Metal-free C-H amination for indole synthesis

Article abstract of DOI:10.1021/ol5015398

An effective metal-free C-H amination of N-Ts-2-alkenylanilines by using DDQ as an oxidant has been developed to afford a diverse range of substituted indoles. This protocol is operationally simple and robust, obviates the need of expensive transition-metal catalysts, and offers a broad substrate scope. A mechanism involving a radical cation generated by SET and a migratorial process via a phenonium ion intermediate is proposed.

Full text of DOI:10.1021/ol5015398

Letter
pubs.acs.org/OrgLett
Metal-Free C−H Amination for Indole Synthesis
Young Ho Jang and So Won Youn*
Center for New Directions in Organic Synthesis, Department of Chemistry and Research Institute for Natural Sciences, Hanyang
University, Seoul 133-791, Korea
S
* Supporting Information
ABSTRACT: An effective metal-free C−H amination of N-Ts-2-alkenylanilines by
using DDQ as an oxidant has been developed to afford a diverse range of substituted
indoles. This protocol is operationally simple and robust, obviates the need of
expensive transition-metal catalysts, and offers a broad substrate scope. A mechanism
involving a radical cation generated by SET and a migratorial process via a
phenonium ion intermediate is proposed.
ue to their ubiquity in nature and broad application in
chemistry, biology, and material sciences, indoles are one
Scheme 1. Indole Synthesis from 2-Alkenylanilines
D
of the most important and valuable heterocycles.1 Consequently,
numerous methods for the synthesis of indole derivatives have
been developed,2 and new, more efficient synthetic strategies still
continue to be pursued. C−H amination of 2-alkenylanilines is
one of the straightforward methods for the construction of an
indole moiety. Two different approaches have been developed
for such a purpose: via (1) Pd(II) catalysis and (2) nitrogen
radical (cation). Since pioneered by Hegedus and co-workers,
Pd(II)-catalyzed aminopalladation has evolved as one of the
most efficient methods for the synthesis of indoles, albeit with
very limited substrate scope (Scheme 1a).3 Recently, our group
showed a single example, synthesis of 2-phenylindole, as a vinylic
C−H bond activation variant in a Pd-catalyzed oxidative C−H
amination of N-Ts-2-arylanilines for the synthesis of carbazo-
les.3g In contrast, a radical mechanism has also been implicated in
the reactions of the same substrates (Scheme 1b).4 Very recently,
Chemler’s group showed a few examples of a Cu-catalyzed
intramolecular oxidative amination of alkenes for the synthesis of
indoles, suggesting a mechanism involving nitrogen-radical
addition to the alkenes.4a In addition, Zheng and co-workers
reported a photocatalytic synthesis of indoles involving a
nitrogen-centered radical cation generated from N-p-alkoxy-
phenyl-2-alkenylanilines.4b Despite the significant advance with
respect to the substrate scope, the requirement of a p-
alkoxyphenyl group on the nitrogen atom, which could facilitate
the generation of a nitrogen radical cation, could limit this
practicality due to its difficult removal (R = 4-MeOC6H4,
4-nBuOC6H4).
related methods (Scheme 1a,b),3,4 the reaction protocol
described herein significantly improved the efficiency and
practicality of indole formation via C−H amination of 2-
alkenylanilines, overcoming the deficiencies with regard to
substrate scope3,4a and N-protecting group.4b
We began our studies using 1a as the test substrate and
examined the reaction parameters to identify optimal conditions
(Table 1). Gratifyingly, it was found that DDQ promoted this
C−H amination reaction to afford 2a in 69% yield (entry 1).
Various solvents were examined, and CCl4 appeared preferable
In view of the versatility and importance of indoles, we were
interested in developing a new, efficient synthetic protocol for
the C−H amination of 2-alkenylanilines. Herein we disclose a
highly effective, metal-free C−H amination of 2-alkenylanilines
(Scheme 1c). The use of DDQ (2,3-dichloro-5,6-dicyanobenzo-
quinone)5 allowed the easy preparation of a diverse array of
substituted indoles. In sharp contrast to the previously reported,
Received: May 29, 2014
© XXXX American Chemical Society
A
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Organic Letters
Letter
Table 1. Optimization Studies
Table 2. Substrate Scope: Mono- or Disubstituted Alkene
Derivatives
a
entry
oxidant
DDQ
solvent
time (h) yield (%)
1
ClCH2CH2Cl
CCl4
24
7
69
time
(h)
a
2
DDQ
(96)
(96)
87
entry
1
R1
R2
R3
R4
Ph (1a)
yield (%)
3
DDQ
CH3CCl3
toluene
c-hexane
1,4-dioxane
MeCN
DMF
24
24
24
24
24
24
24
24
2
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Ph
H
H
H
H
H
H
H
H
H
24
24
0.5
16
16
2
96 (2a)
76 (2a)
42 (2b)
84 (2c)
90 (2d)
4
DDQ
bc
,
2
3
4
5
6
7
8
9
H
H
Ph ((Z)-1a)
4-MeC6H4 (1b)
3-MeC6H4 (1c)
2-MeC6H4 (1d)
4-MeOC6H4 (1e)
3-MeOC6H4 (1f)
4-ClC6H4 (1g)
4-NO2C6H4 (1h)
3-CF3C6H4 (1i)
1-naphthyl (1j)
3-thienyl (1k)
H (1l)
b
5
DDQ
90
c
H
H
6
DDQ
69
40
6
H
H
7
DDQ
H
H
8
DDQ
d
H
H
99 (2e)
74 (2f)
86 (2g)
9
DDQ
iPrOH
−
−
8
H
H
10
12
24
18
10
5
10
11
MnO2
Mn(OAc)3·2H2O
PhI(OAc)2
FeCl3
CCl4
H
H
CCl4
H
H
73 (2h)
94 (2i)
99 (2j)
86 (2k)
50 (2l)
95 (2m)
57 (2n)
6 (2o)
c
12
CCl4
13
24
24
2
−
−
7
c
10
11
12
13
14
15
16
17
18
19
20
21
22
23
H
H
d
13
14
15
CCl4
H
H
CuBr2
I2
CCl4
H
H
d
CCl4
41
c
c
H
H
5
e
16
DDQ
CH3CCl3
CH3CCl3
CH3CCl3
CH3CCl3
24
24
21
24
57
H
H
H (1m)
21
2
f
17
DDQ
(85)
62
H
OMe
Me
Cl
NO2
H
Ph (1n)
g
18
DDQ
H
Ph (1o)
24
9
h
19
DDQ
90−91
H
Ph (1p)
87 (2p)
100 (2q)
100 (2r)
20 (2s)
86 (2t)
99 (2u)
96 (2v)
a
1
Yields were determined by H NMR using trichloroethylene as an
H
Ph (1q)
24
2
internal standard. Value in parentheses indicates an isolated yield.
OMe
Me
Cl
CF3
NO2
Ph (1r)
b
Mixture of 2- and 3-phenyl-substituted N-Ts-indoles was obtained (2-
c
H
Ph (1s)
19
24
24
22
c
d
Ph:3-Ph = 9:1). At 25 °C. N-Ts-2-Phenylindoline was obtained in
17−21%. Using 1 equiv DDQ. At 100 °C. In the presence of 1 equiv
LiOMe. In the presence of 1 equiv Na2CO3 or K2CO3.
e
f
g
H
Ph (1t)
h
H
Ph (1u)
H
Ph (1v)
a
b
c
Isolated yield. Z-Isomer of 1a was used as a substrate. Performed at
d
with regard to reaction time and product yield (entries 1−9).
Due to toxicity and safety issues, however, 1,1,1-trichloroethane
(CH3CCl3) was selected as the solvent of choice, albeit requiring
a little longer reaction time than in CCl4 (entry 2 vs entry 3).
Among a variety of oxidants examined, DDQ was revealed as the
most effective oxidant for this transformation (entries 10−15).
Reducing either the reaction temperature or the amount of DDQ
led to a lower yield of 2a (entries 16 and 17). We further
hypothesized that the introduction of a base could either enhance
the nucleophilicitiy of sulfonamide or facilitate the generation of
nitrogen radical, thereby increasing the rate of the oxidative
cyclization. However, addition of LiOMe was detrimental, while
both Na2CO3 and K2CO3 gave no beneficial effect (entries 18
and 19).
With the optimized conditions in hand, we explored the effect
of protecting groups.6 Considering the susceptibility of 2-
alkenylanilines to oxidation at both nitrogen atom and olefin
moiety, judicious selection of an N-protecting group would be
crucial to the success of this oxidative cyclization reaction. As
expected, electron density on nitrogen atom exerted a great
influence on the reaction outcome, and the effectiveness of the
sulfonyl protecting group was immediately apparent. Among
sulfonyl groups, the Ts (p-toluenesulfonyl) group proved the
superior as a protecting group for this reaction, giving a delicately
balanced nucleophilicity and oxidation susceptibility of the NH
group.
150 °C. Mixture of 2- and 3-aryl-substituted N-Ts-indoles was
obtained (2-:3- = 5.6:1).
(entries 1−10). The reactions of (Z)-isomer also proceeded
uneventfully to form 2a in 76% yield (entry 2). Both naphthyl-
and heteroaryl-substituted alkenes were well tolerated for this
reaction (entries 11 and 12). Noteworthy is the fact that the
reaction of 1e bearing an electron-rich substituent (R4 = 4-
MeOC6H4) afforded the mixture of 2- and 3-substituted indole
products (2-:3- = 5.6:1, entry 6), indicating that a migratorial
process occurred via a carbocation intermediate (vide infra).7
Mono- and 1,1-disubstituted terminal alkenes (R3 = H or Ph, R4
= H) proved to be suitable substrates (entries 13 and 14). In
some cases, interestingly, a few substrates among Me-substituted
ones led to complicated mixtures along with the desired products
in low yields (entries 3, 16, and 20), probably resulting from the
oxidation of the benzylic position (i.e., Me group) by DDQ.8
Subsequently, we also investigated the effects of substituents
(R1, R2) residing on the aromatic moiety of N-Ts-2-styrylanilines
(entries 15−23). Both electron-donating and -withdrawing
substituents were well tolerated with the exception of Me
group as mentioned above. An electron-donating substituent
(e.g., OMe) para to both amino moiety (R1) and alkene moiety
(R2) accelerated the reaction rate considerably, presumably as a
consequence of the increased nucleophilicity of amine and the
reduced oxidation potential of alkene (possibly amine as well),
respectively (entries 15 and 19). The latter observation is also
consistent with the effect of a 4-MeO-phenyl substituent at the
alkene moiety (R4 = 4-MeOC6H4, entry 6). In sharp contrast,
reducing the electron density of olefin through the direct
introduction of electron-withdrawing substituents (e.g., R4 =
We proceeded to explore the substituent effect at the alkene
moiety (Table 2). A variety of N-Ts-2-styrylanilines (R4 = aryl)
underwent C−H amination smoothly to afford the correspond-
ing indoles in good to excellent yields irrespective of the aryl
substitution, showing little electronic and/or steric dependence
B
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Organic Letters
Letter
CO2nBu, CONMe2, CN, PO(OEt)2) at the alkene moiety gave
an adverse effect, leading to no reaction with mostly recovered
starting materials (not shown). In the case of an alkyl-substituent
bearing substrate (R4 = alkyl) such as 1w, dihydroquinoline 2w′
instead of indole was obtained as a sole isolable product in a
modest yield (eq 1), suggesting a mechanism involving an olefin
Scheme 2. Proposed Mechanism
radical cation, followed by hydrogen atom transfer to generate
the allyl cation.5,6,9 This is in sharp contrast to the result of
Zheng’s work in which not dihydroquinoline 2w′ but the
corresponding indole product was obtained through electro-
philic addition of a nitrogen-centered radical cation to a tethered
alkene.4b On the other hand, smooth deprotection of the Ts
group secured the production of NH free indole 3 in good yield
(eq 2).
With the speculated carbocation intermediate in mind, we next
investigated the reaction of β,β-disubstituted 2-alkenylanilines
(4) under the standard reaction conditions. As shown in Table 3,
these reactions proceeded uneventfully to generate the
corresponding 2,3-disubstituted indoles, showing higher mi-
gratory aptitude of an aryl group than an alkyl group (entries 1
and 2). In general, electron-rich aryl groups migrated
preferentially (entries 3−8), supporting that cationic rearrange-
ments took place through the formation of phenonium ion
intermediate (D, Scheme 2).7 Similarly to the outcome from 1w
in eq 1, dihydroquinoline 5aB was obtained along with indole
5aA resulted from a phenyl migration in the reaction of 4a (entry
1),5,9 while the formation of the corresponding dihydroquinoline
was not observed in the reaction of 4b (entry 2). In sharp
contrast to the reaction of 1b (Table 2, entry 3), interestingly, a p-
tolyl substituent was well tolerated in the reaction of 4d (Table 3,
entry 4).
To gain insight into this reaction, a series of control
experiments were performed.6 Radical clock experiments using
1x and 1y were conducted under the optimized conditions and
gave very different outcomes (eq 3).10 The first afforded 2x as the
Table 3. Oxidative Cyclization Reactions of Trisubstituted
Alkene Derivatives Involving 1,2-Aryl Migration
sole product of which cyclopropyl ring remained intact,
presumably because a ring opening reaction of the cyclopropyl
benzyl radical is slower than its competitive oxidation to benzylic
cation (B → C, Scheme 2).4b,10c In sharp contrast, the latter using
1y, in which a phenyl group would allow for a fast ring cleavage to
result in a benzyl radical,10b led to a complicated mixture and 2y′
could be isolated, albeit in a low yield. This product is likely to be
formed through a cyclopropane ring opening, suggesting that a
carbon radical intermediate was involved during the reaction.
Inclusion of BHT (3,5-di-tert-butyl-4-hydroxytoluene) or
TEMPO (2,2,6,6-tetramethylpiperidine-N-oxyl) as an additive
had deleterious effect on the efficiency of the indole formation,
while the corresponding trapping products were not observed in
both cases.6 When DDQ was added to a solution of stilbene, we
observed the immediate color change to deep green, whereas a
solution of 6 turned to brown by the addition of DDQ.
Apparently, a radical ion pair complex might be generated
through a single-electron transfer process between the stilbene
double bond and DDQ.6 In stark contrast to the Chemler’s work
wherein C−H amination products such as 9 were formed
through nitrogen-radical addition to various radical acceptors
(e.g., 7),4a an intermolecular variant of our protocol did not
proceed, giving fully recovered 6 and a byproduct 8 derived from
7 and DDQ (eq 4). The introduction of a radical acceptor 7 to
Reaction conditions: Substrate (1 equiv) and DDQ (2 equiv) in
a
b
1
CH3CCl3 (0.1 M) at 120 °C. Isolated yield. Determined by H
c
NMR. Starting materials were recovered (4b: 12%, 4f: 20%, 4g: 68%).
d
Performed at 150 °C.
C
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Organic Letters
Letter
Hierso, J.-C. Chem. Soc. Rev. 2012, 41, 3929. (d) Cacchi, S.; Fabrizi, G.
Chem. Rev. 2011, 111, PR215. (e) Taber, D. F.; Tirunahari, P. K.
Tetrahedron 2011, 67, 7195. (f) Bandini, M.; Eichholzer, A. Angew.
Chem., Int. Ed. 2009, 48, 9608. (g) Humphrey, G. R.; Kuethe, J. T. Chem.
Rev. 2006, 106, 2875. (h) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1
2000, 1045. (i) Hegedus, L. S. Angew. Chem., Int. Ed. 1988, 27, 1113.
(3) (a) Hegedus, L. S.; Allen, G. F.; Bozell, J. J.; Waterman, E. L. J. Am.
Chem. Soc. 1978, 100, 5800. (b) Harrington, P. J.; Hegedus, L. S. J. Org.
Chem. 1984, 49, 2657. (c) Harrington, P. J.; Hegedus, L. S.; McDaniel,
K. F. J. Am. Chem. Soc. 1987, 109, 4335. (d) Krolski, M. E.; Renaldo, A.
F.; Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1988, 53, 1170. (e) Larock, R.
C.; Hightower, T. R.; Hasvold, L. A.; Peterson, K. P. J. Org. Chem. 1996,
61, 3584. (f) Tsvelikhovsky, D.; Buchwald, S. L. J. Am. Chem. Soc. 2010,
132, 14048. (g) Youn, S. W.; Bihn, J. H.; Kim, B. S. Org. Lett. 2011, 13,
3738.
our standard reaction conditions using 1a as the substrate
afforded 2a and the same byproduct 8 as in eq 4 without 10,
which could be formed through interception of a radical
intermediate by alkene 7 in domino C−H amination/
intermolecular Heck-type coupling reaction (eq 5).11
While a clear mechanistic picture is elusive at this juncture,
these findings suggest that oxidation of the carbon radical (B,
Scheme 2), resulted from the intramolecular nucleophilic attack
by the o-sulfonamide group toward an olefin radical cation (via
A),12 to the corresponding benzylic carbocation intermediate
(C) followed by the deprotonation (B → C → 2) is much faster
than intermolecular addition of the radical (B) to an alkene (e.g.,
7). In addition, intermolecular C−N and C−C bond formations
under our conditions appear to be unfavorable.
(4) (a) Liwosz, T. W.; Chemler, S. R. Chem.Eur. J. 2013, 19, 12771.
(b) Maity, S.; Zheng, N. Angew. Chem., Int. Ed. 2012, 51, 9562.
(5) For examples on DDQ-mediated oxidation of olefins and
dehydrogenative cross-coupling reaction for C−C and C−heteroatom
bond formations, see: (a) Bhattacharya, A.; DiMichele, L. M.; Dolling,
U.-H.; Grabowski, E. J. J.; Grenda, V. J. J. Org. Chem. 1989, 54, 6118.
(b) Rathore, R.; Kochi, J. K. Tetrahedron Lett. 1994, 35, 8577. (c) Cheng,
D.; Bao, W. L. Adv. Synth. Catal. 2008, 350, 1263. (d) Li, Y.; Bao, W. L.
Adv. Synth. Catal. 2009, 351, 865. (e) Mo, H. J.; Bao, W. L. Adv. Synth.
Catal. 2009, 351, 2845. (f) Jin, J.; Li, Y.; Wang, Z. J.; Qian, W. X.; Bao, W.
L. Eur. J. Org. Chem. 2010, 1235. (g) Wang, Z.; Mo, H.; Cheng, D.; Bao,
W. Org. Biomol. Chem. 2012, 10, 4249. (h) Wu, aY.; Kwong, F. Y.; Li, P.;
Chan, A. S. C. Synlett 2013, 2009.
In summary, we have developed an effective metal-free C−H
amination of N-Ts-2-alkenylanilines by using DDQ as an
oxidant. This new protocol represents an attractive route for a
straightforward access to a diverse range of substituted indoles, a
privileged motif found in a number of natural and designed
compounds with important biological and physical implications.
Our experimental findings suggest that this oxidative cyclization
reaction implicates a radical cation generated by SET and a
phenonium ion intermediate for a subsequent migratorial
process, following a postulated mechanistic route as depicted
in Scheme 2.
Despite its potential utility and efficiency in indole synthesis,
the narrow substrate scope of C−H amination of 2-alkenylani-
lines seems to have encumbered its application in organic
synthesis.3,4 The reaction presented herein could overcome the
longstanding deficiencies and, furthermore, offer high efficiency
and facilitation as well as a broad substrate scope without using
expensive transition-metal catalysts and a special equipment/
experimental setup. Further investigations to extend to an
intermolecular version of this protocol together with detailed
mechanistic studies are currently underway in our laboratory.
(6) For details, see Supporting Information.
(7) Selected recent examples, see: (a) del Río, E.; Menen
́
dez, M. I.;
Lopez, R.; Sordo, T. L. J. Am. Chem. Soc. 2001, 123, 5064. (b) Boye, A.
́
C.; Meyer, D.; Ingison, C. K.; French, A. N.; Wirth, T. Org. Lett. 2003, 5,
2157. (c) Shen, M.; Leslie, B. E.; Driver, T. G. Angew. Chem., Int. Ed.
2008, 47, 5056. (d) Manet, I.; Monti, S.; Grabner, G.; Protti, S.; Dondi,
D.; Dichiarante, V.; Fagnoni, M.; Albini, A. Chem.Eur. J. 2008, 14,
1029. (e) Shahzad, S. A.; Vivant, C.; Wirth, T. Org. Lett. 2010, 12, 1364.
(f) Sun, K.; Liu, S.; Bec, P. M.; Driver, T. G. Angew. Chem., Int. Ed. 2011,
50, 1702. (g) Stokes, B. J.; Liu, S.; Driver, T. G. J. Am. Chem. Soc. 2011,
133, 4702. (h) Singh, F. V.; Rehbein, J.; Wirth, T. ChemistryOpen 2012,
1, 245. (i) Jones, C.; Nguyen, Q.; Driver, T. G. Angew. Chem., Int. Ed.
2014, 53, 785 and ref 4b.
ASSOCIATED CONTENT
* Supporting Information
■
S
(8) Reviews: (a) Walker, D.; Hiebert, J. D. Chem. Rev. 1967, 67, 153.
(b) Fu, P. P.; Harvey, R. G. Chem. Rev. 1978, 78, 317. Selected
examples: (c) Merlini, L.; Cardillo, G.; Cricchio, R. Tetrahedron 1971,
27, 1875. (d) Lee, H.; Harvey, R. G. J. Org. Chem. 1988, 53, 4587.
(e) Temme, O.; Frohlich, R.; Laschat, S. J. Prakt. Chem. 1998, 340, 341.
(f) Utley, J. H. P.; Rozenberg, G. G. Tetrahedron 2002, 58, 5251.
(g) Barton, B.; Logie, C. G.; Schoonees, B. M.; Zeelie, B. Org. Process Res.
Dev. 2005, 9, 62. (h) Batista, V. S.; Crabtree, R. H.; Konezny, S. J.; Luca,
O. R.; Praetorius, J. M. New J. Chem. 2012, 36, 1141.
(9) For examples of allylic C−H bond oxidative activation with DDQ,
see: (a) Kiefer, E. F.; Lutz, F. E. J. Org. Chem. 1972, 37, 1519. (b) Iliefski,
T.; Li, S.; Lundquist, K. Tetrahedron Lett. 1998, 39, 2413. (c) Qin, C.;
Jiao, N. J. Am. Chem. Soc. 2010, 132, 15893. (d) Wang, T.; Xiang, S.-K.;
Qin, C.; Ma, J.-A.; Zhang, L.-H.; Jiao, N. Tetrahedron Lett. 2010, 52,
3208. (e) Liu, H.; Cao, L.; Sun, J.; Fossey, J. S.; Deng, W.-P. Chem.
Commun. 2012, 48, 2674. For an example of metal-free allylic
Full experimental details and characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: sowony73@hanyang.ac.kr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by both Basic Science Research
Program and Nano·Material Technology Department Program
through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education and MSIP (Nos.
2012R1A1A2041471, 2012M3A7B4049654, and 2014-011165).
amination, see: (f) Souto, J. A.; Zian, D.; Muniz, K. J. Am. Chem. Soc.
̃
2012, 134, 7242.
(10) (a) Newcomb, M. Tetrahedron 1993, 49, 1151. (b) Hollis, R.;
Hughes, L.; Bowry, V. W.; Ingold, K. U. J. Org. Chem. 1992, 57, 4284.
(c) Masnovi, J.; Samsel, E. G.; Bullock, R. M. J. Chem. Soc., Chem.
Commun. 1989, 1044.
(11) Liwosz, T. W.; Chemler, S. R. J. Am. Chem. Soc. 2012, 134, 2020.
(12) Owing to the structural feature of 2-alkenylanilines having
delocalized electron densities distributed along the extended conjugated
system, an alternative mechanistic pathway involving an electrophilic
addition of nitrogen radical cation to an alkene (via A′) cannot be
completely excluded.
REFERENCES
■
(1) (a) The Chemistry of Heterocyclic Compounds; Taylor, E. C., Saxton,
J. E., Eds.; Wiley-Interscience: New York, 1983 and 1994; Vol. 25.
(b) Sundberg, R. J. Indoles; Academic Press: New York, 1996.
(c) Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010,
110, 4489.
(2) (a) Inman, M.; Moody, C. J. Chem. Sci. 2013, 4, 29. (b) Shiri, M.
Chem. Rev. 2012, 112, 3508. (c) Platon, M.; Amardeil, R.; Djakovitch, L.;
D
dx.doi.org/10.1021/ol5015398 | Org. Lett. XXXX, XXX, XXX−XXX