Transition-Metal-Free Site-Selective γ-C(sp2)-H Monoiodination of Arenes Directed by an Aliphatic Keto Group

Article abstract of DOI:10.1021/acs.orglett.0c01466

A general γ-C(sp2)-H iodination method directed by an aliphatic keto group has been developed under transition-metal-free conditions for the first time, generating iodoarenes in good to excellent yields with excellent site selectivity. This protocol features a wide range of aryl-substituted ketones, short reaction times, mild reaction conditions, and scalable synthetic procedures. A possible reaction mechanism was also proposed based on several control experiments.

Full text of DOI:10.1021/acs.orglett.0c01466

pubs.acs.org/OrgLett
Letter
Transition-Metal-Free Site-Selective γ‑C(sp2)−H Monoiodination of
Arenes Directed by an Aliphatic Keto Group
Hong-Li Bian, Shi-Zhong Tang, Meng-En Chen, Xiao-Ming Zhang, Jian-Wei Lv, Xiao-Wei Chen,
Feng-Ming Qi, Shi-Wu Chen,* and Fu-Min Zhang*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01466
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A general γ-C(sp2)−H iodination method directed
by an aliphatic keto group has been developed under transition-
metal-free conditions for the first time, generating iodoarenes in
good to excellent yields with excellent site selectivity. This protocol
features a wide range of aryl-substituted ketones, short reaction
times, mild reaction conditions, and scalable synthetic procedures.
A possible reaction mechanism was also proposed based on several control experiments.
egioselective synthesis presents a considerable challenge
to modern organic chemistry. To introduce a carbon−
Scheme 1. Outline of Preparation of Aryl Iodines Using
Directing Groups
R
carbon or carbon−heteroatom bond on arene in a site-selective
manner,1 transition-metal-catalyzed, directing group (DG)
assisted transformation has become a popular synthetic
strategy, thereby attracting increasing interest from synthetic
communities in the past decades.2 However, preinstallation
and subsequent removal of the DG is one of the inherent
obstacles facing the research field on C−H activation.
Therefore, the transient DG strategy has been widely applied
to solve the above-mentioned problems.3 Alternatively, using
commonly occurring functionalities (e.g., ketone, ester, acid,
amide, and amine) in organic molecules as the DG is also an
attractive strategy. Unfortunately, most of these C−H bond
activation procedures still necessitate the use of transition
metals as catalysts. Considering the importance of transition-
metal-free reactions in organic synthesis,4 especially in
pharmaceutical industries, site-selective C−H bond trans-
formation with the assistance of commonly occurring DGs
under transition-metal-free conditions is highly warranted but
rarely undertaken.5
to date, which has been explored by only a small number of
researchers, including Yu, Sanford, Kapur, Chen, and Suther-
land (Scheme 1b).9 However, in comparison with their
developed carbonyl-relative directing groups (e.g., amide and
carbonyl acid) or other functional groups such as nitrile and
amine, carbonyl groups are more widely found in feedstock
compounds and functional organic molecules, and they can be
easily and diversely transformed into a series of other valuable
functionalities. Unfortunately, to the best of our knowledge,
such an aliphatic ketone has not been exploited for directed
aryl iodination under transition-metal-free conditions.10
Aryl iodine is a class of important compounds that can be
widely used as clinical drugs, agrochemicals, bioimaging
probes, imaging reagents, and highly valuable building blocks
in organic synthesis.6 Therefore, the introduction of iodine
atoms on aromatic compounds is a prolonged research topic,
and numerous synthetic methods have been explored to date.
However, site-selective installation of an iodine atom on arene
has not been perfectly addressed using classical iodination
methods. Consequently, numerous DGs have recently emerged
to assist site-selective C−H iodination of aryl compounds via
transition-metal-catalyzed transformations.7 In this context, the
involvement of a thermodynamically favored five-membered
cyclometalated complex has been well-established (Scheme
1a),7,8 while the formation of a less favorable six- or larger-
membered cyclometalated analogue has rarely been reported
Received: April 28, 2020
https://dx.doi.org/10.1021/acs.orglett.0c01466
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
Considering that the unique properties of hypervalent iodine
reagents could be used as less toxic and safer replacements of
transition metal complexes in numerous organic trans-
formations, we speculate that a suitable I+ intermediate may
be utilized as a reaction species for the site-selective iodination
of aryl compounds through a possible six-membered transition
state that is stabilized by proper solvent molecules (Scheme
1c). In this study, we report a carbonyl group-assisted γ-site
monoiodination of the C(sp2)−H bond of aryl compounds
under the transition-metal-free conditions.
To test our hypothesis, we began to screen the suitable
reaction conditions using 2-phenylcycloketone (1a) as a
substrate, I2 as a cheap iodine source, and phenyliodosodia-
cetate (PIDA) as an oxidant under an open-flask setting.11
Actually, there are some synthetic challenges in this expected
transformation. (1) The suppression of iodination at the highly
activated benzylic position, and/or the α′-position of the
carbonyl group needs to be solved;12−14 (2) the competition of
monoiodination at para- or ortho-positions is a well-known
phenomenon, especially for a substrate bearing a sterically
hindered cyclohexanone substituent at the aryl ring;15 (3)
suppression of undesired ortho- and para-position bisiodina-
tion;15 and (4) other competitive noniodination reactions may
also occur under the oxidative reaction conditions.15 After
numerous reaction media were tested, fortunately, the
expected monoiodination product 2a16 was isolated in 87%
yield when the reaction was performed in hexafluoroisopropa-
nol (HFIP), while 14% and 11% NMR yields were obtained in
CH3NO2 and CF3CH2OH, respectively (entries 1−3, Table
1). Subsequently, replacement of PIDA with other oxidants
was performed, and no better results were observed, although
PIFA, PhIO, and Selectfluor gave 43%, 62%, and 46% yields,
respectively (entries 4−6, Table 1). Then, various iodine
sources were investigated (entries 7−9, Table 1). The results
showed that the use of ZnI2 led to 78% yield, while other
tested iodine sources resulted in incomplete iodination
transformation, leading to the recovery of starting material
1a.17 To further improve the reaction outcome, the equivalent
of PIDA was studied in detail (entries 10−13, Table 1).
Notably, the best 91% isolated yield could be obtained when
the ratio of I2 and PIDA was adjusted to 0.5/0.8 equiv (entry
11). Moreover, other reaction conditions were also inves-
tigated, which showed a slight influence on the product yield.17
Therefore, the reaction parameters listed in entry 11 were
selected as the standard reaction conditions for the next
investigations.
With the standard conditions in hand, we investigated the
generality of this iodination reaction, and the experimental
results are shown in Scheme 2, demonstrating that the
a
Scheme 2. Scope of Cyclic Ketones
a
Table 1. Optimization of the Reaction Conditions
b
entry
I source (equiv)
oxidant (equiv)
solvent
yield
cd
,
1
2
3
4
5
6
7
8
9
I2 (0.5)
I2 (0.5)
I2 (0.5)
I2 (0.5)
I2 (0.5)
I2 (0.5)
ZnI2 (0.5)
KI (1.0)
NIS (1.0)
I2 (0.5)
I2 (0.5)
I2 (0.5)
I2 (0.5)
I2 (0.5)
-
PIDA (0.5)
PIDA (0.5)
PIDA (0.5)
PIFA (0.5)
PhIO (0.5)
Selectfluor (0.5)
PIDA (1.0)
PIDA (1.0)
-
PIDA (0.6)
PIDA (0.8)
PIDA (1.0)
PIDA (1.2)
-
CH3NO2
CF3CH2OH
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
14%
11%
87%
43%
62%
46%
78%
trace
43%
89%
91%
88%
85%
-
d
e
f
a
Otherwise noted, reactions were performed using ketones (0.2
mmol) in 1.0 mL of HFIP at room temperature under an air
b
c
atmosphere. The reaction was performed on a gram scale. The
d
reaction was performed at 0 °C. 1.0 equiv of I2 and 1.6 equiv of
PIDA were used.
gh
,
10
11
12
13
14
15
substituents on arene and cyclic ketone moieties slightly
affected the reaction outcomes. p- or m-Me substituents on aryl
substrates provided the desired monoiodination products 2b
and 2c in 73% and 84% yields with excellent chemo- and
regioselectivities, respectively. Other substrates bearing either
electron-donating groups (EDGs) or weak electron-with-
drawing groups (EWGs) also afforded the corresponding
products 2d−2j in good to excellent yields.17 The multi-
substituted aryl compounds were proven to be suitable
substrates, providing the expected monoiodination products
2k−2n in excellent yields. For a symmetric substrate (1p)
bearing two phenyl groups, the monoiodination on each arene
was observed, giving the product 2p in 61% yield. Notably, 2-
PIDA (0.8)
-
a
Reactions were performed using 2-phenylcyclohexanone (0.2 mmol)
in 1.0 mL solvent at room temperature under an air atmosphere.
b
c
d
e
Isolated yield. PIDA = phenyliodosodiacetate. NMR yield. PIFA
f
= phenyliodine bis(trifluoroacetate). Selectfluor = 1-chloromethyl-4-
fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate). NIS
= N-iodosuccinimide. 1.0 equiv of HOAc was added without an extra
oxidant.
g
h
B
https://dx.doi.org/10.1021/acs.orglett.0c01466
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(1-iodonaphthalen-2-yl)cyclohexan-1-one (2o) was obtained
in 87% yield under the standard conditions, without isolation
of its 3-iodinated regioisomer. This experimental result is in
accordance with the rule of the electrophilic substitution
reaction of substituted naphthyl compounds. Then, substrates
with various ring systems were subjected to the standard
reaction conditions, and cyclopentanone, cycloheptanone, oxa-
cyclohexanone, and benzocyclic ketone derivatives were all
proven to be amenable substrates, affording the corresponding
products 2q−2t in 56−86% yields. In all cases, despite
substrates bearing two sp3 C−H bonds at the α- and α′-
positions of the carbonyl group, no iodinating products on the
α- and/or α′-C sites were isolated, indicating the excellent
chemo- and regioselectivities of this iodination reaction.
Unfortunately, the substrate bearing a strong OMe at the
para-position yielded product 2u′, whose structure was further
confirmed by X-ray analysis, without the isolation of any
expected γ-C(sp2)−H iodination product 2u, presumably
because the strong orientation effect of the OMe group
surpassed that of the weak direction of the carbonyl group
during the iodination event. Additionally, substrates bearing a
NO2 group at the para-position (1v) or a CF3 group at the
meta-position (1w) of the aryl ring did not yield the desired
products 2v and 2w, respectively, and the strong EWG group
at the aryl ring may significantly affect the activity of the
electrophilic substitution reaction.
substrates as well, providing the expected monoiodinated
products 4b−4d. Notably, symmetrically di-iodinated product
4e could be obtained in 82% yield when 1.0 equiv of I2 and 1.6
equiv of PIDA were used. Subsequently, a variety of
deoxybenzoins were tested. Either EDGs or EWGs on the
benzyl moiety or benzoyl moiety in deoxybenzoins were well
tolerated, affording the desired products 4f−4o in good to
excellent yields. Notably, 1,2-diphenylethanone (3f) produced
the expected monoiodinated product (4f) in 89% isolated
yield, distinct from the reaction results of Kurosawa’s
procedure,13b which generated two oxidative products at the
benzyl position. Remarkably, when 1,2-diphenylbutan-1-one
(3p) was subjected to the standard reaction conditions,
monoiodinated product 4p could be isolated in a slightly lower
yield. Similar to cyclic ketones, acyclic ketones also generated
the monoiodinating products in a highly chemo- and
regioselective manner. In all, these results from Schemes 2
and 3 demonstrated that the current transformation is a
general monoiodination methodology in terms of both cyclic
and linear aryl-substituted ketones, in which the para-position
at the aryl ring is free of a substituent in most cases.
Further synthetic application of this γ-site iodination was
then carried out. First, two gram-scale reactions were
performed, providing the desired products 2a and 4e in
similar high yields (88% and 81% yields, respectively; Schemes
2 and 3). Moreover, considering the value of HFIP, the solvent
could be recovered with approximately 89% yield by simple
distillation at 80 °C. These results indicated that the current
iodination procedure could be utilized on a large scale using a
recoverable reaction media without decreasing the yields.
Then, in order to increase product complexity, the coupling
reactions were investigated, and the Pd-catalyzed intermolec-
ular Suzuki reaction and Sonagashira reaction of compound 2a
provided the coupling products 2aa and 2ab in 83% and 85%
yields, respectively (Scheme 4).
After investigation of cyclic substrates, we examined the
scope of acyclic aryl substrates. Notably, we found that the
iodination reaction was also compatible with acyclic ketone
substrates, and the expected monoiodinated products 4a−4o
were isolated in good to excellent yields with excellent γ-
position selectivity (Scheme 3). Phenylacetone was subjected
to the standard reaction conditions, producing the desired
product 4a in 85% yield, and its analogues proved ideal
a
Scheme 3. Scope of Acyclic Ketones
Scheme 4. Further Transformation of Product 2a
Subsequently, we focused our attention on the investigation
of the possible reaction mechanism (Scheme 5). First, in the
absence of PIDA or I2, the desired product 2a could not be
isolated, resulting in almost full recovery of the starting
material (entries 14 and 15, Table 1), which demonstrated that
the combination of I2 and PIDA is vital for this iodination.
Second, when cyclohexylbenzene 5 was subjected to the
standard reaction conditions, para-iodination product 5a was
obtained in 91% NMR yield, without the isolation of ortho-
iodination product 5b, indicating that the carbonyl group on
the cyclohexane moiety is necessary for this transformation and
that enolization may be essential for this iodination (eq 1). To
test this hypothesis, substrate 6 bearing a quaternary carbon
center was subjected to the standard reaction conditions. The
reaction could not yield the desired product 6a, and para-
iodinated product 6b was obtained in 42% NMR yield along
with the recovery of the starting material (55% yield) (eq 2).
Then, 2-phenylcyclohexan-1-ol (7) was subjected to the
standard reaction conditions, resulting in an inseparable
mixture, which was oxidized to afford product 2a (46%
a
Otherwise noted, reactions were performed using ketones (0.2
mmol) in 1.0 mL of HFIP at room temperature under an air
atmosphere. 1.0 equiv of I2 and 1.6 equiv of PIDA were used. The
reaction was performed on a gram scale. The reaction was performed
at 0 °C.
b
c
d
C
https://dx.doi.org/10.1021/acs.orglett.0c01466
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
could be stabilized by solvent molecular HFIP or higher-order
aggregates of HFIP molecules (not shown) through hydrogen
bond interactions.18 Simultaneously, PIDA, which was also
activated by HFIP,18 reacted with molecule I2 to yield a key
activated I+ species (IOAc) in situ.19 The generated IOAc was
then interacted with the resulting intermediate I-A to form the
tighter intermediate I-B due to the combined effect of
intermolecular hydrogen and halogen bonds. As a conse-
quence, this highly electrophilic iodium (I) center of IOAc
could be further activated by the action of HFIP in this
transient halogen-bonded adduct I-B. Subsequently, the
excellent site-selective iodination on the aryl ring is proceeded
by the six-membered cyclic transition state to generate enone
I-C, which was rearomatized to produce the product 2a.
In conclusion, we have developed an excellent site-selective
γ-C(sp2)−H iodination methodology for aryl compounds
using an aliphatic ketone as a directing group under
transition-metal-free conditions. The current transformation
features broad substrate scope, mild and air- and moisture-free
reaction conditions, short reaction times, and simple
manipulation, and it is also a green and scalable approach.
The current synthetic methodology is complementary to the
transition-metal-catalyzed aryl ring iodination reaction devel-
oped by other groups. The preliminary reaction mechanism
was also investigated.
Scheme 5. Some Designed Control Experiments
yield) along with compound 2a′ (19% yield) (eq 3). These
above-mentioned results further verified that the enolization is
crucial for this iodination. Moreover, when 2-benzylcyclohex-
an-1-one (8) was used as a substrate, ortho-iodinated product
8a and para-iodinated product 8a′ were isolated in an
approximately 1:1.4 ratio (eq 4). These results indicate that
the formation of a six-membered intermediate is also necessary
in the current iodination. Subsequently, when the model
reaction was performed in O-methyl HFIP (HFIP-Me), the
ortho-iodination product 2a was isolated along with para-
iodination product 2a′, indicating that the hydrogen bond
donor capacity of HFIP is also vital for the success of the site-
selective monoiodination reaction (eq 5). Finally, a set of
parallel intermolecular kinetic isotope experiments using 1a
and deuterated 1a-D5 were performed,17 and a KH/KD ratio of
approximately 1.1 implies that the C−H bond cleavage of the
aryl ring may not be a rate-determining step in the iodination
event (eq 6).
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01466.
1
Experimental procedure, characterization data, and H
and 13C NMR spectra (PDF)
Accession Codes
CCDC 1977775 and 1977777−1977787 contain the supple-
mentary 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 Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
■
Based on these control experimental results and previous
literature,18,19 we proposed a possible reaction mechanism as
shown in Scheme 6. In the presence of the HOAc or HFIP,
substrate 1a was enolized to produce intermediate I-A, which
Corresponding Authors
Fu-Min Zhang − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China; orcid.org/
0000-0001-5578-1148; Email: zhangfm@lzu.edu.cn
Shi-Wu Chen − School of Pharmacy, Lanzhou University,
Lanzhou 730000, China; Email: chenshw@lzu.edu.cn
Scheme 6. Proposed Reaction Mechanism
Authors
Hong-Li Bian − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering
and School of Pharmacy, Lanzhou University, Lanzhou
730000, China
Shi-Zhong Tang − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
Meng-En Chen − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
D
https://dx.doi.org/10.1021/acs.orglett.0c01466
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
2526. (d) Li, J.-J.; Giri, R.; Yu, J.-Q. Tetrahedron 2008, 64, 6979−
6987. (e) Li, J.-J.; Mei, T.-S.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008,
47, 6452−6455. (f) Mei, T.-S.; Wang, D.-H.; Yu, J.-Q. Org. Lett. 2010,
12, 3140−3143. (g) Wang, X.-C.; Hu, Y.; Bonacorsi, S.; Hong, Y.;
Burrell, R.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, 10326−10329.
(h) Lu, C.; Zhang, S.-Y.; He, G.; Nack, W. A.; Chen, G. Tetrahedron
2014, 70, 4197−4203. (i) Li, G.; Wan, L.; Zhang, G.; Leow, D.;
Spangler, J.; Yu, J.-Q. J. Am. Chem. Soc. 2015, 137, 4391−4397.
(j) Haines, B. E.; Xu, H.; Verma, P.; Wang, X.-C.; Yu, J.-Q.; Musaev,
D. G. J. Am. Chem. Soc. 2015, 137, 9022−9031. (k) Zhou, M.-J.; Yang,
T.-L.; Dang, L. J. Org. Chem. 2016, 81, 1006−1020. (l) Das, R.;
Kapur, M. J. Org. Chem. 2017, 82, 1114−1126. (m) Dubost, E.; Babin,
Xiao-Ming Zhang − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China; orcid.org/
0000-0002-9294-9672
Jian-Wei Lv − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
Xiao-Wei Chen − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
Feng-Ming Qi − State Key Laboratory of Applied Organic
Chemistry & College of Chemistry and Chemical Engineering,
Lanzhou University, Lanzhou 730000, China
́
V.; Benoist, F.; Hebert, A.; Barbey, P.; Chollet, C.; Bouillon, J.-P.;
Manrique, A.; Pieters, G.; Fabis, F.; Cailly, T. Org. Lett. 2018, 20,
6302−6305. (n) Kommagalla, Y.; Yamazaki, K.; Yamaguchi, T.;
Chatani, N. Chem. Commun. 2018, 54, 1359−1362. (o) Henry, M. C.;
Sutherland, A. Org. Lett. 2020, 22, 2766−2770.
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01466
(10) (a) Motati, D. R.; Uredi, D.; Watkins, E. B. Chem. Sci. 2018, 9,
1782−1788. (b) Jiao, J.-Y.; Mao, Y.-J.; Feng, A.-W.; Li, X.-F.; Li, M.-
T.; Zhang, X.-H. Tetrahedron 2017, 73, 1482−1488. (c) Nack, W. A.;
He, G.; Zhang, S.-Y.; Lu, C.; Chen, G. Org. Lett. 2013, 15, 3440−
Notes
The authors declare no competing financial interest.
́
́
3443. (d) Barluenga, J.; Alvarez-Gutierrez, J. M.; Ballesteros, A.;
ACKNOWLEDGMENTS
́
Gonzalez, J. M. Angew. Chem., Int. Ed. 2007, 46, 1281−1283.
■
(e) Espuna, G.; Arsequell, G.; Valencia, G.; Barluenga, J.; Alvarez-
̃
We are grateful to the NSFC (Nos. 21772076, 21971095, and
91956203) for financial support of this work. We also thank
Professors Ming Yang, Wei Yu, and Chun-An Fan (Lanzhou
University) for their valuable discussions. This paper is in
memory of Prof. Xuan Tian (Lanzhou University).
́
́
Gutierrez, J. M.; Ballesteros, A.; Gonzalez, J. M. Angew. Chem., Int. Ed.
2004, 43, 325−329. (f) Espuna, G.; Arsequell, G.; Valencia, G.;
̃
́
́
Barluenga, J.; Perez, M.; Gonzalez, J. M. Chem. Commun. 2000, 31,
1307−1308. (g) Yang, S. G.; Kim, Y. H. Tetrahedron Lett. 1999, 40,
6051−6054. (h) Aiso, H.; Kochi, T.; Mutsutani, H.; Tanabe, T.;
Nishiyama, S.; Kakiuchi, F. J. Org. Chem. 2012, 77, 7718−7724.
(i) Pal, P.; Singh, H.; Panda, A. B.; Ghosh, S. C. Asian J. Org. Chem.
2015, 4, 879−883.
REFERENCES
■
(1) For selectively recent reviews, see: (a) Jiao, K.-J.; Xing, Y.-K.;
Yang, Q.-L.; Qiu, H.; Mei, T.-S. Acc. Chem. Res. 2020, 53, 300−310.
(b) Dimakos, V.; Taylor, M. S. Chem. Rev. 2018, 118, 11457−11517.
(c) Hartwig, J. F. Acc. Chem. Res. 2017, 50, 549−555.
(11) (a) Tang, S.-Z.; Bian, H.-L.; Zhan, Z.-S.; Chen, M.-E.; Lv, J.-W.;
Xie, S.; Zhang, F.-M. Chem. Commun. 2018, 54, 12377−12380.
(b) Zhang, Z.-Q.; Chen, T.; Zhang, F.-M. Org. Lett. 2017, 19, 1124−
1127. (c) Tang, S.-Z.; Zhao, W.; Chen, T.; Liu, Y.; Zhang, X.-M.;
Zhang, F.-M. Adv. Synth. Catal. 2017, 359, 4177−4183. (d) Chen, T.;
Peng, R.; Hu, W.; Zhang, F.-M. Org. Biomol. Chem. 2016, 14, 9859−
9867.
(2) For selectively recent reviews, see: (a) Wu, M.-J.; Chu, J.-H. J.
Chin. Chem. Soc. 2020, 67, 399−421. (b) Rej, S.; Ano, Y.; Chatani, N.
Chem. Rev. 2020, 120, 1788−1887. (c) Dey, A.; Sinha, S. K.; Achar, T.
K.; Maiti, D. Angew. Chem., Int. Ed. 2019, 58, 10820−10843.
(3) For selectively recent review, see: (a) Sambiagio, C.;
́
́
(12) (a) Barluenga, J.; Campos-Gomez, E.; Rodríguez, D.; Gonzalez-
́
Bobes, F.; Gonzalez, J. M. Angew. Chem., Int. Ed. 2005, 44, 5851−
̈
Schonbauer, D.; Blieck, R.; Dao-Huy, T.; Pototschnig, G.; Schaaf,
5854. (b) Mo, F.; Yan, J. M.; Qiu, D.; Li, F.; Zhang, Y.; Wang, J.
Angew. Chem., Int. Ed. 2010, 49, 2028−2032.
P.; Wiesinger, T.; Zia, M. F.; Wencel-Delord, J.; Besset, T.; Maes, B.
U. W.; Schnurch, M. Chem. Soc. Rev. 2018, 47, 6603−6743. For a
̈
selectively recent reference, see: (b) Zhang, F.-L.; Hong, K.; Li, T.-J.;
Park, H.; Yu, J.-Q. Science 2016, 351, 252−256.
(13) (a) Jereb, M.; Iskra, J.; Zupan, M.; Stavber, S. Lett. Org. Chem.
2005, 2, 465−468. (b) Fukuyama, N.; Nishino, H.; Kurosawa, K. Bull.
Chem. Soc. Jpn. 1987, 60, 4363−4368. (c) Liao, X.; Stanley, L. M.;
Hartwig, J. F. J. Am. Chem. Soc. 2011, 133, 2088−2091. (d) Liao, X.;
Weng, Z.; Hartwig, J. F. J. Am. Chem. Soc. 2008, 130, 195−200.
(e) Wang, Z.; Yin, G.; Qin, J.; Gao, M.; Cao, L.; Wu, A. Synthesis
2008, 2008, 3675−3681.
(14) (a) Cano, R.; Zakarian, A.; McGlacken, G. P. Angew. Chem., Int.
Ed. 2017, 56, 9278−9290. (b) Levitre, G.; Dumoulin, A.; Retailleau,
P.; Panossian, A.; Leroux, F. R.; Masson, G. J. Org. Chem. 2017, 82,
11877−11883. (c) Yu, J.; Cui, J.; Hou, X.-S.; Liu, S.-S.; Gao, W.-C.;
Jiang, S.; Tian, J.; Zhang, C. Tetrahedron: Asymmetry 2011, 22, 2039−
2055.
(4) For selectively recent reviews, see: (a) Qin, Y.; Zhu, L.; Luo, S.
Chem. Rev. 2017, 117, 9433−9520. (b) Sun, C.-L.; Shi, Z.-J. Chem.
Rev. 2014, 114, 9219−9280. (c) Thomson, J. W.; Hatnean, J. A.;
Hastie, J. J.; Pasternak, A.; Stephan, D. W.; Chase, P. A. Org. Process
Res. Dev. 2013, 17, 1287−1292.
(5) Lv, J.; Chen, X.; Xue, X.-S.; Zhao, B.; Liang, Y.; Wang, M.; Jin,
L.; Yuan, Y.; Han, Y.; Zhao, Y.; Lu, Y.; Zhao, J.; Sun, W.-Y.; Houk, K.
N.; Shi, Z. Nature 2019, 575, 336−340.
(6) For selectively recent references, see: (a) Liu, W.; Li, J.; Huang,
C.-Y.; Li, C.-J. Angew. Chem., Int. Ed. 2020, 59, 1786−1796.
(b) Petrone, D. A.; Ye, J.; Lautens, M. Chem. Rev. 2016, 116,
8003−8104. (c) Bertrand, R.; Wagner, M.; Derdau, V.; Plettenburg,
O. Bioconjugate Chem. 2016, 27, 2281−2286.
(15) (a) Stavber, S.; Jereb, M.; Zupan, M. Synthesis 2008, 2008,
1487−1513. (b) Larock, R.; Zhang, C.-L. Aromatic Halogenation.
Comprehensive Organic Transformations: A Guide to Functional Group
Preparations; Larock, R. C., Ed.; John Wiley & Sons, Inc., 2018.
(7) For selectively recent reviews, see: (a) Das, R.; Kapur, M. Asian
J. Org. Chem. 2018, 7, 1524−1541. (b) Lied, F.; Patra, T.; Glorius, F.
Isr. J. Chem. 2017, 57, 945−952.
́
́
́
(16) Jia, Z.; Galvez, E.; Sebastian, R. M.; Pleixats, R.; Alvarez-Larena,
́
A.; Martin, E.; Vallribera, A.; Shafir, A. Angew. Chem., Int. Ed. 2014,
(8) (a) Kommagalla, Y.; Chatani, N. Org. Lett. 2019, 21, 5971−
́
53, 11298−11301.
5976. (b) Erbing, E.; Sanz-Marco, A.; Vazquez-Romero, A.;
́
(17) For the details, please see the Supporting Information.
(18) For selected reviews, see: (a) Wencel-Delord, J.; Colobert, F.
Org. Chem. Front. 2016, 3, 394−400. (b) Colomer, I.; Chamberlain,
A. E. R.; Haughey, M. B.; Donohoe, T. J. Nat. Rev. Chem. 2017, 1,
0088. (c) Sinha, S. K.; Bhattacharya, T.; Maiti, D. React. Chem. Eng.
2019, 4, 244−253. For recent references, see: (d) Zhou, Z.; Cheng,
Malmberg, J.; Johansson, M. J.; Gomez-Bengoa, E.; Martín-Matute,
B. ACS Catal. 2018, 8, 920−925.
(9) For selective references: (a) Muraki, T.; Togo, H.; Yokoyama,
M. Tetrahedron Lett. 1996, 37, 2441−2444. (b) Giri, R.; Chen, X.; Yu,
J.-Q. Angew. Chem., Int. Ed. 2005, 44, 2112−2115. (c) Kalyani, D.;
Dick, A. R.; Anani, W. Q.; Sanford, M. S. Org. Lett. 2006, 8, 2523−
E
https://dx.doi.org/10.1021/acs.orglett.0c01466
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Q.-Q.; Kurti, L. J. Am. Chem. Soc. 2019, 141, 2242−2246. (e) Arnold,
̈
̈
A. M.; Pothig, A.; Drees, M.; Gulder, T. J. Am. Chem. Soc. 2018, 140,
4344−4353. (f) Colomer, I.; Batchelor-McAuley, C.; Odell, B.;
Donohoe, T. J.; Compton, R. G. J. Am. Chem. Soc. 2016, 138, 8855−
8861.
(19) For a selective review, please see: (a) Guha, S.; Kazi, I.; Nandy,
A.; Sekar, G. Eur. J. Org. Chem. 2017, 2017, 5497−5518. For selective
references, see: (b) Achar, T. K.; Maiti, S.; Mal, P. Org. Biomol. Chem.
2016, 14, 4654−4663. (c) Gottam, H.; Vinod, T. K. J. Org. Chem.
2011, 76, 974−977.
F
https://dx.doi.org/10.1021/acs.orglett.0c01466
Org. Lett. XXXX, XXX, XXX−XXX