alkenes
under Rhodium Catalysis. Chem. - Eur. J. 2010, 16, 11212−11222.
(8) (a) Lu, M.-Z.; Chen, X.-R.; Xu, H.; Dai, H.-X.; Yu, J.-Q. Ligand-
enabled ortho-C−H olefination of phenylacetic amides with
unactivated alkenes. Chem. Sci. 2018, 9, 1311−1316. (b) Tsai, A.
S.; Brasse, M.; Bergman, R. G.; Ellman, J. Rh(III)-Catalyzed Oxidative
Coupling of Unactivated Alkenes via C-H Activation. Org. Lett. 2011,
13, 540−542. (c) Takahama, Y.; Shibata, Y.; Tanaka, K. Oxidative
Olefination of Anilides with Unactivated Alkenes Catalyzed by an
(Electron-Deficient η5- Cyclopentadienyl)Rhodium(III) Complex
Under Ambient Conditions. Chem. - Eur. J. 2015, 21, 9053−9056.
(d) Xue, X.; Xu, J.; Zhang, L.; Xu, C.; Pan, Y.; Xu, L.; Li, H.; Zhang,
W. Rhodium(III)-Catalyzed Direct C-H Olefination of Arenes with
Aliphatic Olefins. Adv. Synth. Catal. 2016, 358, 573−583. Review:
(e) Deb, A.; Maiti, D. Emergence of Unactivated Olefins for the
Synthesis of Olefinated Arenes. Eur. J. Org. Chem. 2017, 2017, 1239−
1252.
F
https://dx.doi.org/10.1021/acs.orglett.0c01636
Org. Lett. XXXX, XXX, XXX−XXX