Annulation of β-Enaminonitriles with Alkynes via RhIII-Catalyzed C-H Activation: Direct Access to Highly Substituted 1-Naphthylamines and Naphtho[1,8- bc]pyridines

Article abstract of DOI:10.1021/acs.orglett.8b02341

A Cp?Rh^III-catalyzed oxidative annulation of β-enaminonitriles with alkynes was reported to achieve selective synthesis of polysubstituted 1-naphthylamines and naphtho[1,8-bc]pyridines via multiple C-H activations. Assisted by a naphthylamine NH₂ group, 1-naphthylamines were also readily cyclized to produce naphtho[1,8-bc]pyridines. In addition, the obtained naphtho[1,8-bc]pyridine derivatives exhibit intense fluorescence in the solid state.

Full text of DOI:10.1021/acs.orglett.8b02341

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Annulation of β‑Enaminonitriles with Alkynes via RhIII-Catalyzed C−
H Activation: Direct Access to Highly Substituted 1‑Naphthylamines
and Naphtho[1,8-bc]pyridines
Haili Wang,† Hong Xu,† Bin Li,*,† and Baiquan Wang†,‡,§
†State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300071, China
§State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
S
* Supporting Information
ABSTRACT: A Cp*RhIII-catalyzed oxidative annulation of β-enami-
nonitriles with alkynes was reported to achieve selective synthesis of
polysubstituted 1-naphthylamines and naphtho[1,8-bc]pyridines via
multiple C−H activations. Assisted by a naphthylamine NH2 group, 1-
naphthylamines were also readily cyclized to produce naphtho[1,8-
bc]pyridines. In addition, the obtained naphtho[1,8-bc]pyridine
derivatives exhibit intense fluorescence in the solid state.
rhodium catalysis to selectively produce polysubstitued 1-
naphthylamines and naphtho[1,8-bc]pyridines via multiple C−
H activations (Scheme 1). The obtained 1-naphthylamines are
ver the past decade, transition-metal-catalyzed direct
Ofunctionalization of inert C−H bonds has emerged to be
an increasingly powerful tool for synthetic innovation.1 In
particular, Cp*RhIII complexes have been established as highly
active and versatile precatalysts in this field,2 which has allowed
the construction of various cyclic scaffolds in a more step-
economical and waste-reducing manner. In this context, diverse
approaches for heterocycle synthesis through RhIII-catalyzed C−
H activation and annulation strategies have been well-
documented.2,3 However, the formation of carbocyclic com-
pounds4 still lags behind. In particular, for six-membered
carbocycles, whereas substituted fused arenes5 and 1-naphthols6
have been accessed by catalytic C−H functionalization, the
preparation of 1-naphthylamine derivatives, to the best of our
knowledge, remains unexplored. In continuation of our interest
in transition-metal-catalyzed oxidative annulation reactions,6a,7
we envisioned that the application of a cyclization methodology
to construct substituted 1-naphthylamines would be highly
interesting and attractive if simple and readily available enamide
derivatives could be employed as reacting substrates.8 Enamides
have been frequently explored as valuable precursors in
transition-metal-catalyzed C−H bond activation, but the typical
end products are pyrroles and pyridines.9 Thus, the introduction
of a proper group to enamides might be a key point in
manipulating the reaction pathway.
Scheme 1. Rh(III)-Catalyzed Synthesis of Polysubstituted 1-
Naphthylamines and Naphtho[1,8-bc]pyridines
also readily converted into naphtho[1,8-bc]pyridines via a
naphthylamine NH2 group directed C−H/N−H bond
activation.10 Note that the nitrile group is essential for
carbocyclic 1-naphthylamine formations, as evidenced by the
recent report that oxidative coupling of β-enamino esters with
alkynes generated a six-membered N-containing heterocycle
intermediate in the first cyclization process.11 Importantly, the
resulting naphthylamine and naphtho[1,8-bc]pyridine scaffolds
are embedded in a large number of conjugated π-systems that
exhibit important electrochemical and photochemical properties
with potential applications as organic semiconductors and
luminescence materials.12
Our initial attempt to synthesize a substituted 1-naphthyl-
amine involved reaction of 3-amino-3-phenylacrylonitrile (1a)
and diphenylacetylene (2a) as model substrates in the presence
of [Cp*RhCl2]2 catalysts. To our delight, the reaction did
proceed to give the desired cyclized product 3a in 26% isolated
According to our previous observation on the significance of
the nitrile group in the oxidative coupling of benzoylacetonitriles
with alkynes, as well as the corresponding cyclization of ortho-
substituted benzoylacetonitriles to 1-naphthol derivatives,6a β-
enaminonitriles were chosen to verify our hypothesis. Indeed, 3-
amino-3-arylacrylonitriles were suitable synthons for this
transformation. We herein disclose our new development of
oxidative annulation of β-enaminonitriles with alkynes under
Received: July 25, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02341
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
yield at 80 °C in DMF (Table 1, entry 1). The structure of 3a
Scheme 2. Substrate Scope of Oxidative Annulation of 3-
Amino-3-arylacrylonitriles to 1-Naphthylamines
a
was established by 1H and 13C NMR analysis as well as HRMS
a
Table 1. Optimization of the Reaction Conditions
b
entry
1
2
additive (equiv)
solvent
temp (°C) yield (%)
DMF
DMF
MeCN
DCE
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
dioxane
80
80
80
80
80
26
c
NR
trace
trace
52
3
4
5
d
6
80
44
e
7
f
80
23
8
80
60
NR
trace
57
62
58
66
77
80
9
10
11
12
13
14
15
100
100
100
100
100
100
PivOH (2.0)
AgOAc (0.2)
AgOAc (0.2) + PivOH (2.0)
AgOAc (0.2) + PivOH (4.0)
AgOAc (0.2) + PivOH (4.0)
a
Reaction conditions: 1a (0.2 mmol, 1.0 equiv), 2a (0.2 mmol),
[Cp*RhCl2]2 (5 mol %), Cu(OAc)2·H2O (2.0 equiv), additive
b
c
(equiv), solvent (2.0 mL), Ar, temp, 18 h. Isolated yield. No [Rh]
a
b
d
e
Reactions in 0.2 mmol scale (0.1 M), isolated yield. 4.0 mmol scale
catalyst. Cu(OAc)2 was used instead of Cu(OAc)2·H2O. AgOAc
was used instead of Cu(OAc)2·H2O. Ag2CO3 was used instead of
c
f
reaction. The structure of major regioisomer is shown.
Cu(OAc)2·H2O. NR = no reaction.
This effect is more pronounced for the meta-fluoro substituent,
thereby leading to the site selectivity that afforded the more
sterically hindered compound 3l as the major products.
Interestingly, no steric influence at the ortho position was
found as 3o (90%) and 3p (99%) were isolated in even higher
yields.15 We found that several functional groups, such as
methoxy (3c, 3k, and 3o), trifluoromethyl (3e), fluoro (3f, 3l,
and 3p), chloro (3g and 3m), bromo (3h and 3n), and nitrile
(3i), remained intact under the present reaction conditions.
Moreover, as shown for 3a (58%) and 3h (69%), scale-up
reactions (4 mmol) provided moderate yield, thereby
demonstrating the practicality of this method. Unfortunately,
1-naphthyl, 2-naphthyl, 2-thienyl, 2-pyridyl, 3-pyridyl, and 4-
pyridyl derived β-enaminonitriles exhibited very low or no
reactivity under the current reaction conditions.
Next, we expanded the scope of this protocol to other alkyne
substrates. As shown in Scheme 2, the present catalytic system
could be extended effectively to a variety of symmetric
diarylacetylenes containing methyl, methoxy, fluoro, chloro,
bromo, and acetyl groups (3q−3v). Unsymmetrical aryl alkyl-
disubstituted alkyne was also a suitable coupling partner, albeit
with low regioselectivity. For example, prop-1-ynylbenzene gave
rise to regioisomers 3w and 3w′ in a 1.1:1 ratio. In contrast,
dialkyl-substituted alkynes and terminal alkynes failed to work
under the standard conditions, which is indicative of the
limitation of the method.
spectrometry. As expected, no conversion was observed in the
absence of rhodium catalyst (entry 2). Solvent screening
revealed that THF was superior to DMF, MeCN, and DCE,
leading to a higher yield (entries 1, 3−5). Among different
oxidants evaluated, Cu(OAc)2·H2O was found to be optimal.
Other oxidants including Cu(OAc)2, AgOAc, and Ag2CO3
proved to be less effective or even ineffective (entries 6−8).
The reaction efficiency was also sensitive to the reaction
temperatures. Thus, the reaction was inactive when performed
at 60 °C (entry 9), whereas higher reaction temperature (100
°C) gave a better result (entry 10). Various additives were then
investigated on the benchmark reaction.13 It was surprising to
observe that although AgOAc (0.2 equiv) and PivOH (2.0
equiv) individually hardly promoted the reaction efficiency
(entries 11 and 12), a combination of these two additives
brought about notable progress in product yield (entry 13).
Addition of 4.0 equiv of PivOH further enhanced the catalytic
activity, and the yield of 3a was increased to 80% in dioxane
(entries 14 and 15).
With the promising optimal conditions, the reaction scope
with respect to β-enaminonitrile was first explored (Scheme 2).
A host of 3-amino-3-arylacrylonitriles could all be cyclized with
good to excellent yields. Although various para-substituted
substrates were coupled without difficulty (3a−3i), the desired
cyclization was found to proceed more efficiently with halide
groups (3f−3h). For substrates with meta-methyl, meta-chloro,
or meta-bromo substituents, the most accessible aromatic C−H
bond was preferentially activated (3j, 3m, and 3n). However,
two regioisomers 3k and 3k′ were obtained in a 2:1 ratio from a
meta-methoxy-substituted substrate, indicating a considerable
secondary directing group effect on the C−H bond activation.14
To gain insight into the mechanism of this catalytic process,
we next conducted preliminary mechanistic studies.13 First,
intermolecular competition experiments between 1c and 1h
with 2a showed electron-deficient substrates to be preferentially
functionalized (Scheme S1-a), which suggests that the C−H
activation step might not proceed in a simple electrophilic
B
DOI: 10.1021/acs.orglett.8b02341
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
aromatic substitution process. Second, the H/D exchange
experiment of 1a revealed that the ortho C−H bond cyclo-
metalated step is irreversible (Scheme S1-b). Finally, parallel
intermolecular kinetic isotope effect experiments were studied
between 1a and 1a-d5, and a value of kH/kD ≈ 2.3 was observed
(Scheme S1-c), demonstrating that cleavage of the C−H bond is
likely involved in the turnover-limiting step.16
Table 2. Substrate Scope of Oxidative Annulation of 1-
Naphthylamines with Alkynes
a
On the basis of the above experimental results and the
literature precedents,6,7 a tentative reaction mechanism was
proposed for this naphthylamine synthesis (Scheme 3). The
entry
3, R1
2, R2
4
yield (%)
1
2
3
4
5
6
7
3a, R1 = H
3g, R1 = Cl
3h, R1 = Br
3a, R1 = H
3a, R1 = H
3a, R1 = H
3a, R1 = H
2a, R2 = Ph
4a
4b
4c
4d
4e
4f
93
63
68
87
80
31
55
2a, R2 = Ph
2a, R2 = Ph
Scheme 3. Proposed Mechanism for Oxidative Annulation of
3-Amino-3-arylacrylonitriles to 1-Naphthylamines
2b, R2 = 4-MeC6H4
2d, R2 = 4-FC6H4
2i, R2 = Et
2j, R2 = n-Pr
4g
a
Reactions in 0.2 mmol scale (0.1 M), isolated yield.
Scheme 4. Substrate Scope of Oxidative Annulation of 3-
a
Amino-3-arylacrylonitriles to Naphtho[1,8-bc]pyridines
enamine resonance structure 1a′ imparts the C(2) atom certain
nucleophilic characteristics.17 As a result, a five-membered
rhodacylic intermediate A is formed initially through the
reaction of β-enaminonitrile with the [Cp*RhIII] species
generated from [Cp*RhCl2]2 and AgOAc, which involves an
irreversible C-coordination and carboxylate-assisted cleavage of
the ortho C(sp2)−H bond.18 Subsequently, coordination and
migratory insertion of alkyne 2a furnishes a seven-membered
rhodacycle B. Tautomerization of B leads to the formation of
intermedate C,19 which then undergoes reductive elimination to
afford the final product 3a along with a RhI species. The RhI
species is oxidized into the catalytically active RhIII complex with
the aid of copper oxidant.
With the satisfactory results obtained for the synthesis of
polysubstituted 1-naphthylamine products, we anticipated that a
further annulation with alkyne might take place under the
assistance of the naphthylamine NH2 group to yield tricyclic
heteroaromatic compounds. Indeed, a screening of reaction
conditions under rhodium(III) catalysis in THF, by using 3a
and 2a as the coupling partners, confirmed a reaction with
participation of Cu(OAc)2 as an oxidant and K3PO4 as an
additive. The corresponding naphtho[1,8-bc]pyridine 4a was
thus obtained in 93% isolated yield (Table 2, entry 1).
Furthermore, substituted naphthylamines (3g and 3h) and
diarylacetylenes (2b and 2d) reacted smoothly to provide the
desired tricyclic products 4b−4e (entries 2−5). This method-
ology could also be extended to dialkyl-substituted alkynes, as
well, albeit in somewhat lower efficiency (entries 6 and 7).
In light of the results shown in Scheme 2 and Table 2, we
speculated that the construction of naphtho[1,8-bc]pyridines 4
could be achieved in a tandem process by employing
enaminonitrile 1 as starting substrates. As shown in Scheme 4,
this was indeed the case; the cyclizations were readily carried out
following a slightly modified Rh(III)-catalyzed conditions
depicted in Table 2. To our satisfaction, all reactions gave the
corresponding naphtho[1,8-bc]pyridine products (4a−c, 4h−
a
Reactions in 0.15 mmol scale (0.075 M), isolated yield.
4s, Scheme 4) in moderate to high yields under the optimized
reaction conditions.20 Particularly noteworthy was that the
naphtho[1,8-bc]pyridine derivatives 4 obtained above showed
solid-state fluorescence in a range of 470−600 nm. In particular,
compound 4a was found to exhibit more intense luminescence
(λemis = 534 nm).13
In summary, we have developed a general and selective
construction of polysubstitued 1-naphthylamines and naphtho-
[1,8-bc]pyridines via rhodium(III)-catalyzed multiple C−H
activation and cyclization reactions of β-enaminonitriles with
internal alkynes. To the best of our knowledge, this is the first
example of 1-naphthylamine synthesis via a catalytic C−H
functionalization approach. Meanwhile, the obtained 1-naph-
thylamines can be transformed to naphtho[1,8-bc]pyridine
derivatives through C−H/N−H bond activations by the
direction of the naphthylamine NH2 group. All of these catalytic
approaches exhibit good functional group tolerance and broad
substrate scope. Given the rapid assembly of otherwise hard to
access skeletons, we anticipate that these protocols will facilitate
the synthesis of related complex structures.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.8b02341.
C
DOI: 10.1021/acs.orglett.8b02341
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Full experimental procedures, additional experimental
Letter
Angew. Chem., Int. Ed. 2014, 53, 1529. (g) Seoane, A.; Casanova, N.;
̃ ̃
Quinones, N.; Mascarenas, J. L.; Gulías, M. J. Am. Chem. Soc. 2014, 136,
data, analytical data, and characterization of new
7607. (h) Zhou, M. B.; Pi, R.; Hu, M.; Yang, Y.; Song, R. J.; Xia, Y.; Li, J.
H. Angew. Chem., Int. Ed. 2014, 53, 11338. (i) Yu, S.; Liu, S.; Lan, Y.;
Wan, B.; Li, X. J. Am. Chem. Soc. 2015, 137, 1623. (j) Zheng, J.; Wang, S.
B.; Zheng, C.; You, S. L. J. Am. Chem. Soc. 2015, 137, 4880. (k) Lv, N.;
Chen, Z.; Liu, Y.; Liu, Z.; Zhang, Y. Org. Lett. 2017, 19, 2588.
(5) (a) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem.,
Int. Ed. 2008, 47, 4019. (b) Wu, Y.-T.; Huang, K.-H.; Shin, C.-C.; Wu,
T.-C. Chem. - Eur. J. 2008, 14, 6697. (c) Shi, Z.; Tang, C.; Jiao, N. Adv.
Synth. Catal. 2012, 354, 2695. (d) Pham, M. V.; Cramer, N. Angew.
Chem., Int. Ed. 2014, 53, 3484. (e) Zhang, X.; Yu, X.; Ji, D.; Yamamoto,
Y.; Almansour, A. I.; Arumugam, N.; Kumar, R. S.; Bao, M. Org. Lett.
2016, 18, 4246.
compounds (1H, 13C, and 19F NMR spectra) (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: nklibin@nankai.edu.cn.
ORCID
Bin Li: 0000-0003-3909-3796
Baiquan Wang: 0000-0003-4605-1607
Notes
(6) (a) Tan, X.; Liu, B.; Li, X.; Li, B.; Xu, S.; Song, H.; Wang, B. J. Am.
Chem. Soc. 2012, 134, 16163. (b) Peng, S.; Wang, L.; Wang, J. Chem. -
Eur. J. 2013, 19, 13322. (c) Naresh, G.; Kant, R.; Narender, T. Org. Lett.
2015, 17, 3446. (d) Zhou, S.; Wang, J.; Wang, L.; Song, C.; Chen, K.;
Zhu, J. Angew. Chem., Int. Ed. 2016, 55, 9384. (e) Xie, F.; Yu, S.; Qi, Z.;
Li, X. Angew. Chem., Int. Ed. 2016, 55, 15351. (f) Li, Y.; Wang, Q.; Yang,
X.; Xie, F.; Li, X. Org. Lett. 2017, 19, 3410. (g) Zhou, C.; Fang, F.;
Cheng, Y.; Li, Y.; Liu, H.; Zhou, Y. Adv. Synth. Catal. 2018, 360, 2546.
(7) (a) Zhou, T.; Li, B.; Wang, B. Chem. Commun. 2016, 52, 14117.
(b) Zhou, T.; Wang, Y.; Li, B.; Wang, B. Org. Lett. 2016, 18, 5066.
(c) Li, B.; Xu, H.; Wang, H.; Wang, B. ACS Catal. 2016, 6, 3856.
(d) Wang, H.; Wang, B.; Li, B. J. Org. Chem. 2017, 82, 9560. (e) Zhou,
T.; Li, B.; Wang, B. Chem. Commun. 2017, 53, 6343.
(8) For an example of 1-naphthylamine synthesis via hypervalent
iodine(III)-mediated annulation of 3-amino-3- phenylacrylonitrile with
phenylacetylene, see: Gao, P.; Liu, J.; Wei, Y. Org. Lett. 2013, 15, 2872.
(9) (a) Rakshit, S.; Patureau, F.-W.; Glorius, F. J. Am. Chem. Soc. 2010,
132, 9585. (b) Huestis, M. P.; Chan, L.; Stuart, D. R.; Fagnou, K. Angew.
Chem., Int. Ed. 2011, 50, 1338. (c) Zhao, M.-N.; Ren, Z.-H.; Wang, Y.-
Y.; Guan, Z.-H. Chem. Commun. 2012, 48, 8105. (d) Li, B.; Wang, N.;
Liang, Y.; Xu, S.; Wang, B. Org. Lett. 2013, 15, 136. (e) Wang, L.;
Ackermann, L. Org. Lett. 2013, 15, 176. (f) Zhao, M.-N.; Ren, Z.-H.;
Wang, Y.-Y.; Guan, Z.-H. Org. Lett. 2014, 16, 608.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(21372121 and 21672108) for their generous financial support.
■
REFERENCES
■
(1) For selected recent reviews on C−H functionalization, see:
(a) Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev.
̈
2011, 40, 4740. (b) Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111,
1215. (c) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev.
2011, 40, 5068. (d) Li, B.-J.; Shi, Z.-J. Chem. Soc. Rev. 2012, 41, 5588.
(e) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H. Chem. Rev. 2012, 112,
5879. (f) Huang, H.; Ji, X.; Wu, W.; Jiang, H. Chem. Soc. Rev. 2015, 44,
1155. (g) Moselage, M.; Li, J.; Ackermann, L. ACS Catal. 2016, 6, 498.
(h) Yoshino, T.; Matsunaga, S. Adv. Synth. Catal. 2017, 359, 1245.
(i) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q. Chem. Rev. 2017,
117, 8754. (j) Yang, Y.; Lan, J.; You, J. Chem. Rev. 2017, 117, 8787.
(k) Wei, Y.; Hu, P.; Zhang, M.; Su, W. Chem. Rev. 2017, 117, 8864.
(l) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247.
(2) For selected reviews on Rh(III)-catalyzed C−H activation, see:
(a) Satoh, T.; Miura, M. Chem. - Eur. J. 2010, 16, 11212. (b) Patureau,
F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica Acta 2012, 45, 31.
(c) Chiba, S. Chem. Lett. 2012, 41, 1554. (d) Song, G.; Wang, F.; Li, X.
(10) For selected examples on free amine directed C−H
functionalization, see: (a) Morimoto, K.; Hirano, K.; Satoh, T.;
Miura, M. Chem. Lett. 2011, 40, 600. (b) Suzuki, C.; Morimoto, K.;
Hirano, K.; Satoh, T.; Miura, M. Adv. Synth. Catal. 2014, 356, 1521.
(c) Yi, Y.; Lee, H.; Jun, C. H. Chem. Commun. 2016, 52, 10171.
(d) Chu, H.; Xue, P.; Yu, J. T.; Cheng, J. J. Org. Chem. 2016, 81, 8009.
(e) Bai, P.; Huang, X. F.; Xu, G. D.; Huang, Z. Z. Org. Lett. 2016, 18,
3058.
̈
Chem. Soc. Rev. 2012, 41, 3651. (e) Kuhl, N.; Schroder, N.; Glorius, F.
Adv. Synth. Catal. 2014, 356, 1443. (f) Song, G.; Li, X. Acc. Chem. Res.
2015, 48, 1007. (g) Ye, B.; Cramer, N. Acc. Chem. Res. 2015, 48, 1308.
̃
(h) Gulías, M.; Mascarenas, J. L. Angew. Chem., Int. Ed. 2016, 55, 11000.
(i) Piou, T.; Rovis, T. Acc. Chem. Res. 2018, 51, 170. (j) Vasquez-
́
́
Cespedes, S.; Wang, X.; Glorius, F. ACS Catal. 2018, 8, 242.
(11) Peng, S.; Liu, S.; Zhang, S.; Cao, S.; Sun, J. Org. Lett. 2015, 17,
(3) (a) Wu, X.-F., Ed. Transition-Metal-Catalyzed Heterocycle Synthesis
via C−H Activation; Wiley: Weinheim, 2016. (b) Stuart, D. R.; Alsabeh,
P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 18326. (c) Shi,
Z.; Koester, D. C.; Boultadakis-Arapinis, M.; Glorius, F. J. Am. Chem.
Soc. 2013, 135, 12204. (d) Wang, C.; Sun, H.; Fang, Y.; Huang, Y.
Angew. Chem., Int. Ed. 2013, 52, 5795. (e) Liu, B.; Song, C.; Sun, C.;
Zhou, S.; Zhu, J. J. Am. Chem. Soc. 2013, 135, 16625. (f) Fukui, Y.; Liu,
P.; Liu, Q.; He, Z.-T.; Wu, N.-Y.; Tian, P.; Lin, G.-Q. J. Am. Chem. Soc.
2014, 136, 15607. (g) Zheng, L.; Hua, R. Chem. - Eur. J. 2014, 20, 2352.
(h) Zhang, G.; Yu, H.; Qin, G.; Huang, H. Chem. Commun. 2014, 50,
4331. (i) Zhao, S.; Yu, R.; Chen, W.; Liu, M.; Wu, H. Org. Lett. 2015,
17, 2828. (j) Hong, S. Y.; Jeong, J.; Chang, S. Angew. Chem., Int. Ed.
2017, 56, 2408. (k) Wu, J.-Q.; Zhang, S.-S.; Gao, H.; Qi, Z.; Zhou, C.-J.;
Ji, W.-W.; Liu, Y.; Chen, Y.; Li, Q.; Li, X.; Wang, H. J. Am. Chem. Soc.
2017, 139, 3537. (l) Yang, X.; Liu, S.; Yu, S.; Kong, L.; Lan, Y.; Li, X.
Org. Lett. 2018, 20, 2698.
(4) (a) Boyarskiy, V. P.; Ryabukhin, D. S.; Bokach, N. A.; Vasilyev, A.
V. Chem. Rev. 2016, 116, 5894. For selected examples of Rh(III)-
catalyzed five-membered carbocycle synthesis, see: (b) Patureau, F. W.;
Besset, T.; Kuhl, N.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2154.
(c) Muralirajan, K.; Parthasarathy, K.; Cheng, C.-H. Angew. Chem., Int.
Ed. 2011, 50, 4169. (d) Li, B.-J.; Wang, H.-Y.; Zhu, Q.-L.; Shi, Z.-J.
Angew. Chem., Int. Ed. 2012, 51, 3948. (e) Shi, X.; Li, C.-J. Org. Lett.
5032.
(12) (a) Miao, Q., Ed. Polycyclic Arenes and Heteroarenes: Synthesis,
Properties, and Applications; Wiley-VCH: New York, 2015. (b) Wang,
C.; Dong, H.; Hu, W.; Liu, Y.; Zhu, D. Chem. Rev. 2012, 112, 2208.
(c) Facchetti, A. Chem. Mater. 2011, 23, 733.
(13) See the Surporting Information for details.
(14) Balcells, D.; Clot, E.; Eisenstein, O. Chem. Rev. 2010, 110, 749.
(15) Although the exact reason is unclear, we presumed that the
interactions between the adjacent “F” and “H2N” (could be hydrogen
bond or others) make the whole molecule more coplanar, which is
beneficial to the C−H bond metalation step, thus leading to excellent
product yields of 3p.
(16) Simmons, E. M.; Hartwig, J. F. Angew. Chem., Int. Ed. 2012, 51,
3066.
(17) (a) Erian, A. W. Chem. Rev. 1993, 93, 1991. (b) Conn, J. J.;
Taurins, A. Can. J. Chem. 1953, 31, 1211.
(18) Ackermann, L. Chem. Rev. 2011, 111, 1315.
(19) Fu, X.; Shang, Z.; Xu, X. J. Org. Chem. 2016, 81, 8378.
(20) Dialkyl-substituted alkynes were not suitable for the tandem
transformation to furnish naphtho[1,8-bc]pyridine products because
they were unreactive in the first cyclization step for 1-naphthylamine
synthesis.
́
2013, 15, 1476. (f) Mehta, V. P.; García-Lopez, J.-A.; Greaney, M. F.
D
DOI: 10.1021/acs.orglett.8b02341
Org. Lett. XXXX, XXX, XXX−XXX