Rhodium-Catalyzed C-H/C-H Cross Coupling of Benzylthioethers or Benzylamines with Thiophenes Enabled by Flexible Directing Groups

Article abstract of DOI:10.1021/acs.orglett.9b01679

Reported herein is an efficient synthetic protocol to ortho-functionalized 2-aryl thiophenes via Rh(III)-catalyzed C-H/C-H cross coupling of benzylthioethers or benzylamines with thiophenes. Both ortho- and meta-substituted benzylthioethers give monoheteroarylated products, while ortho-unhindered substrates mainly provide diheteroarylated benzylthioethers. The C-H/C-H cross coupling of benzylamines with thiophenes exclusively generates diheteroarylated benzaldehydes. Mechanistic investigation discloses a three-step tandem process involving the ortho-C-H diheteroarylation of benzylamine, the oxidation of benzylamine to imine, and the hydrolysis of imine to aldehyde.

Full text of DOI:10.1021/acs.orglett.9b01679

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Rhodium-Catalyzed C−H/C−H Cross Coupling of Benzylthioethers or
Benzylamines with Thiophenes Enabled by Flexible Directing
Groups
Shiping Yang, Rui Cheng, Tingxing Zhao, Anping Luo, Jingbo Lan,* and Jingsong You*
Key Laboratory of Green Chemistry and Technology of Ministry of Education, College of Chemistry, Sichuan University, 29
Wangjiang Road, Chengdu 610064, P.R. China
S
* Supporting Information
ABSTRACT: Reported herein is an efficient synthetic
protocol to ortho-functionalized 2-aryl thiophenes via Rh-
(III)-catalyzed C−H/C−H cross coupling of benzylthioethers
or benzylamines with thiophenes. Both ortho- and meta-
substituted benzylthioethers give monoheteroarylated prod-
ucts, while ortho-unhindered substrates mainly provide diheteroarylated benzylthioethers. The C−H/C−H cross coupling of
benzylamines with thiophenes exclusively generates diheteroarylated benzaldehydes. Mechanistic investigation discloses a three-
step tandem process involving the ortho-C−H diheteroarylation of benzylamine, the oxidation of benzylamine to imine, and the
hydrolysis of imine to aldehyde.
ryl thiophene scaffolds, especially for ortho-functionalized
2-aryl thiophenes, are important structural motifs in
directing groups on aromatic rings to achieve C−H/C−H
cross-coupling reaction with heteroarenes.6
A
organic functional materials, pharmaceuticals, natural products,
Thioethers are an important class of functional groups,
which is widely found in a variety of natural products and
bioactive compounds.7 Utilizing thioether as a directing group
in the field of ortho-selective direct C−H functionalization of
arenes has drawn much attention owing to the easy
transformation from the thioether group to various other
functional groups.8 Moreover, thioether-directed selective C−
H bond functionalization reaction provides a straightforward
route for the preparation of useful sulfur-containing com-
pounds in pharmaceuticals and materials science.8a,c,d,9
However, to our knowledge, the use of flexible chain-
containing thioethers, such as benzylthioether, as the directing
group to accomplish the oxidative C−H/C−H cross coupling
with heteroarenes, remains still unsolved perhaps because of
the sulfur’s ability to poison many transition-metal catalysts
and the weak directing ability of the flexible directing
group.8b,10,11 Herein, Rh-catalyzed oxidative C−H/C−H
cross couplings of benzylthioethers with thiophenes have
been developed to rapidly construct a variety of ortho-
functionalized 2-aryl thiophenes.
Initially, the cross coupling between (3-methylbenzyl)(p-
tolyl)thioether (1a) and benzo[b]thiophene (2a) was
employed for the optimization of reaction conditions (Table
S1). When utilizing the [RhCp*Cl2]2/AgSbF6 catalyst system,
the desired product 2-(4-methyl-2-(p-tolylthiomethyl)phenyl)-
benzo[b] thiophene (3a) was obtained in 45% yield (Table S1,
entry 1). In the absence of [RhCp*Cl2]2, the cross-coupled
product 3a was not observed (Table S1, entry 2). No AgSbF6
would also result in a dramatically diminished yield (Table S1,
and synthetic intermediates (Figure 1).1,2 For example, 2-((2-
Figure 1. Selected examples of ortho-functionalized aryl-thiophene
derivatives.
(benzothiophen-2-yl)benzyl)sulfinyl)acetamide is a promising
wake-promoting agent, which displays superior activity
compared with commercially available 2-((diphenylmethyl)-
sulfinyl)acetamide (Modafinil).2d The current sythetic routes
to these aryl−heteroaryl scaffolds typically suffer from limits
such as selective ortho-halogenation, borylation, or other
prefunctionalization, as well as probably inevitable protection
and deprotection of functional groups.2,3 Recently, the C−H/
C−X cross coupling of heteroarenes with aryl halides has
emerged as a facile and efficient pathway to aryl−heteroaryl
structures.4 However, from the viewpoint of the accessibility of
coupling partners and the atom- and step-economy of coupling
reaction, transition-metal-catalyzed C−H/C−H cross coupling
of two (hetero)aromatic substrates through a chelation-assisted
strategy is doubtless a more ideal approach to prepare these
bi(hetero)aryl derivatives.5 Through this strategy, almost all of
the common functional groups, such as amino, hydroxyl,
carboxyl, the carbonyl of ketones and aldehydes, and various
nitrogen-containing heterocycles, have been developed as
Received: May 13, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01679
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
entry 3). Among oxidants investigated, Ag2O was proved to be
the best choice, while Cu(OAc)2, AgOAc, and Ag2CO3 led to
trace amounts of 3a or no desired product (Table S1, entries
6−8). Optimization of additives showed that PivOH was a
much better option than acetic acid (HOAc), 1-adamantane-
carboxylic acid (AdCOOH), trifluoroacetic acid (TFA),
trifluoromethanesulfonic acid (TfOH), mesitylenecarboxylic
acid (MesCOOH), and cesium acetate (CsOAc) (Table S2).
Lowering the reaction temperature from 140 to 100 °C made
no difference to the yield of 3a (Table S3, entries 6 and 7).
Optimization of solvents showed that CH2Cl2 was the best
choice in most of the common organic solvents, providing 3a
in 72% yield (Table S3, entries 1−12). In addition, when the
reaction time was shortened from 24 to 18 h or the reaction
temperature was lowered from 100 to 80 °C, the yield of 3a
apparently decreased (Table S3, entries 15 and 16).
in moderate yields. Methyl(3-methylbenzyl)thioether was also
proved to be a suitable substrate, providing 3m in 62% yield.
The substrate scope of benzothiophenes and thiophenes was
also investigated (Scheme 2). Benzothiophenes substituted by
b
Scheme 2. Scope of Thiophenes
Subsequently, the scope of benzylthioethers was investigated
under the optimal conditions (Scheme 1). It was found that a
b
Scheme 1. Scope of Benzylthioethers
a
b
1a (1.0 mmol), 2g (3.0 mmol) in CH2Cl2 (5.0 mL). Reaction
conditions: 1 (0.2 mmol), 2 (0.6 mmol) in CH2Cl2 (1.0 mL). Isolated
yield.
chloro and bromo could undergo this reaction in good yields
(4a−c). Especially, 3-bromobenzo[b]thiophene with steric
hindrance could react with 1a, affording the cross-coupled
product 4b in 80% yield. Thiophenes with various functional
groups such as methyl, phenyl, chloro, bromo, and acyl groups
could be well tolerated in this cross-coupling reaction (4d−j).
Gratefully, bis(3-methylbenzyl)thioether could also undergo
diheteroarylation to give the corresponding product 4k. It is
worthy to note that various monobromo- and dibromo-
substituted thiophene substrates can be tolerated under the
standard conditions, which provide opportunities for further
synthetic transformations (4b−c, 4g−h, and 4k).
a
b
36 h. Reaction conditions: 1 (0.2 mmol), 2a (0.6 mmol) in CH2Cl2
(1.0 mL). Isolated yield.
ortho-Heteroaryl benzaldehydes are important structure
motifs in the field of organic synthesis and material science
(Figure 1).2b,c,e,f Surprisingly, under the same reaction
conditions and lowering the reaction temperature to 80 °C,
the C−H/C−H cross coupling of benzylamines with
thiophenes could occur smoothly, affording diheteroarylated
benzaldehydes as the final products (Scheme 3). A variety of
N-methylbenzylamine derivatives with various functional
groups were compatible with this protocol (6b−f). Note-
worthily, the meta-substituted benzylamine gave the diheter-
oarylated product successfully (6g), and the monoheteroary-
lated product was not observed. For ortho-substituted
benzylamine substrates, both mono- and diheteroarylated
products were not detected, perhaps because the presence of
steric hindrance inhibited the coordination of amino with the
Rh(III) core and subsequent ortho-C−H activation. Delight-
edly, the cross coupling of various substituted thiophenes with
variety of benzylthioether derivatives could smoothly react
with 2a, affording the 2-aryl benzothiophenes (3a−g) in
moderate to good yields. This catalytic system was compatible
with various functional groups, such as methyl, chloro, bromo,
ester, and phenyl groups. (Naphthalen-2-ylmethyl)(p-tolyl)-
thioether selectively gave the heteroarylated product at the C3
position of the naphthalene ring (3h). Benzyl(p-tolyl)thioether
(1i) mainly generated diheteroarylated product 3i. Only trace
monoheteroarylated product was detected, and the unreacted
1i remained unchanged by thin-layer chromatography (TLC)
detection. The corresponding oxidized byproduct for 1i was
not observed. The yield of 3i was not improved when
prolonging the reaction time from 24 to 36 h. Under standard
conditions, para-methyl-, fluoro-, and bromo-substituted
substrates afforded diheteroarylated benzylthioethers (3j−l)
B
DOI: 10.1021/acs.orglett.9b01679
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. C−H/C−H Cross Coupling of Benzylamines
a
with Heteroarenes
Based on the above mechanism study, a possible pathway for
both kinds of cross-coupling reactions is depicted in Scheme
4.8c,13 First, the coordination of Cp*Rh(III) with 1 or 5 and
Scheme 4. Proposed Mechanism
a
Reaction conditions: 5 (0.2 mmol), 2 (0.6 mmol) in CH2Cl2 (1.0
mL). Isolated yield.
N-methylbenzylamines delivered the desired products in
synthetically useful yields (6h−k). Notably, caffeine, a popular
psychoactive substance, could also undergo ortho-selective C−
H/C−H cross coupling with benzylamine, giving 2,6-bis-
(caffein-8-yl)benzaldehyde (6l) in 50% yield.
To clarify the mechanism of the cross-coupling reaction of
1a with 2a, hydrogen/deuterium exchange experiments and
kinetic isotope effect (KIE) experiments were carried out. In
either the presence or the absence of 1a, 2a reacted with D2O
(20.0 equiv) for 2.5 h under the standard conditions, and an
H/D exchange ratio of 11% was observed [eqs S3 and S4].
These results indicate that the C2−H metalation of 2a may be
a reversible process, which excludes the possibility of a Heck-
like mechanism, because the C−H functionalization of
thiophenes through a Heck-type mechanism usually does not
involve a C−H activation pathway.12 Subsequently, the parallel
reactions between 1a and 2a as well as [D]-1a and 2a were
performed. A KIE value of 1.63 (kH/kD) was observed [eqs 1,
S6, and S7]. However, the parallel reactions between 1a and 2a
as well as 1a and [D]-2a provided a KIE value of 3.10 (kH/kD)
[eqs 2, S8, and S9]. These results imply that the C2−H bond
cleavage of 2a may be the rate-determining step of this cross-
coupling reaction, while the ortho-C−H cleavage of 1a is
probably not involved in the rate-determining step. Next, to
figure out the mechanism of the formation of diheteroarylated
benzaldehydes, the C−H/C−H cross coupling of benzalde-
hyde (7) with 2a was investigated. Under the optimal reaction
conditions, treatment of 7 with 2a afforded only a trace
amount of 6a [eq 3]. Moreover, in the absence of 2a,
treatment of N-methylbenzylamine (5a) did not lead to 7
under the standard conditions [eq 4]. These results indicate
that the C−H/C−H cross coupling of benzylamines with
heteroarenes is not initiated from the oxidation of amines to
aldehydes.
the subsequent occurrence of aryl ortho-C−H bond activation
generate the rhodacycle intermediate I. I reacts with 2a to
afford the key bi(hetero)aryl rhodium intermediate II. Then, a
reductive elimination occurs, providing the cross-coupled
product 3 and Cp*Rh(I). Cp*Rh(I) is reoxidized by Ag(I)
to Cp*Rh(III) to start on the next catalytic cycle. When N-
methylbenzylamine (5a) is used as the coupling partner,
intermediate II undergoes a reductive elimination to generate
Rh(I) intermediate III. Rh(I) intermediate III is oxidized to
the Rh(III) intermediate and subsequent ortho-C−H bond
activation to afford IV. IV encounters a catalytic recycle again
to introduce the second heteroaryl, affording intermediate V,
followed by the oxidation of benzylamine to imine by Ag2O,
forming imine intermediate VI. The hydrolysis of VI provides
the desired product 6a. The intermediates I, III, IV, V, and VI
of the cross coupling of 2a with 5a were confirmed by MALDI-
TOF-MS.
To further demonstrate the usefulness of our methodology,
the transformation of thioether was carried out.8d,14 By
regulating the loading of m-chloroperbenzoic acid (m-
CPBA), the coupled product 3a could be oxidized to deliver
the sulfoxide 8 and sulfone 9 in good yields, respectively [eq
5].
C
DOI: 10.1021/acs.orglett.9b01679
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(2) (a) Wang, W.; Xu, J.; Lai, Y.-H.; Wang, F. Alternating Aromatic
and Transannular Chromophores with and without Linker: Effect of
Transannular π-π Interaction on the Optical Property of Dithiapar-
acyclophane-based Copolymers. Macromolecules 2004, 37, 3546−
3553. (b) Pietrangelo, A.; MacLachlan, M. J.; Wolf, M. O.; Patrick, B.
O. Synthesis and Structures of Novel Luminescent Bent Acenedi-
thiophenes. Org. Lett. 2007, 9, 3571−3573. (c) Boschelli, D. H.; Wu,
B.; Sosa, A. C. B.; Chen, J.; Asselin, M.; Cole, D. C.; Lee, J.; Yang, X.;
Chaudhary, D. Synthesis and PKCθ Inhibitory Activity of a Series of
4-(Indol-5-ylamino)thieno[2,3-b]pyridine-5-carbonitriles. Bioorg.
Med. Chem. Lett. 2008, 18, 2850−2853. (d) Lesur, B.; Lin, Y. G.;
Marcy, V. R.; Aimone, L. D.; Gruner, J.; Bacon, E. R.; Chatterjee, S.
Aryl-Heteroaryl Derivatives as Novel Wake-Promoting Agents. Chem.
Biol. Drug Des. 2013, 81, 429−432. (e) Hassanpour, A.; De Carufel,
C. A.; Bourgault, S.; Forgione, P. Synthesis of 2,5-Diaryl-Substituted
Thiophenes as Helical Mimetics: Towards the Modulation of Islet
Amyloid Polypeptide (IAPP) Amyloid Fibril Formation and
Cytotoxicity. Chem. - Eur. J. 2014, 20, 2522−2528. (f) Feng, S.;
Zhang, C.; Liu, Y.; Bi, Z.; Zhang, Z.; Xu, X.; Ma, W.; Bo, Z. Fused-
Ring Acceptors with Asymmetric Side Chains for High-Performance
Thick-Film Organic Solar Cells. Adv. Mater. 2017, 29, 1703527.
(3) (a) Lu, F.; Sun, H.; Du, A.; Feng, L.; Li, X. Selective Alkylation
and Arylation of C−F Bond with Grignard Reagents. Org. Lett. 2014,
16, 772−775. (b) Hu, F.; Szostak, M. Ruthenium(0)-Catalyzed C−H
Arylation of Aromatic Imines under Neutral Conditions: Access to
Biaryl Aldehydes. Org. Lett. 2016, 18, 4186−4189.
In summary, a highly efficient synthetic strategy to ortho-
functionalized 2-aryl thiophenes has been developed via
Rh(III)-catalyzed C−H/C−H cross coupling of thiophenes
with benzylthioethers or benzylamines. Both ortho- and meta-
substituted benzylthioethers generate monoheteroarylated
products, while ortho-unhindered substrates mainly provide
the diheteroarylated benzylthioethers. Under similar con-
ditions, the cross coupling of benzylamines with thiophenes
can also occur smoothly, exclusively affording diheteroarylated
benzaldehydes as the final products, and the monoheteroary-
lated product is not observed. It is worthy to note that our
protocol can tolerate various monobromo- and dibromo-
substituted thiophene substrates, affording the cross-coupled
products in moderate to good yields, which offers oppor-
tunities for further modification of products through the
transition-metal-catalyzed various coupling reactions of
(hetero)aryl bromides.
(4) For selected reviews, see: (a) Alberico, D.; Scott, M. E.; Lautens,
M. Aryl−Aryl Bond Formation by Transition-Metal-Catalyzed Direct
Arylation. Chem. Rev. 2007, 107, 174−238. (b) McGlacken, G. P.;
Bateman, L. M. Recent Advances in Aryl−Aryl Bond Formation by
Direct Arylation. Chem. Soc. Rev. 2009, 38, 2447−2464. (c) Acker-
mann, L.; Vicente, R.; Kapdi, A. R. Transition-Metal-Catalyzed Direct
Arylation of (Hetero)Arenes by C−H Bond Cleavage. Angew. Chem.,
Int. Ed. 2009, 48, 9792−9826.
(5) For selected reviews, see: (a) Zhang, M.; Zhang, Y.; Jie, X.;
Zhao, H.; Li, G.; Su, W. Recent Advances in Directed C−H
Functionalizations Using Monodentate Nitrogen-Based Directing
Groups. Org. Chem. Front. 2014, 1, 843−895. (b) Chen, Z.; Wang,
B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Transition Metal-Catalyzed
C−H Bond Functionalizations by the Use of Diverse Directing
Groups. Org. Chem. Front. 2015, 2, 1107−1295. (c) Huang, H.; Ji, X.;
Wu, W.; Jiang, H. Transition Metal-Catalyzed C−H Functionalization
of N-Oxyenamine Internal Oxidants. Chem. Soc. Rev. 2015, 44, 1155−
1171. (d) Liu, C.; Yuan, J.; Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A.
Oxidative Coupling between Two Hydrocarbons: An Update of
Recent C−H Functionalizations. Chem. Rev. 2015, 115, 12138−
12204. (e) Yang, Y.; Lan, J.; You, J. Oxidative C−H/C−H Coupling
Reactions between Two (Hetero)arenes. Chem. Rev. 2017, 117,
8787−8863.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01679.
■
S
1
Experimental details, characterization, and copies of H
and 13C NMR spectra of product (PDF)
Accession Codes
CCDC 1908988 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 Authors
■
*E-mail: jingbolan@scu.edu.cn.
*E-mail: jsyou@scu.edu.cn.
(6) For selected examples, see: (a) Wencel-Delord, J.; Nimphius, C.;
Wang, H.; Glorius, F. Rhodium(III) and HexabromobenzeneA
Catalyst System for the Cross-Dehydrogenative Coupling of Simple
Arenes and Heterocycles with Arenes Bearing Directing Groups.
Angew. Chem., Int. Ed. 2012, 51, 13001−13005. (b) Zhang, Y.; Zhao,
H.; Zhang, M.; Su, W. Carboxylic Acids as Traceless Directing Groups
for the Rhodium(III)-Catalyzed Decarboxylative C−H Arylation of
Thiophenes. Angew. Chem., Int. Ed. 2015, 54, 3817−3821. (c) Qin, X.;
Li, X.; Huang, Q.; Liu, H.; Wu, D.; Guo, Q.; Lan, J.; Wang, R.; You, J.
Rhodium(III)-Catalyzed ortho C−H Heteroarylation of (Hetero)-
aromatic Carboxylic Acids: A Rapid and Concise Access to π-
Conjugated Poly-heterocycles. Angew. Chem., Int. Ed. 2015, 54, 7167−
7170. (d) Li, B.; Lan, J.; Wu, D.; You, J. Rhodium(III)-Catalyzed
ortho-Heteroarylation of Phenols through Internal Oxidative C−H
Activation: Rapid Screening of Single-Molecular White-Light-
Emitting Materials. Angew. Chem., Int. Ed. 2015, 54, 14008−14012.
(e) Gao, D.-W.; Gu, Q.; You, S.-L. An Enantioselective Oxidative C−
H/C−H Cross-Coupling Reaction: Highly Efficient Method to
Prepare Planar Chiral Ferrocenes. J. Am. Chem. Soc. 2016, 138,
2544−2547.
ORCID
Jingbo Lan: 0000-0001-5937-0987
Jingsong You: 0000-0002-0493-2388
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this work by the National NSF of China
(Nos. 21871193, 21672154, and 21432005) is gratefully
appreciated. The authors also thank the Comprehensive
Training Platform Specialized Laboratory, College of Chem-
istry, Sichuan University.
REFERENCES
■
(1) Takimiya, K.; Shinamura, S.; Osaka, I.; Miyazaki, E.
Thienoacene-Based Organic Semiconductors. Adv. Mater. 2011, 23,
4347−4370.
D
DOI: 10.1021/acs.orglett.9b01679
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(7) (a) Nugent, R. A.; Schlachter, S. T.; Murphy, M. J.; Cleek, G. J.;
Poel, T. J.; Wishka, D. G.; Graber, D. R.; Yagi, Y.; Keiser, B. J.;
Olmsted, R. A.; Kopta, L. A.; Swaney, S. M.; Poppe, S. M.; Morris, J.;
Tarpley, W. G.; Thomas, R. C. Pyrimidine Thioethers: A Novel Class
of HIV-1 Reverse Transcriptase Inhibitors with Activity Against
BHAP-Resistant HIV. J. Med. Chem. 1998, 41, 3793−3803.
(b) Greger, H.; Pacher, T.; Vajrodaya, S.; Bacher, M.; Hofer, O.
Infraspecific Variation of Sulfur-Containing Bisamides from Aglaia
Leptantha. J. Nat. Prod. 2000, 63, 616−620. (c) Wheelhouse, R. T.;
Jennings, S. A.; Phillips, V. A.; Pletsas, D.; Murphy, P. M.; Garbett, N.
C.; Chaires, J. B.; Jenkins, T. C. Design, Synthesis, and Evaluation of
Novel Biarylpyrimidines: A New Class of Ligand for Unusual Nucleic
Acid Structures. J. Med. Chem. 2006, 49, 5187−5198. (d) Nakazawa,
T.; Xu, J.; Nishikawa, T.; Oda, T.; Fujita, A.; Ukai, K.; Mangindaan, R.
E. P.; Rotinsulu, H.; Kobayashi, H.; Namikoshi, M. Lissoclibadins 4−
7, Polysulfur Aromatic Alkaloids from the Indonesian Ascidian
Lissoclinum cf. Badium. J. Nat. Prod. 2007, 70, 439−442. (e) Ilardi, E.
A.; Vitaku, E.; Njardarson, J. T. Data-Mining for Sulfur and Fluorine:
An Evaluation of Pharmaceuticals to Reveal Opportunities for Drug
Design and Discovery. J. Med. Chem. 2014, 57, 2832−2842.
(14) Kawashima, H.; Yanagi, T.; Wu, C.-C.; Nogi, K.; Yorimitsu, H.
Regioselective C−H Sulfanylation of Aryl Sulfoxides by Means of
Pummerer-Type Activation. Org. Lett. 2017, 19, 4552−4555.
(8) (a) Yu, M.; Xie, Y.; Xie, C.; Zhang, Y. Palladium-Catalyzed C−H
Alkenylation of Arenes Using Thioethers as Directing Groups. Org.
Lett. 2012, 14, 2164−2167. (b) Zhang, X.-S.; Zhu, Q.-L.; Zhang, Y.-
F.; Li, Y.-B.; Shi, Z.-J. Controllable Mono-/Dialkenylation of Benzyl
Thioethers through Rh-Catalyzed Aryl C−H Activation. Chem. - Eur.
J. 2013, 19, 11898−11903. (c) Zhang, X.-S.; Zhang, Y.-F.; Li, Z.-W.;
Luo, F.-X.; Shi, Z.-J. Synthesis of Dibenzo[c,e]oxepin-5(7H)-ones
from Benzyl Thioethers and Carboxylic Acids: Rhodium-Catalyzed
Double C−H Activation Controlled by Different Directing Groups.
Angew. Chem., Int. Ed. 2015, 54, 5478−5482. (d) Wang, B.; Lin, C.;
Liu, Y.; Fan, Z.; Liu, Z.; Zhang, Y. Thioether-Directed Acetoxylation
of C(sp2)−H Bonds of Arenes by Palladium Catalysis. Org. Chem.
Front. 2015, 2, 973−977. (e) Liu, L.; Wang, G.; Jiao, J.; Li, P. Sulfur-
Directed Ligand-Free C−H Borylation by Iridium Catalysis. Org. Lett.
2017, 19, 6132−6135.
(9) Moon, S.; Nishii, Y.; Miura, M. Thioether-Directed Peri-Selective
C−H Arylation under Rhodium Catalysis: Synthesis of Arene-Fused
Thioxanthenes. Org. Lett. 2019, 21, 233−236.
(10) (a) Murray, S. G.; Hartley, F. R. Coordination Chemistry of
Thioethers, Selenoethers, and Telluroethers in Transition-metal
Complexes. Chem. Rev. 1981, 81, 365−414. (b) Barbero, N.;
Martin, R. Ligand-Free Ni-Catalyzed Reductive Cleavage of Inert
Carbon-Sulfur Bonds. Org. Lett. 2012, 14, 796−799.
(11) (a) Lu, Y.; Wang, D.-H.; Engle, K. M.; Yu, J.-Q. Pd(II)-
Catalyzed Hydroxyl-Directed C−H Olefination Enabled by Monop-
rotected Amino Acid Ligands. J. Am. Chem. Soc. 2010, 132, 5916−
5921. (b) Wang, X.; Lu, Y.; Dai, H.-X.; Yu, J.-Q. Pd(II)-Catalyzed
Hydroxyl-Directed C−H Activation/C−O Cyclization: Expedient
Construction of Dihydrobenzofurans. J. Am. Chem. Soc. 2010, 132,
12203−12205. (c) Lu, Y.; Leow, D.; Wang, X.; Engle, K. M.; Yu, J.-Q.
Hydroxyl-Directed C−H Carbonylation Enabled by Mono-N-
Protected Amino Acid Ligands: An Expedient Route to 1-
Isochromanones. Chem. Sci. 2011, 2, 967−971. (d) Li, G.; Leow,
D.; Wan, L.; Yu, J.-Q. Ether-Directed ortho-C−H Olefination with a
Palladium(II)/Monoprotected Amino Acid Catalyst. Angew. Chem.,
Int. Ed. 2013, 52, 1245−1247.
(12) (a) Ueda, K.; Yanagisawa, S.; Yamaguchi, J.; Itami, K. A
General Catalyst for the β-Selective C−H Bond Arylation of
Thiophenes with Iodoarenes. Angew. Chem., Int. Ed. 2010, 49,
́
́
8946−8949. (b) Colletto, C.; Islam, S.; Julia-Hernandez, F.; Larrosa,
I. Room-Temperature Direct β-Arylation of Thiophenes and
Benzo[b]thiophenes and Kinetic Evidence for a Heck-type Pathway.
J. Am. Chem. Soc. 2016, 138, 1677−1683. (c) Colletto, C.; Panigrahi,
́
A.; Fernandez-Casado, J.; Larrosa, I. Ag(I)−C−H Activation Enables
Near-Room-Temperature Direct α-Arylation of Benzo[b]thiophenes.
J. Am. Chem. Soc. 2018, 140, 9638−9643.
(13) Ravi Kumar, D.; Satyanarayana, G. Domino Oxidative [Pd]-
Catalysis: One-Pot Synthesis of Fluorenones Starting from Simple
Benzylamines and Iodo Arenes. Org. Lett. 2015, 17, 5894−5897.
E
DOI: 10.1021/acs.orglett.9b01679
Org. Lett. XXXX, XXX, XXX−XXX