Selective C(sp2)-H Halogenation of "click" 4-Aryl-1,2,3-triazoles

Article abstract of DOI:10.1021/acs.orglett.7b00275

Selective bromination reactions of "click compounds" are described. Electron-neutral and electron-deficient arenes selectively undergo unprecedented Pd-catalyzed C-H ortho-halogenations assisted by simple triazoles as modular directing groups, whereas electron-rich arenes are regioselectively halogenated following an electrophilic aromatic substitution reaction pathway. These C-H halogenation procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools of utmost importance for the late-stage diversification of "click compounds". The characterization of a triazole-containing palladacycle and density functional theory studies supported the mechanism proposal.

Full text of DOI:10.1021/acs.orglett.7b00275

Letter
pubs.acs.org/OrgLett
Selective C(sp2)−H Halogenation of “Click” 4‑Aryl-1,2,3-triazoles
Asier Goitia, Enrique Gomez-Bengoa, and Arkaitz Correa*
́
Department of Organic Chemistry-I, University of the Basque Country (UPV-EHU), Joxe Mari Korta R&D Center, Av Tolosa 72,
20018 Donostia-San Sebastian, Spain
́
S
* Supporting Information
ABSTRACT: Selective bromination reactions of “click compounds” are
described. Electron-neutral and electron-deficient arenes selectively
undergo unprecedented Pd-catalyzed C−H ortho-halogenations assisted
by simple triazoles as modular directing groups, whereas electron-rich
arenes are regioselectively halogenated following an electrophilic
aromatic substitution reaction pathway. These C−H halogenation
procedures exhibit a wide group tolerance, complement existing bromination procedures, and represent versatile synthetic tools
of utmost importance for the late-stage diversification of “click compounds”. The characterization of a triazole-containing
palladacycle and density functional theory studies supported the mechanism proposal.
Scheme 1. Metal-Catalyzed C−H Functionalization Processes
Using “Click” 4-Aryl-1,2,3-triazoles
hecarbon−halogenbondisundoubtedlyamajorworkhorse
1
Twithin the realm of organic chemistry. In particular, aryl
halides are prevalent key motifs in a vast array of natural products
and stand out as highly versatile compounds of widespread utility
in chemical industry for the assembly of numerous relevant
medicinal products and agrochemicals.2 As a result, the
development of novel and practical halogenation procedures is
of prime synthetic value in basic and applied chemistry. Classical
approaches include electrophilic aromatic substitution (EAS),3
halogenation of aryldiazonium salts (Sandmeyer reaction),4 and
directed ortho-lithiation/halogenation sequence.5 Despite their
common use, those methods suffer from notable drawbacks such
as harsh reaction conditions often involving hazardous reagents
andmostlylackregioselectivityacrossmanysubstrateclasses. The
past decade has witnessed an increasing interest in the pursuit of
selective chelation-directed metal-catalyzed C−H halogenations
which are of paramount importance from a sustainability
standpoint.1b Although a wide variety of directing groups
(DGs) have been effectively utilized for the halogenation of
C(sp2)−H bonds,6,7 expanding the scope toother versatile motifs
remains a critical challenge of tremendous impact in the field of
C−H functionalization.8
The 1,2,3-triazole core is a prevalent heterocyclic structure in a
wide range of compounds in distinct research areas such as crop
protection, medicinal chemistry, and material sciences.9 How-
ever, itsuniquepropertieshavenotbeenfullyexploitedinthefield
of metal catalysis.10 In particular, 4-aryl-1,2,3-triazoles resulting
from the atom-economical Cu-catalyzed azide−alkyne [3 + 2]
cycloaddition (CuAAC)11 represent an ideal platform to design
novel C−H functionalization events. If successful, such methods
would constitute versatile techniques for the unexplored
chemoselective late-stage derivatization of “click compounds”.12
Most of the postfunctionalizations of 4-aryl-1,2,3-triazoles
involve C−C bond-forming processes such as Pd- or Cu-
catalyzeddirect arylationsselectively occurring attheheterocyclic
C−H bond13 (Scheme 1, route a) or triazole-assisted Ru-
catalyzed direct arylations and Pd-catalyzed acylations which
preferentially proceed at the arene while leaving the C5−H site
intact14 (Scheme 1, route b). We and others have recently
expanded the latter to Pd-catalyzed C−H oxygenation15a,b and
nitration reactions15c featuring an unconventional role of a simple
triazole scaffold as a modular DG in C−heteroatom bond-
forming processes (Scheme 1, route c). To the best of our
knowledge, the parent-challenging C−H halogenation event
directed by “click triazoles” remains unexplored (Scheme 1, route
d). If developed, this methodology would complement the
existing C−H halogenations of arenes and clearly provide
straightforward access to a variety of densely substituted
heterocyclic units in which the introduced halide motif could
behave as a temporary functional group allowing even further
structural diversification. As part of our interest in heterocyclic
chemistry,15,16 we describe herein selective C(sp2)−H halogen-
ation methods using 4-aryl-1,2,3-triazoles that feature a unique
tool to enable the buildup of molecular diversity combined with a
rapid assembly of the required heterocyclic substrates via “click
chemistry”.
Received: January 25, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00275
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Pd-Catalyzed C(sp2)−H Bromination of 1a
Scheme 2. Pd-Catalyzed C(sp2)−H Ortho-Halogenation of
a b
,
Arenes 1a−y
b
entry
change from standard conditions
none
yield (%)
1
70
0
2
without Pd(OAc)2
3
without PhI(OAc)2
27
50
4
without PivOH
c
5
without NBS
25
6
under air
55
traces
61
7
K2S2O8 instead of PhI(OAc)2
PdCl2(MeCN)2 instead of Pd(OAc)2
Pd(TFA)2 instead of Pd(OAc)2
Pd(dba)2 instead of Pd(OAc)2
CuBr2 instead of NBS
AdCO2H instead of PivOH
8
9
48
10
11
12
42
0
47
a
Reaction conditions: 1a (0.25 mmol), Pd(OAc)2 (10 mol %), NBS
(1.5 equiv), PhI(OAc)2 (1.0 equiv), PivOH (2.0 equiv), DCE (0.25
b
M) at 110 °C for 24 h under Ar. Yield of isolated product after
c
column chromatography. o-Acetoxylated triazole derivative was
obtained.
a
b
As for Table 1, entry 1. Yield of isolated product after column
c
chromatography, average of at least two independent runs. N-
Chlorosuccinimide (2.0 equiv) was used. N-Iodosuccinimide was
d
We first prepared triazole 1a upon CuAAC and study its
bromination as the model reaction.17 After careful optimization,
we found that the desired transformation was possible and o-
bromo derivative 2a was obtained in 70% yield when a
combination of Pd(OAc)2 as catalyst, N-bromosuccinimide
(NBS) as brominating agent, (diacetoxyiodo)benzene as co-
oxidant, and pivalic acid as additive was used (Table 1, entry 1).
Notably, monobromination of 1a preferentially took place in the
less hindered ortho-position, while competitive ortho-acetoxyla-
tion of the arene ring was detected in trace amounts. Control
experiments evidenced the crucial impact on reactivity of all the
variables: the reaction did not occur in the absence of palladium
catalyst (entry 2), the addition of an external oxidant was
determinant to obtain high yields (entry 3),18 the presence of a
protic acid clearly enhanced the target C−H halogenation (entry
4), and the parent ortho-acetoxylation of 1a took place in the
absence of NBS, albeit in low yields (entry 5). The use of other Pd
sources (entries 8−10), oxidants (entry 7), brominating agents
(entry 11), or protic acids (entry 12) afforded substantially lower
yields of 2a. Likewise, the performance of the process at distinct
temperatures did not improve the reaction outcome.19
Having established an optimal system for the selective Pd-
catalyzed ortho-halogenation of “click compounds”, we next
evaluated its generality utilizing a variety of substituted 4-aryl-
1,2,3-triazoles easily obtained by CuAAC of the corresponding
alkynes and azides. Importantly, the electronic nature of the arene
had a tremendous impact on the halogenation process. The Pd-
catalyzed ortho-bromination of triazole derivatives bearing either
electron-neutral or electron-withdrawing substituents smoothly
proceeded to selectively afford the corresponding monobromi-
nated arenes in moderate to good yields (Scheme 2). When the
parent N-chloro- and N-iodosuccinimide were used, the
corresponding chlorinated and iodinated products, 2b and 2c,
respectively, were obtained, albeit in comparatively lower yields.
Importantly, meta-substituted arenes demonstrated excellent site
selectivity in the process, providing monohalogenated com-
pounds as sole regioisomers (2a−j,p−q) as verified by X-ray
analysis of 2q. The efficiency of the reaction was not impeded by
used.
ortho substituents on the aryl ring (2k−o,u,v). Of remarkable
importance are examples 2r−t where arenes with various
accessible C(sp2)−H bonds selectively underwent the mono-
bromination event and not even traces of dihalogenated product
were detected. Notably, several functional groups were perfectly
accommodated such as ethers (2i), halides (2k−q,t−v), cyanides
(2j,s), and tosylate (2w). Our process was also applicable to 4-
benzyl-1,2,3-triazoles 1w,x proceeding in those cases through the
presumable formation of a six-membered palladacycle.
In striking contrast, when the electron-rich substrate 3a was
submitted to the standard conditions, the projected triazole-
directed ortho-bromination did not occur in the presence or
absence of palladium catalyst, and instead, the bromination
selectively took place in the 5-position of naphthyl ring (Scheme
3). After slight modifications of the reaction conditions, we
observed that simply mixing the substrate with NBS at room
temperature furnished brominated product 4a in 88% yield.
Interestingly, other electron-rich substrates followed the same
trend, and uncatalyzed EAS predominated over the Pd-catalyzed
ortho-functionalization process. In this respect, triazoles bearing
acetanilide and anisole units (3b,c) as well as thiophenes (3e,f)
were efficiently brominated following an EAS mechanism.20
Importantly, the alternative employment of N-clorosuccinimide
ledtothecorrespondingchlorinatedproduct4dinexcellentyield.
The usefulness of the developed method is highlighted by the
synthetically practical transformations that the prepared triazoles
can undergo at the C−Br site through metal-catalyzed C−C and
C−N bond-forming processes. As depicted in Scheme 4, Pd-
catalyzed Sonogashira and Suzuki couplings provided 5a and 5b
in good yields, and the latter can be also obtained upon nickel
catalysis albeit in moderate yields (see the Supporting
Information). Note that common scaffolds in medicinally
relevant targets such as heterocyclic arenes were successfully
introduced by Cu-catalyzed N-arylations that furnished 5c and 5d
in excellent yields.
B
DOI: 10.1021/acs.orglett.7b00275
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a b
,
Scheme 3. Regioselective EAS of Arenes 3a−f
Table 2. Control Experiments with Triazole 1s
a
b
As for Table 1, entry 1. Yield of isolated product after column
chromatography, average of at least two independent runs.
a
Reaction conditions: 3 (0.25 mmol), NXS (1.5 equiv), DCE (0.25
Scheme 5. Proposed Reaction Mechanism
b
M) at rt for 24 h under Ar. Yield of isolated product after column
chromatography, average of at least two independent runs. Using N-
bromosuccinimide. Using N-chlorosuccinimide.
c
d
Scheme 4. Versatility of Brominated Triazoles
DFT studies to be more stable than its monomeric species IA.22
Therefore, adissociationpriortotheoxidationstepseemsarather
feasible reaction pathway. Likewise, in accordance with experi-
ments depicted on Table 2, DFT studies revealed that the
oxidation step is energetically more favorably assisted by in situ
generated PivOBr (path a) than NBS (path b).22,23 Finally, C−Br
bond-forming reductive elimination24 from the monometallic Pd
intermediate II would afford the desired product and regenerate
the active Pd catalyst.18
In order to gain some insights into the reaction mechanism,
several control experiments as well as DFT studies were
performed. To support the intermediacy of a triazole-containing
palladacycle, a stoichiometric reaction of triazole 1s with
Pd(OAc)2 in DCE was performed and the bimetallic complex A
was pleasingly obtained in 93% yield. Such a dinuclear complex
was characterized by NMR spectroscopy and by X-ray
crystallography; to the best of our knowledge, it represents the
first palladallacycle involving a “click” 1,2,3-triazole as chelating
group. Importantly, complex A efficiently catalyzed the formation
of 2s from 1s in 87% isolated yield, which indicates that it is likely
an active species within the catalytic cycle (Table 2, entry 2). In
related metal-catalyzed halogenations, the crucial role of the acid
as additive has been described as either to protonate the carbonyl
group of the N-halosuccinimide, thus rendering a more effective
halonium source,6f or to in situ produce the corresponding acyl
hypohalite by combination with NXS.7d Accordingly, we
prepared a solution of pivaloyl hypobromite (PivOBr) following
a reported procedure,21 and it was found to be a powerful
halogenating agent providing the brominated arene 2s in yields
similar to those under the standard conditions (Table 2, entry 3)
or in moderate yield when complex A was used as the Pd source
(Table 2, entry 5).
In summary, we have disclosed unprecedented C(sp2)−H
halogenations events upon “click” triazoles, which represent
practical late-stage diversification strategies toward molecular
complexity. The electronic nature of the arene is pivotal in
selectively boosting the reaction mechanism either by a triazole-
directed Pd-catalyzed ortho-functionalization or by an EAS
reaction. Importantly, a triazole-containing palladacycle was
identified as a competent intermediate along the catalytic cycle,
andDFTstudiessupported theroleofinsitugenerated PivOBras
the more plausible halogenating agent. Further mechanistic
investigations are currently underway in our laboratories.
ASSOCIATED CONTENT
* Supporting Information
■
S
TheSupportingInformationisavailablefreeofchargeontheACS
Publications website at DOI: 10.1021/acs.orglett.7b00275.
Experimental procedures, DFT calculation data, X-ray
crystallographic data for compound 2q and complex A, and
spectral data (PDF)
X-ray crystallographic data for compound 2q (CIF)
X-ray crystallographic data for complex A (CIF)
While further studies are clearly required to confirm the
mechanistic scenario, a plausible mechanism is proposed in
Scheme5.Thereactionwouldbeginbyacyclopalladationprocess
to furnish a bimetallic species IB which has been confirmed by
C
DOI: 10.1021/acs.orglett.7b00275
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
9739. (e)Gu, Q.;AlMamari, H. H.;Graczyk, K.;Diers, E.;Ackermann, L.
Angew. Chem., Int. Ed. 2014, 53, 3868. (f) Ye, X.; Shi, X. Org. Lett. 2014,
16, 4448. (g) Ye, X.; He, Z.; Ahmed, T.; Weise, K.; Akhmedov, N. G.;
Petersen, J. L.; Shi, X. Chem. Sci. 2013, 4, 3712.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: arkaitz.correa@ehu.es.
ORCID
(11)Forreviews, see:(a)Wei, F.;Wang, W.;Ma, Y.;Tung, C.-H.;Xu, Z.
́ ́
Chem. Commun. 2016, 52, 14188. (b) Haldon, E.; Nicasio, M. C.; Perez,
Arkaitz Correa: 0000-0002-9004-3842
Notes
P. J. Org. Biomol. Chem. 2015, 13, 9528. (c) Ackermann, L.;Potukuchi, H.
K. Org. Biomol. Chem. 2010, 8, 4503. (d) Meldal, M.; Tornøe, C. W.
Chem. Rev. 2008, 108, 2952.
The authors declare no competing financial interest.
(12) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed.
2001, 40, 2004.
ACKNOWLEDGMENTS
(13) For selected examples, see: (a) Qureshi, Z.; Kim, J. Y.; Bruun, T.;
Lam, H.; Lautens, M. ACS Catal. 2016, 6, 4946. (b) Tian, X.; Yang, F.;
Rasina, D.; Bauer, M.; Warratz, S.; Ferlin, F.; Vaccaro, L.; Ackermann, L.
Chem. Commun. 2016, 52, 9777. (c) Ackermann, L.; Althammer, A.;
Fenner, S. Angew. Chem., Int. Ed. 2009, 48, 201. (d) Ackermann, L.;
Vicente, R.;Born, R. Adv. Synth. Catal. 2008, 350, 741. (e)Chuprakov, S.;
Chernyak, N.; Dudnik, A. S.; Gevorgyan, V. Org. Lett. 2007, 9, 2333.
(f) Iwasaki, M.; Yorimitsu, H.; Oshima, K. Chem. - Asian J. 2007, 2, 1430.
(14)(a)Jiang, Y.;Ma, X.;Zhao, F.;Han, C. Synlett2016, DOI:10.1055/
■
We thank SGIker of UPV/EHU for technical support and
acknowledge European funding (ERDF and ESF). We are
grateful to Gobierno Vasco (ELKARTEK_KK-2015/0000101;
IT_1033-16) and the UPV/EHU (GIU15/31) for financial
support. A.C. thanks MINECO for a Ramon y Cajal research
́
contract (RYC-2012-09873). Cost-CHAOS action is also
acknowledged.
́
s-0036-1588123. (b) Ackermann, L.; Novak, P.; Vicente, R.; Pirovano,
V.; Potukuchi, H. Synthesis 2010, 13, 2245. (c) Ackermann, L.; Vicente,
R.; Althammer, A. Org. Lett. 2008, 10, 2299. (d) Ackermann, L.; Born, R.;
Vicente, R. ChemSusChem 2009, 2, 546. For related alkenylations, see:
(e) Tirler, C.; Ackermann, L. Tetrahedron 2015, 71, 4543.
(15) (a) Irastorza, A.; Aizpurua, J. M.; Correa, A. Org. Lett. 2016, 18,
1080. (b)Zhao, F.;Chen, Z.;Ma, X.;Huang, S.;Jiang,Y. TetrahedronLett.
2017, 58, 614. (c) Zhao, F.; Chen, Z.; Huang, S.; Jiang, Y. Synthesis 2016,
48, 2105.
REFERENCES
■
(1) (a) Saikia, I.; Borah, A. J.; Phukan, P. Chem. Rev. 2016, 116, 6837.
(b) Petrone, D. A.; Ye, J.; Lautens, M. Chem. Rev. 2016, 116, 8003.
(2) Ruiz-Castillo, P.; Buchwald, S. L. Chem. Rev. 2016, 116, 12564 and
references cited therein.
(3) De la Mare, P. B. Electrophilic Halogenations; Cambridge University
Press: Cambridge, 1976; Chapter 5.
(4) Hodgson, H. H. Chem. Rev. 1947, 40, 251.
(16) Correa, A.; Fiser, B.; Gom
13365.
́
ez-Bengoa, E. Chem. Commun. 2015, 51,
(5) (a) Florio, S.; Salomone, A. Synthesis 2016, 48, 1993. (b) Hartung,
C. G.; Snieckus, V. In Modern Arene Chemistry; D., Astruc, Eds.; Wiley-
VCH: Weinheim, 2002; p 330.
(17) For halogenations of 2-aryl-1,2,3-triazoles, see: Tian, Q.; Chen, X.;
Liu, W.; Wang, Z.; Shi, S.; Kuang, C. Org. Biomol. Chem. 2013, 11, 7830.
The bromination of related 1-aryl-1,2,3-triazoles was reportedly
unsuccessful. Remarkably, our model substrate 1a also remained
unreactive under those conditions, thus evidencing the crucial impact
of the triazole substitution pattern in its metal-coordinating ability and
the subtleties of “click triazoles”.
(18) Although the exact role of PhI(OAc)2 is currently unclear, it
presumably helps to maintain the reactive Pd species. See ref 6b,c. At this
stage, the in situ formation of highly electrophilic PhIBr2 upon ligand
exchange with NBS cannot be entirely ruled out. Karade, N. N.;
Shirodkar, S. G.; Dhoot, B. M.; Waghmare, P. B. J. Chem. Res. 2005, 2005,
274.
(19) The addition of diamines or protected amino acids as supporting
ligands did not improve the yields. See, for example: Engle, K. A. Pure
Appl. Chem. 2016, 88, 119.
(20) For selected electrophilic halogenations of electron-rich arenes,
see: (a) Maddox, S. M.; Dinh, A. N.; Armenta, F.; Um, J.; Gustafson, J. L.
Org. Lett. 2016, 18, 5476. (b) Prakash, G. K. S.; Mathew, T.; Hoole, D.;
Esteves, P. M.; Wang, Q.; Rasul, G.; Olah, G. A. J. Am. Chem. Soc. 2004,
126, 15770. (c) Yang, L.; Lu, Z.; Stahl, S. S. Chem. Commun. 2009, 6460.
(d) Bedford, R. B.; Mitchell, C. J.; Webster, R. L. Chem. Commun. 2010,
46, 3095.
(21) (a) Chen, K.; Baran, P. S. Nature 2009, 459, 824. (b) Skell, P. S.;
May, D. D. J. Am. Chem. Soc. 1983, 105, 3999.
(22) For a full discussion based on DFT studies, see the Supporting
Information.
(23) For reviews, see: (a) Topczewski, J. J.; Sanford, M. S. Chem. Sci.
2015, 6, 70. (b) Powers, D. C.; Ritter, T. Acc. Chem. Res. 2012, 45, 840.
(c) Hickman, A. J.; Sanford, M. S. Nature 2012, 484, 177.
(24) (a) Racowski, J. M.; Sanford, M. S. Top. Organomet. Chem. 2011,
35, 61. (b)Powers, D. C.;Benitez, D.;Tkatchouk, E.;Goddard, W. A., III;
Ritter, T. J. Am. Chem. Soc. 2010, 132, 14092.
(6) For selected Pd-catalyzed C(sp2)−H halogenations, see: (a) Sun,
X.; Yao, X.; Zhang, C.; Rao, Y. Chem. Commun. 2015, 51, 10014.
(b) Sarkar, D.; Melkonyan, F. S.; Gulevich, A. V.; Gevorgyan, V. Angew.
Chem., Int. Ed. 2013, 52, 10800. (c) Sun, X.; Shan, G.; Sun, Y.; Rao, Y.
Angew. Chem., Int. Ed. 2013, 52, 4440. (d) Wang, X.-C.; Hu, Y.;
Bonacorsi, S.; Hong, Y.; Burrell, R.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135,
10326. (e) Du, B.; Jiang, X.; Sun, P. J. Org. Chem. 2013, 78, 2786.
(f) Huang, C.; Chernyak, N.; Dudnik, A. S.; Gevorgyan, V. Adv. Synth.
Catal. 2011, 353, 1285. (g)Bedford, R. B.;Haddow, M. F.;Mitchell, C. J.;
Webster, R. L. Angew. Chem., Int. Ed. 2011, 50, 5524. (h) Mei, T.-S.; Giri,
R.; Maugel, N.; Yu, J.-Q. Angew. Chem., Int. Ed. 2008, 47, 5215. (i) Wan,
X.; Ma, Z.; Li, B.; Zhang, K.; Cao, S.; Zhang, S.; Shi, Z. J. Am. Chem. Soc.
2006, 128, 7416. (j) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford, M. S.
Org. Lett. 2006, 8, 2523.
(7) For selected C(sp2)−H halogenations using other transition-metal
catalysts, see: (a) Zhan, B.-B.; Liu, Y.-H.; Hu, F.; Shi, B.-F. Chem.
Commun. 2016, 52, 4934. (b) Li, B.; Liu, B.; Shi, B.-F. Chem. Commun.
́
2015, 51, 5093. (c) Urones, B.; Martínez, A. M.; Rodríguez, N.; Arrayas,
R. G.; Carretero, J. C. Chem. Commun. 2013, 49, 11044. (d) Du, Z.-J.;
Gao, L.-X.; Lin, Y.-J.; Han, F.-S. ChemCatChem 2014, 6, 123.
(8) For selected reviews on chelation-assisted C−H functionalizations,
see: (a) Zhu, R.-Y.; Farmer, M. E.; Chen, Y.-Q.; Yu, J.-Q. Angew. Chem.,
Int. Ed. 2016, 55, 10578. (b) Liu, J.; Chen, G.; Tan, Z. Adv. Synth. Catal.
2016, 358, 1174. (c) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem.
Rev. 2012, 112, 5879. (d) Daugulis, O.; Roane, J.; Tran, L. D. Acc. Chem.
Res. 2015, 48, 1053. (e) Rouquet, G.; Chatani, N. Angew. Chem., Int. Ed.
2013, 52, 11726. (f) Ackermann, L. Chem. Rev. 2011, 111, 1315.
(g) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147.
(9) For selected reviews, see: (a) Kacprzak, K.; Skiera, I.; Piasecka, M.;
Paryzek, Z. Chem. Rev. 2016, 116, 5689. (b) Tiwari, V. K.; Mishra, B. B.;
Mishra, K. B.; Mishra, N.; Singh, A. S.; Chen, X. Chem. Rev. 2016, 116,
3086.
(10) (a) Cera, G.; Ackermann, L. Top. Curr. Chem. 2016,
DOI: 10.1007/s41061-016-0059-6. (b) Ye, X.; Xu, C.; Wojtas, L.;
Akhmedov, N. G.; Chen, H.; Shi, X. Org. Lett. 2016, 18, 2970. (c) Cera,
G.; Haven, T.; Ackermann, L. Angew. Chem., Int. Ed. 2016, 55, 1484.
(d) Al Mamari, H. H.; Diers, E.; Ackermann, L. Chem. - Eur. J. 2014, 20,
D
DOI: 10.1021/acs.orglett.7b00275
Org. Lett. XXXX, XXX, XXX−XXX