A Fast Track to Indoles and Annulated Indoles through ortho- vs ipso-Amination of Aryl Halides

Article abstract of DOI:10.1021/acs.orglett.9b04202

A complementary site selective ortho- vs ipso-amination of aryl halides using non-electrophilic amine sources for construction of indole scaffolds is reported. A palladium-catalyzed alkyne insertion/C-H activation/palladacycle amination via merger of three easily diversified components including iodoarenes, alkynes, and amines delivers indoles with different substitution patterns even in gram scales. By employing ortho-bromoanilines, a consecutive annulative π-extension of indoles proceeds to construct indolo[1,2-f]phenanthridine scaffolds via four C-C and C-N bond formations in one pot.

Full text of DOI:10.1021/acs.orglett.9b04202

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
A Fast Track to Indoles and Annulated Indoles through ortho- vs
ipso-Amination of Aryl Halides
Farnaz Jafarpour,*,† Mehran Ghasemi,‡ Farid Mohaghegh,† Sara Asgari,† and Azizollah Habibi*,‡
†School of Chemistry, College of Science, University of Tehran, 14155-6455 Tehran, Iran
‡Faculty of Chemistry, Kharazmi University, No. 43. Mofateh Street, Enghelab Ave., 15719-14911 Tehran, Iran
S
* Supporting Information
ABSTRACT: A complementary site selective ortho- vs ipso-
amination of aryl halides using non-electrophilic amine
sources for construction of indole scaffolds is reported. A
palladium-catalyzed alkyne insertion/C−H activation/pallada-
cycle amination via merger of three easily diversified
components including iodoarenes, alkynes, and amines
delivers indoles with different substitution patterns even in
gram scales. By employing ortho-bromoanilines, a consecutive
annulative π-extension of indoles proceeds to construct
indolo[1,2-f]phenanthridine scaffolds via four C−C and C−
N bond formations in one pot.
of anilines with alkynes via an ortho C−H functionalization
he indole scaffold, one of the most important class of
Theterocycles, is ubiquitous in a wide variety of organisms received substantial attention (Scheme 1a, X = H).7 However,
and biologically active structures.1 Many drugs currently on the
market contain an indole core nucleus.2 Some indole ring-
containing drug molecules include Vincristine, Reserpine,
Indomethacine, Amedaline, Delavirdine, etc.3 Despite more
than 10 decades of numerous efforts and various strategies
developed, organic chemists continue to search for more
straightforward and economical ways to construct the pyrrole
side of these privillaged structural motifs.4
the direct approach from readily available anilines by C−H
activation remained a challenging task. Afterward, the directed
transition-metal-catalyzed C−H bond functionalization strat-
egy pioneered by Fagnou appeared as an attractive strategy in
cyclization reactions for broader substrate scope and higher
atom economy (Scheme 1b).8 These processes are associated
with some limitations including the requisite for preinstallment
of directing groups (DG) and their removal after construction
of indole. Some complementary reports also included
preinstallment of olefinic parts on the nitrogen9 or arene
sides10 of the anilines (Scheme 1c and 1d, respectively).
Despite significant achievements, in all the preparative
methods offered, the benzoic ring of indoles is built up of the
aryl section of anilines thus comprising limited scope and
applications. Building on these pioneering works, new
synthetic approaches based on the assembly of indole nucleus
directly from more easily diversified building blocks may find
great interest and applications and open a new avenue for
designing more efficient processes through indole ring
constructions.11
In situ generated C,C-palladacycles generally prepared from
aryl halides are relevant intermediates in Pd-catalyzed reactions
utilized to develop ortho-functionalizations and new trans-
formations.12,13 In this regard several alkylations and arylations
of palladacycles have been fulfilled. However, amination of
C,C-palladacycles is rarely considered and mainly limited to
electrophilic nitrogen sources.14 Recently, Zhang et al.
developed an amination reaction of C,C-palladacycles derived
Since Larock’s first report on indole synthesis in 1991,5
transition-metal-catalyzed cyclization of o-haloanilines and
alkynes has emerged as the most widely adopted protocols
toward 2,3-disubstituted indoles and is widely used (Scheme
1a, X = I, Cl, Br, N2).6 However, the requisite for untrival
prehalogention or alkynylation of aniline coupling partners and
the use of strong bases restricted the practicality of these
reactions. To fulfill the prerequisite in terms of a more
sustainable and economical strategy, the oxidative annulation
Scheme 1. Transition-Metal-Catalyzed Annulation of
Anilines
Received: November 23, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b04202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
from iodoarenes and alkynes employing di-tert-butyldiaziridi-
%) and NaHCO3 (2 equiv) in DMF at 110 °C, the desired
indole 4a was obtained in a promising 90% yield (Table 1,
none to construct indoles (Scheme 2a).15 Despite the
a
Scheme 2. Amine Sources for Amination of C,C-
Palladacycles in Construction of 2,3-Difunctionalized
Indoles
Table 1. Optimization of Reaction Conditions
b
entry
change from standard conditions
yield
1
2
standard conditions
no Pd catalayst
90
0
3
4
5
6
7
8
9
10
11
12
13
PdCl2 instead of Pd(OAc)2
Pd(dba)2 instead of Pd(OAc)2
no NaHCO3
K2CO3 instead of NaHCO3
Cs2CO3 instead of NaHCO3
KOAc instead of NaHCO3
K3PO4 instead of NaHCO3
DMSO instead of DMF
chlorobenzene instead of DMF
ACN instead of DMF
44
48
25
78
71
66
69
76
21
29
trace
THF instead of DMF
a
Reaction conditions: Aryl halide (0.1 mmol), acetylene (1 equiv),
amine (2 equiv), Pd catalyst (10 mol %), base (2 equiv), solvent (1
mL), 110 °C, 18 h. Isolated yields.
b
significance of this contribution the scope of indoles obtained
by this course was limited to N-tert-butylindoles. Lautens
group also have described an intermolecular amination of
arene norbornene palladacycles with highly strained 2H-
azirines to build the pyrrole side of indoles (Scheme 2b).16
Inspired by these pioneering works and following our
interest in palladacycles,17 we envisioned that synthesis of 2,3-
disubstituted N-aryl(alkyl)indoles might be accessed through a
cascade three-component cycloaddition of haloarenes, alkynes,
and more simple and accessible nitrogen sources such as
anilines and amines. However, realizing such a cascade owing
to various competing reactions may be highly challenging.
First, a highly reactive alkyne is supposed to directly react with
iodoarene to construct various carbocycles such as fluorenes,18
phenanthrenes,19 and naphthalenes.20 Second, anilines and
alkynes are supposed to provide free NH-indoles via classical
Larock reaction.5 Last, an ipso-amination of iodoarene via
Buchwald−Hartwig reaction may be an important competing
reaction.21
Herein, we describe the realization of a palladium-catalyzed
annulation cascade that allows the facile synthesis of a variety
of valuable 1,2,3-highly functionalized indoles, incorporating
three easily diversified building blocks: haloarenes, alkynes, and
anilines. Setting the potentially competitive ipso-amination as
well as benzannulation of iodoarene with an alkyne is key to
the success of this domino reaction. Furthermore, by
employing ortho-bromo anilines as the amine coupling partner,
an extra intramolecular arylation leads to two new rings and
four C−C and C−N bond formations for construction of
indolo[1,2-f ]phenanthridine scaffolds in one pot.
entry 1). The reaction was totally suppressed when the
palladium catalyst was removed (entry 2). Screening reaction
conditions with respect to palladium salts revealed Pd(OAc)2
to be the most optimal (entries 3−4). While NaHCO3
provided higher yields than other bases such as K2CO3,
Cs2CO3, KOAc, and K3PO4, its removal significantly decreased
the cyclization yield (entries 5−9, for more details see
Supporting Information). Compared to DMF, although
DMSO gave a comparable result, other solvents including
chlorobenzene, ACN, THF, etc. were undesirable (entries 10−
13).
With optimized conditions in hand, we examined the
generality and substrate scope of the palladium-catalyzed three-
component coupling cascade for synthesis of multifunctional-
ized indoles. Ortho-substituted anilines containing alkyl and
alkoxy groups exhibited high to excellent reactivity to produce
indoles 4a−c in 75−90% yields (Scheme 3, entries 1−3).
Likewise, para-substituted anilines containing alkoxy and
susceptible bromo and chloro groups provided the desired
products 4d−f and 4i in 76−89% yields where the halo groups
were preserved in the course of the reaction providing a
synthetically useful handle for further functionalizations
(entries 4−6 and 9). The method worked well for anilines
bearing electron-withdrawing groups as well, and the desired
products were obtained albeit in lower yields (entries 7 and
11). Electron-neutral aniline also participated well in this
reaction to afford 1,2,3-triphenyl indole 4h in 83% yield (entry
8). Turning our attention to the scope of iodoarene coupling
partner, we realized that the procedure tolerates a range of
substitution patterns and functional groups on this substrate.
Various electron-rich and deficient iodoarenes exhibited good
reactivity under the optimized reaction conditions to afford the
desired products in good to high yields (entries 12−18). The
reaction was also amenable to naphthalene amines resulting in
To realize the palladium-catalyzed arene/alkyne/amine
cyclization cascade, iodobenzene 1a, 2-methoxy aniline 2a,
and diphenyl acetylene 3a were initially combined under
various reaction conditions. After vigorous optimization, we
were grateful to find that the cascade indeed did proceed in the
presence of a palladium catalyst to afford 1,2,3-triarylindole 4a.
Under the standard conditions employing Pd(OAc)2 (10 mol
B
DOI: 10.1021/acs.orglett.9b04202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 3. Reaction Scope for Construction of N-Aryl and N-Alkylindoles
a
Reactions performed on a 0.1 mmol scale with iodoarene (1 equiv), alkyne (1 equiv), amine (2 equiv), Pd(OAc)2 (10 mol %), DMF (1 mL), 110
b
°C, 18 h. 3.0 mmol of 1 were used.
sterically crowded indoles 4s−u in moderate to good yields,
which had not been previously possible in any other way
(entries 19−21).
Intriguingly, when we tried to expand the alkyne scope to
aryl alkyl-disubstituted alkynes, assembly of unsymmetrically
2,3-disubstituted indoles with an absolute regioselectivity was
realized under standard reaction conditions (entries 35−37,
yields 50−73%). The observed high regioselectivity is
attributed to a carbopalladation sequence of the internal
alkyne in which the relatively large phenyl group of the
arylpalladium species approach the internal alkyne from the
less hindered end of the internal alkyne due to steric hindrance
and replaces the more bulkier group at the 2-position.22
To our satisfaction, when 2-bromoaniline as the aminating
agent was employed in this multicomponent cyclization
process, a fascinating successive cyclization via an intra-
molecular palladium-catalyzed direct arylation tracked carbo-
By employing benzylamines instead of anilines, even
superior results were obtained so that the desired targets
were provided in up to 95% yield (entries 22−24). Motivated
by these results, we sought to apply this strategy to the simple
production of N-alkyl 2,3-diarylindoles. The results showed
that three-component cyclization reaction of iodoarenes,
diphenylacetylene, and aliphatic amines proceeded smoothly
in the same manner to furnish the anticipated N-alkyl indoles
in 45−92% yields under the optimized reaction conditions
(entries 25−34). Notably, a yield of 85% was still obtained
when the reaction was scaled up to 3.0 mmol (entry 24).
C
DOI: 10.1021/acs.orglett.9b04202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
palladation/amination cascade to afford the promising
indolophenanthridine scaffold 6a practically in a single
synthetic sequence in 87% isolated yield (Scheme 4, entry
Scheme 5. Control Experiments Used to Elucidate the
Reaction Mechanism
Scheme 4. Scope of Cascade Construction of
a
Indolophenanthridines
a
Reactions performed on a 0.1 mmol scale with iodoarene (1 equiv),
On the basis of the above mechanistic study and literature
precedents, a plausible mechanism for the first annulation
reaction via amination of the palladacycle C is proposed in
Scheme 6. The oxidative addition of iodoarene to palladium(0)
results in the aryl palladium species A which, on
carbopalladation reaction with alkyne,23 forms styryl palladium
species B. Subsequent intramolecular C−H activation via a
five-membered palladacycle19e gives palladacycle C. Next, an
uncommon trapping of the palladacycle with aryl(alkyl)amines
occurs to develop ortho-amination of iodoarene. Formation of
palladium-amine complex E and subsequent reductive
elimination finish the intriguing dual amination of an arene
and alkyne to construct the pyrrole side of the indole.
Furthermore, by employing an ortho-bromoaniline coupling
partner, the annulation reaction proceeds even in a more
unusual manner. Although all previous reports have evidenced
an oxidative addition of the chelating ortho-haloanilines to
Pd(II) species for construction of a Pd(IV) complex,24
however, our observation demonstrates an unprecedented
direct amination of the palladacycle with ortho-bromoanilines
in contrast (Scheme 6b, G vs F). An ultimate reductive
elimination leads to the indolophenanthridine 6 adduct and
regeneration of palladium(0).25
In conclusion we have uncovered a palladium-catalyzed
annulation cascade for construction of highly substituted
indoles from merger of three easily diversified components.
This method represents the first example of forming C−N
bonds at the ortho-carbon via amination of C,C-palladacycles
with nonelectrophilic nitrogen sources. Accordingly, this
controllable domino reaction enables a rapid access to a
diverse range of indoles including several previously unsynthe-
sized scaffolds mostly in high to excellent yields. In addition,
the cascade cyclization of the same substrates employing o-
alkyne (1 equiv), 2-bromoaniline (2 equiv), Pd(OAc)2 (10 mol %),
DMF (1 mL), 110 °C, 18 h.
1). This process involves four Csp2−Csp2 and Csp2−N bond
formations in one process and involves an unprecedented
feasible construction of the polycyclic fused indoles directly
from readily accessible starting materials. To test the feasibility
and scope of the domino cyclization, some o-, m-, and p-
substituted iodoarenes were coupled with diphenylacetylene
and bromoanilines, where the desired products were obtained
in moderate to high yields (entries 2−6, yields 50−84%). The
structure of 6f was unambiguously confirmed by single-crystal
X-ray diffraction (CCDC 1946006).
To gain insight into the reaction mechanism and differ-
entiate between three parallel plausible paths, some control
experiments using 4-chloroiodobenzene, diphenyl acetylene,
and 2-methoxy aniline were carried out (Scheme 5). A
plausible early ipso-amination via Buchwald−Hartwig reaction
trailed with the annulation reaction would result in two
possible isomers (Scheme 5a, I and II), which none were
detected in the reaction course. Furthermore, when a
diphenylamine was subjected to the standard conditions,
only traces of the desired indole 4h was collected (Scheme
5b). Furthermore, a domino Larock indole synthesis/
Buchwald N-arylation of the in situ generated indole may
not be the choice, as the substitution pattern of the indole
achieved would be quite different (Scheme 5c). These results
suggest that a palladacycle is a more likely intermediate in the
course of indole construction. A proposed primary palladacycle
development followed by amination would render 6-chloro
substituted indole 4n as obtained in this process in 95%
isolated yield (Scheme 5d).
D
DOI: 10.1021/acs.orglett.9b04202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
ORCID
Scheme 6. Plausible Mechanism Accounting for Domino
Annulation Reactions
Farnaz Jafarpour: 0000-0001-5242-2748
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge the financial support of University
of Tehran and Kharazmi University.
■
REFERENCES
■
(1) For reviews, see: (a) Zou, Y.; Smith, A. B., 3rd J. Antibiot. 2018,
71, 185. (b) Zhang, M.-Z.; Chen, Q.; Yang, G.-F. Eur. J. Med. Chem.
2015, 89, 421. (c) Sharma, V.; Kumar, P.; Pathak, D. J. Heterocycl.
Chem. 2010, 47, 491. (d) Kochanowska-Karamyan, A. J.; Hamann, M.
T. Chem. Rev. 2010, 110, 4489. (e) Humphrey, G. R.; Kuethe, J. T.
Chem. Rev. 2006, 106, 2875. (f) Kawasaki, T.; Higuchi, K. Nat. Prod.
Rep. 2005, 22, 761.
(2) Taylor, R. D.; MacCoss, M.; Lawson, A. D. G. J. Med. Chem.
2014, 57, 5845.
(3) Kaushik, N. K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.;
Verma, A. K.; Choi, E. H. Molecules 2013, 18, 6620.
(4) For reviews, see: (a) Youn, S. W.; Ko, T. Y. Asian J. Org. Chem.
2018, 7, 1467. (b) Agasti, S.; Dey, A.; Maiti, D. Chem. Commun. 2017,
53, 6544. (c) Karchava, A. V.; Melkonyan, F. S.; Yurovskaya, M. A.
Chem. Heterocycl. Compd. 2012, 48, 391. (d) Shiri, M. Chem. Rev.
2012, 112, 3508. (e) Taber, D. F.; Tirunahari, P. K. Tetrahedron
2011, 67, 7195. (f) Cacchi, S.; Fabrizi, G. Chem. Rev. 2011, 111,
PR215. (g) Ackermann, L. Synlett 2007, 2007, 507. (h) Humphrey, G.
R.; Kuethe, J. T. Chem. Rev. 2006, 106, 2875. (i) Cacchi, S.; Fabrizi,
G. Chem. Rev. 2005, 105, 2873.
(5) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689.
(6) For selected examples, see: (a) Onishi, K.; Oikawa, K.; Yano, H.;
Suzuki, T.; Obora, Y. RSC Adv. 2018, 8, 11324. (b) Weng, W.-Z.; Xie,
J.; Zhang, B. Org. Biomol. Chem. 2018, 16, 3983. (c) Srinivas, K.;
Saiprathima, P.; Balaswamy, K.; Rao, M. M. J. Organomet. Chem.
2013, 741−742, 162. (d) Batail, N.; Dufaud, V.; Djakovitch, L.
Tetrahedron Lett. 2011, 52, 1916. (e) Monguchi, Y.; Mori, S.; Aoyagi,
S.; Tsutsui, A.; Maegawa, T.; Sajiki, H. Org. Biomol. Chem. 2010, 8,
3338. (f) Batail, N.; Bendjeriou, A.; Lomberget, T.; Barret, R.;
Dufaud, V.; Djakovitch, L. Adv. Synth. Catal. 2009, 351, 2055.
(g) Cui, X.; Li, J.; Fu, Y.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2008,
49, 3458. (h) Shen, M.; Li, G.; Lu, B. Z.; Hossain, A.; Roschangar, F.;
Farina, V.; Senanayake, C. H. Org. Lett. 2004, 6, 4129.
(7) (a) Hermann, G. N.; Jung, C. L.; Bolm, C. Green Chem. 2017,
19, 2520. (b) Cheng, H.; Hernandez, J. G.; Bolm, C. Org. Lett. 2017,
19, 6284. (c) Shen, D.; Han, J.; Chen, J.; Deng, H.; Shao, M.; Zhang,
H.; Cao, W. Org. Lett. 2015, 17, 3283. (d) Zhang, G.; Yu, H.; Qin, G.;
Huang, H. Chem. Commun. 2014, 50, 4331. (e) Chen, X.; Li, X.;
Wang, N.; Jin, J.; Lu, P.; Wang, Y. Eur. J. Org. Chem. 2012, 2012,
4380. (f) Shi, Z.; Zhang, C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao, N.
Angew. Chem., Int. Ed. 2009, 48, 4572.
(8) For selected examples, see: (a) Shang, Y.; Jonnada, K.; Yedage, S.
L.; Tu, H.; Zhang, X.; Lou, X.; Huang, S.; Su, W. Chem. Commun.
2019, 55, 9547. (b) Xu, F.; Li, Y.-J.; Huang, C.; Xu, H.-C. ACS Catal.
2018, 8, 3820. (c) Liang, Y.; Jiao, N. Angew. Chem., Int. Ed. 2016, 55,
4035. (d) Lu, Q.; Vasquez-Cespedes, S.; Gensch, T.; Glorius, F. ACS
Catal. 2016, 6, 2352. (e) Zhang, Z.-Z.; Liu, B.; Xu, J.-W.; Yan, S.-Y.;
Shi, B.-F. Org. Lett. 2016, 18, 1776. (f) Hoshino, Y.; Shibata, Y.;
Tanaka, K. Adv. Synth. Catal. 2014, 356, 1577. (g) Zhao, D.; Shi, Z.;
Glorius, F. Angew. Chem., Int. Ed. 2013, 52, 12426. (h) Wang, C.; Sun,
H.; Fang, Y.; Huang, Y. Angew. Chem., Int. Ed. 2013, 52, 5795.
(i) Wang, C.; Huang, Y. Org. Lett. 2013, 15, 5294. (j) Song, W.;
Ackermann, L. Chem. Commun. 2013, 49, 6638. (k) Liu, B.; Song, C.;
Sun, C.; Zhou, S.; Zhu, J. J. Am. Chem. Soc. 2013, 135, 16625.
(l) Ackermann, L.; Lygin, A. V. Org. Lett. 2012, 14, 764. (m) Huestis,
M. P.; Chan, L. N.; Stuart, D. R.; Fagnou, K. Angew. Chem., Int. Ed.
2011, 50, 1338. (n) Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J.
haloanilines leads to an unusual construction of indolo[1,2-
f]phenanthridine frameworks in competitive pathways. Our
novel method for construction of indoles bearing flexible
substituents at each point of the indole ring complements the
classic routes to highly substituted indoles. The method is
scalable and mild and obviates any requisite for directing
groups or oxidants. Detailed mechanistic studies to realize the
dual C−N bond formation steps are underway.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b04202.
Experimental procedures and compound characteriza-
1
tion data, including the H/13C NMR spectra (PDF)
Accession Codes
CCDC 1946006 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: jafarpur@khayam.ut.ac.ir.
*E-mail: habibi@khu.ac.ir.
E
DOI: 10.1021/acs.orglett.9b04202
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Am. Chem. Soc. 2010, 132, 18326. (o) Chen, J.; Song, G.; Pan, C.-L.;
Li, X. Org. Lett. 2010, 12, 5426−5429. (p) Stuart, D. R.; Bertrand-
Laperle, M.; Burgess, K. M. N.; Fagnou, K. J. Am. Chem. Soc. 2008,
130, 16474.
(9) (a) Tian, X.; Song, L.; Rudolph, M.; Rominger, F.; Hashmi, A. S.
K. Org. Lett. 2019, 21, 4327. (b) Wei, Y.; Deb, I.; Yoshikai, N. J. Am.
Chem. Soc. 2012, 134, 9098. (c) Neumann, J. J.; Rakshit, S.; Droge,
T.; Wurtz, S.; Glorius, F. Chem. - Eur. J. 2011, 17, 7298. (d) Wurtz, S.;
Rakshit, S.; Neumann, J. J.; Droge, T.; Glorius, F. Angew. Chem., Int.
Ed. 2008, 47, 7230.
(10) (a) Cao, W.-B.; Xu, X.-P.; Ji, S.-J. Adv. Synth. Catal. 2019, 361,
1771. (b) Zhao, C.-Y.; Li, K.; Pang, Y.; Li, J.-Q.; Liang, C.; Su, G.-F.;
Mo, D.-L. Adv. Synth. Catal. 2018, 360, 1919. (c) Andries-Ulmer, A.;
Brunner, C.; Rehbein, J.; Gulder, T. J. Am. Chem. Soc. 2018, 140,
13034. (d) Ghorai, J.; Reddy, A. C. S.; Anbarasan, P. Chem. - Asian J.
2018, 13, 2499. (e) Yuan, K.; Liu, L.; Chen, J.; Guo, S.; Yao, H.; Lin,
A. Org. Lett. 2018, 20, 3477. (f) Maity, S.; Zheng, N. Angew. Chem.,
Int. Ed. 2012, 51, 9562.
(11) For some recent advancements, see: (a) Shan, X.-H.; Zheng,
H.-X.; Yang, B.; Tie, L.; Fu, J.-L.; Qu, J.-P.; Kang, Y.-B. Nat. Commun.
2019, 10, 908. (b) Mao, J.; Wang, Z.; Xu, X.; Liu, G.; Jiang, R.; Guan,
H.; Zheng, Z.; Walsh, P. Angew. Chem., Int. Ed. 2019, 58, 11033.
(c) Zhang, B.-S.; Li, Y.; Zhang, Z.; An, Y.; Wen, Y.-H.; Gou, X.-Y.;
Quan, S.-Q.; Wang, X.-G. J. Am. Chem. Soc. 2019, 141, 9731.
(d) Bugaenko, D. I.; Dubrovina, A. A.; Yurovskaya, M. A.; Karchava,
A. V. Org. Lett. 2018, 20, 7358.
(17) (a) Jafarpour, F.; Jalalimanesh, N.; Teimouri, M.;
Shamsianpour, M. Chem. Commun. 2015, 51, 225. (b) Jafarpour, F.;
Hazrati, H. Adv. Synth. Catal. 2010, 352, 363. (c) Jafarpour, F.;
Ashtiani, P. T. J. Org. Chem. 2009, 74, 1364. (d) Jafarpour, F.;
Lautens, M. Org. Lett. 2006, 8, 3601.
(18) (a) Zhou, B.; Wu, Z.; Qi, W.; Sun, X.; Zhang, Y. Adv. Synth.
Catal. 2018, 360, 4480. (b) Chan, K.-T.; Tsai, Y.-H.; Lin, W.-S.; Wu,
J.-R.; Chen, S.-J.; Liao, F.-X.; Hu, C.-H.; Lee, H. M. Organometallics
2010, 29, 463. (c) Larock, R. C.; Tian, Q. J. Org. Chem. 2001, 66,
7372. (d) Tian, Q.; Larock, R. C. Org. Lett. 2000, 2, 3329.
(19) (a) Zuo, Z.; Wang, H.; Fan, L.; Liu, J.; Wang, Y.; Luan, X.
Angew. Chem., Int. Ed. 2017, 56, 2767. (b) Iwasaki, M.; Araki, Y.; Iino,
S.; Nishihara, Y. J. Org. Chem. 2015, 80, 9247. (c) Catellani, M.;
Motti, E.; Baratta, S. Org. Lett. 2001, 3, 3611. (d) Dyker, G.; Kellner,
A. J. Organomet. Chem. 1998, 555, 141. (e) Dyker, G.; Kellner, A.
Tetrahedron Lett. 1994, 35, 7633.
(20) (a) Lee, C.-W.; Liu, E.-C.; Wu, Y.-T. J. Org. Chem. 2015, 80,
10446. (b) Bej, A.; Chakraborty, A.; Sarkar, A. RSC Adv. 2013, 3,
15812.
(21) For a very recent review, see: Dorel, R.; Grugel, C. P.; Haydl, A.
H. Angew. Chem., Int. Ed. 2019, 58, 17118 and references cited
therein.
(22) Zhou, C.; Larock, R. C. J. Org. Chem. 2005, 70, 3765.
(23) For carbopalladation of alkynes see: (a) Larock, R. C. Topics in
Organometallic Chemistry; Springer: Berlin, 2005; p 147. (b) Larock,
R. C. Pure Appl. Chem. 1999, 71, 1435.
(24) Della Ca, N.; Maestri, G.; Malacria, M.; Derat, E.; Catellani, M.
Angew. Chem., Int. Ed. 2011, 50, 12257.
(12) (a) Albrecht, M. Chem. Rev. 2010, 110, 576. (b) Dupont, J.;
Pfeffer, M. Palladacycles: Synthesis, Characterization and Applications;
Wiley-VCH: Weinheim, 2008. (c) Dupont, J.; Consorti, C. S.;
Spencer, J. Chem. Rev. 2005, 105, 2527. (d) Campora, J.; Palma, P.;
Carmona, E. Coord. Chem. Rev. 1999, 193−195, 207.
(25) For intramolecular arylation mechanism, see: Garcia-Cuadrado,
D.; Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc.
2006, 128, 1066 and references cited therein.
(13) For selected examples, see: (a) Guo, S.; Li, P.; Guan, Z.; Cai,
L.; Chen, S.; Lin, A.; Yao, H. Org. Lett. 2019, 21, 921. (b) Zhou, B.;
Lu, A.; Shao, C.; Liang, X.; Zhang, Y. Chem. Commun. 2018, 54,
10598. (c) Lu, A.; Ji, X.; Zhou, B.; Wu, Z.; Zhang, Y. Angew. Chem.,
Int. Ed. 2018, 57, 3233. (d) Yang, L.; Melot, R.; Neuburger, M.;
Baudoin, O. Chem. Sci. 2017, 8, 1344. (e) Yao, T.; He, D. Org. Lett.
́
́
́
2017, 19, 842. (f) Perez-Gomez, M. M.; Hernandez-Ponte, S.;
́
Bautista, D.; García-Lopez, J.-A. Chem. Commun. 2017, 53, 2842.
(g) Ye, J.; Shi, Z.; Sperger, T.; Yasukawa, Y.; Kingston, C.;
Schoenebeck, F.; Lautens, M. Nat. Chem. 2017, 9, 361. (h) Hu, T.-
J.; Zhang, G.; Chen, Y.-H.; Feng, C.-G.; Lin, G.-Q. J. Am. Chem. Soc.
́
́
́
́
2016, 138, 2897. (i) Gutierrez-Bonet, A.; Julia-Hernandez, F.; de Luis,
́
́
B.; Martin, R. J. Am. Chem. Soc. 2016, 138, 6384. (j) Perez-Gomez,
M.; García-Lopez, J.-A. Angew. Chem., Int. Ed. 2016, 55, 14389.
́
(k) Yoon, H.; Lossouarn, A.; Landau, F.; Lautens, M. Org. Lett. 2016,
18, 6324. (l) Chen, D.; Shi, G.; Jiang, H.; Zhang, Y.; Zhang, Y. Org.
Lett. 2016, 18, 2130. (m) Wang, M.; Zhang, X.; Zhuang, Y.-X.; Xu, Y.-
H.; Loh, T.-P. J. Am. Chem. Soc. 2015, 137, 1341. (n) Gao, D.-W.;
Yin, Q.; Gu, Q.; You, S.-L. J. Am. Chem. Soc. 2014, 136, 4841.
(o) Sickert, M.; Weinstabl, H.; Peters, B.; Hou, X.; Lautens, M.
Angew. Chem., Int. Ed. 2014, 53, 5147. (p) Deng, R.; Huang, Y.; Ma,
X.; Li, G.; Zhu, R.; Wang, B.; Kang, Y.-B.; Gu, Z. J. Am. Chem. Soc.
2014, 136, 4472. (q) Piou, T.; Bunescu, A.; Wang, Q.; Neuville, L.;
Zhu, J. Angew. Chem., Int. Ed. 2013, 52, 12385. (r) Liu, Z.; Larock, R.
C. Angew. Chem., Int. Ed. 2007, 46, 2535. (s) Masselot, D.; Charmant,
J. P. H.; Gallagher, T. J. Am. Chem. Soc. 2006, 128, 694. (t) Mota, A.
J.; Dedieu, A.; Bour, C.; Suffert, J. J. Am. Chem. Soc. 2005, 127, 7171.
(u) Bour, C.; Suffert, J. Org. Lett. 2005, 7, 653. (v) Zhao, J.; Larock, R.
C. Org. Lett. 2005, 7, 701. (w) Campo, M. A.; Larock, R. C. J. Am.
Chem. Soc. 2002, 124, 14326. (x) Karig, G.; Moon, M.-T.; Thasana,
N.; Gallagher, T. Org. Lett. 2002, 4, 3115. (y) Dyker, G. Angew.
Chem., Int. Ed. Engl. 1994, 33, 103. (z) Dyker, G. Angew. Chem., Int.
Ed. Engl. 1992, 31, 1023.
(14) For a recent review, see: Wang, J.; Dong, G. Chem. Rev. 2019,
119, 7478.
(15) Zhou, B.; Wu, Z.; Ma, D.; Ji, X.; Zhang, Y. Org. Lett. 2018, 20,
6440.
(16) Candito, D. A.; Lautens, M. Org. Lett. 2010, 12, 3312.
F
DOI: 10.1021/acs.orglett.9b04202
Org. Lett. XXXX, XXX, XXX−XXX