Silver-catalyzed three-component approach to quinolines starting from anilines, aldehydes, and alcohols

Article abstract of DOI:10.1055/s-0035-1561916

A silver-catalyzed sequential formation of two C-C bonds for the construction of a series of polysubstituted quinolines from anilines, aldehydes, and alcohols under mild conditions has been developed. The transformation is effective for a broad range of substrates, including aliphatic alcohols, arylalkanols, cycloalkanols, and ethylene glycol, thereby permitting the expansion of the constituent architectures of the heterocyclic framework.

Full text of DOI:10.1055/s-0035-1561916

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–F
letter
A
X. Zhang et al.
Letter
Synlett
Silver-Catalyzed Three-Component Approach to Quinolines Start-
ing from Anilines, Aldehydes, and Alcohols
Xu Zhang*
OH
N
R2
R3
Wenmin Liu
Ruixue Sun
Xuefeng Xu
Zhiqiang Wang*
Yanlei Yan
R1
AgOTf (5 mol%)
HOTf (10 mol%)
NH2
+
R3
R2 CHO
R4
HO
R5
toluene, air
120 °C, 12 h
R1
N
R2
R4
School of Chemistry and Pharmacony Engineering,
Nanyang Normal University, Nanyang 473061,
P. R. of China
R1
R3 = alkyl, aryl, COOEt
28 examples
R4 = Ph; R5 = Ph, H, Me
8 examples
R5
zhangxuedu@126.com
yield: 34–96%
yield: 64–86%
Received: 19.12.2015
Accepted after revision: 08.02.2016
Published online: 14.03.2016
new methods for the synthesis of substituted quinolines is
an area of considerable ongoing interest.11
Recently, Jiang and co-workers established a novel pro-
tocol, based on the palladium-catalyzed sequential forma-
tion of two C–C bonds, for the construction of a series of 2-
substituted and 2,3-disubstituted quinolines from aryl
amines, aldehydes, and terminal olefins.12 In their develop-
ment of a silver-mediated tandem protocol for the synthe-
sis of quinolines through oxidative coupling/cyclization of
N-aryl imines and alkynes, Zhu and co-workers demon-
strated that metalation occurs at the ortho C–H bond of the
N-aryl imine through protonation-driven enhancement of
its acidity by virtue of the carbophilic π-acidity of silver.13
An efficient and regioselective synthesis of polysubstituted
quinolines from diaryliodonium compounds, alkynes, and
nitriles, has been presented by Li and co-workers.14 Al-
though many methods have been developed for the modifi-
cation of quinolines,15 the various routes suffer from a
range of problems, such as harsh conditions, high numbers
of steps, the need for large amounts of promoters such as
bases, the use of expensive and/or harmful metals, or limit-
ed tolerance of functional groups. Consequently, the use of
inexpensive starting materials and environmentally benign
oxidants in an atom-efficient method would be particularly
attractive.
DOI: 10.1055/s-0035-1561916; Art ID: st-2015-w0986-l
Abstract A silver-catalyzed sequential formation of two C–C bonds for
the construction of a series of polysubstituted quinolines from anilines,
aldehydes, and alcohols under mild conditions has been developed. The
transformation is effective for a broad range of substrates, including al-
iphatic alcohols, arylalkanols, cycloalkanols, and ethylene glycol, there-
by permitting the expansion of the constituent architectures of the het-
erocyclic framework.
Key words silver, catalysis, amines, aldehydes, alcohols, quinolines
The presence of polysubstituted quinolines as key struc-
tural units in many natural products and pharmaceuticals1
has spurred the development of various methods for the
synthesis of these heterocycles.2 Furthermore, polysubsti-
tuted quinolines are useful ligands for the preparation of
materials for use in organic light-emitting diodes or as
asymmetric catalysts.3 Substituents on the quinoline rings
have a marked influence on the properties of these com-
pounds;4 consequently, efficient methods for the prepara-
tion of a diverse range of polysubstituted quinolines are
highly desirable.
Classical strategies for the preparation of substituted
quinolines include the Skraup,5 Doebner–von Miller,6 Doeb-
ner,7 Combes,8 Pfitzinger,9 and Friedländer protocols.10
However, most of these synthetic approaches require high
temperatures or harsh conditions, so the development of
Here, we present a highly efficient method for synthe-
sizing polysubstituted quinolines from three readily avail-
able components: an aniline, an aldehyde, and an alcohol,
as exemplified in Scheme 1. To the best of our knowledge,
CHO
N
Ph
NH2
OH
catalyst (5 mol%)
+
+
solvent, temp
24 h
Ph
Scheme 1 Synthesis of a polysubstituted quinoline
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

B
X. Zhang et al.
Letter
Synlett
this is the first report of the use of alcohols in a silver-medi-
ated synthesis of quinolines.
additive, and toluene as the solvent to permit the tandem
oxidative coupling/cyclization reaction to be carried out
under air.
At the outset of this investigation, we explored the Ag-
catalyzed reaction of benzaldehyde with aniline and 2-
phenylethanol to give 2,4-diphenylquinoline. We found
that AgOTf was an indispensable species in driving the cata-
lytic process, and that protonation enhanced the C–H acidi-
ty,16 so that the addition of HOTf greatly improved the yield
of the product.17 Furthermore, the reaction proceeded effi-
ciently in air to give an excellent yield of the product. After
extensive screening of the reaction conditions (silver cata-
lyst, additive, and solvent), we concluded that the optimal
conditions involved the use of AgOTf as catalyst, HOTf as
Having established the optimal conditions, we exam-
ined the scope and limitations of our reaction for the syn-
thesis of substituted quinolines (Scheme 2). Initially, a se-
ries of aldehydes 2 were treated with anilines 1, and 2-aryl-
ethanols 3 to give a variety of substituted quinolines 4.17
The reactions of formaldehyde, acetaldehyde, benzalde-
hyde, furan-2-carbaldehyde, and ferrocene-2-carbaldehyde
all proceeded smoothly under the standard conditions to
give the expected quinolines 4 in moderate to excellent iso-
lated yields, regardless of the electron-donating or electron-
N
R2
R1
NH2
OH
AgOTf, HOTf
R1
R2 CHO
R3
+
+
toluene, air
120 °C, 12 h
4
1
R3
2
3
N
R1
N
N
N
R1
R1
R1
4a: R1 = Me, 78%
4b: R1 = OMe, 76%
4c: R1 = F, 64%
4d: R1 = F, 70%
4e: R1 = Me, 89%
4f: R1 = OMe, 89%
4g: R1 = F, 76%
4h: R1 =CF3, 72%
4i: R1 = Me, 90%
4j: R1 = OMe, 94%
4k: R1 = F, 80%
R1
N
N
N
N
O
Fe
F
F
4l: R1 = Me, 84%
4m: R1 = OMe, 82%
4n: R1 = F, 70%
4p: 83%
4q: 72%
4o: 84%
O
O
N
N
N
R1
R1
4r: 93%
4s: R1 = Me, 96%
4t: R1 = OMe, 96%
4u: R1 = Me, 94%
4v: R1 = OMe, 95%
Scheme 2 Scope for the synthesis of polysubstituted quinolines 4. Reaction conditions: arylamine 1 (0.5 mmol), aldehyde 2 (0.5 mmol), 2-arylethanol
3 (0.75 mmol), AgOTf (0.025 mmol, 5 mol%), HOTf (0.05 mmol, 10 mol%), toluene (2 mL), 120 °C, under air, 12 h. Yields of isolated products are
reported.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

C
X. Zhang et al.
Letter
Synlett
withdrawing nature of the substituents on the aniline ring.
The reactions with formaldehyde gave 4-substituted quino-
lines 4a–d in yields of 64–78% (Scheme 2). The reactions of
para-substituted anilines gave the corresponding 6-substi-
tuted quinolines in excellent yields. Interestingly, meta-sub-
stituted anilines did not give mixtures of 5- and 7-substi-
tuted substituted quinolines, but instead gave 7-substituted
quinolines exclusively in high yields. The efficient forma-
tion of products from anilines carrying an electron-with-
drawing substituent suggests a mechanism involving acidic
C–H bond activation, as opposed to one involving ring clo-
sure through an electrophilic aromatic substitution.
Next, we evaluated a variety of alcohols 3′ in eactions
with anilines 1 and aldehydes 2 to give quinolines 5 with
various substituents. The reactions of the aliphatic alcohols
propan-1-ol, butan-1-ol, pentan-1-ol, and hexan-1-ol all
proceeded smoothly under the standard conditions, and
gave the expected quinolines 5b–f, respectively, in moder-
ate to excellent yields upon isolation (Scheme 3), although
ethanol gave 5a in a relatively low yield. Further investiga-
tions toward improving yields of products from ethanol as a
substrate are ongoing in our laboratory. Both electron-defi-
cient and electron-rich alcohol components delivered the
corresponding products in good to excellent yields. Mor-
R2
R3
NH2
R3
HO
R4
N
standard
conditions
R1
R1
+
R2 CHO
+
1
5
R4
2
3'
N
N
OH
COOn-Bu
HO
COOn-Bu
5a: 34%
R
5g: 67%
N
N
COOEt
OH
OH
COOEt
5b: R = H, 53%
5c: R = Me, 62%
5h: 84%
N
N
OH
(CH2)3
OH
(CH2)2
5d: 72%
5i: 54%
N
H
N
OH
N
OH
(CH2)4
F3C
O
NH
(CH2)3
O
5e: 88%
5j: 72%
N
N
OH
(CH2)5
OH
(CH2)4
5k: 86%
5f: 82%
Scheme 3 Scope of alcohols 3′ in the synthesis of polysubstituted quinolines. Reaction conditions: arylamine 1 (0.5 mmol), aldehyde 2 (0.5 mmol),
alcohol 3′ (0.75 mmol), AgOTf (0.025 mmol, 5 mol%), HOTf (0.05 mmol, 10 mol%), toluene (2 mL), 120 °C, under air, 12 h. Yields of isolated products
are reported.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

D
X. Zhang et al.
Letter
Synlett
pholin-3-ol and indan-2-ol also reacted smoothly to afford
quinolines 5j and 5k in excellent yields. Gratifyingly, all the
reactions showed the same regioselectivity.
results confirmed that insertion of the alkene into the C–Ag
bond is followed by abstraction of a hydrogen atom from
the N-benzylidene aniline.
To further demonstrate the scope of our reaction for the
preparation of polysubstituted quinolines, we next turned
our attention to cycloalkanols 3′′ as substrates (Scheme 4).
Under the standard reaction conditions, the reactions of
various cycloalkanols 3′′ with anilines 1 and aldehydes 2 to
give the corresponding polysubstituted quinolines 6 pro-
ceeded well. The structure of cyclobuta[c]quinoline 6a was
confirmed by X-ray crystal diffraction.18
D
N
D/H
+
standard
conditions
N
D
N
(1)
KH/KD = 1.05:1
Ph
+
OH
N
R1
standard
conditions
NH2
+
R1
OH
R2 CHO
+
(CH2)n
N
N
(CH2)n
1
2
3''
6
52%
+
Ph
N
N
standard
conditions
N
N
(2)
F3C
+
OH
6a: 64%
6b: 73%
F3C
O
22%
Ph
N
N
Ph
standard
conditions
N
Ph
N
(3)
(4)
Ph
Ph
N
6c: 87%
6d: 67%
0%
0%
Scheme 4 Scope of cycloalkanols 3′′in the synthesis of polysubstitut-
ed quinolines. Reaction conditions: arylamine 1 (0.5 mmol), aldehyde 2
(0.5 mmol), cycloalkanol 3′′ (0.75 mmol), AgOTf (0.025 mmol, 5
mol%), HOTf (0.05 mmol, 10 mol%), toluene (2 mL), 120 °C, under air,
12 h. Yields of isolated products are reported.
NH2
standard
CHO
Ph
conditions
+
To probe the mechanism of the C–H bond cleavage, a 1:1
mixture of (4-tolyl)[(4-tolyl)methylene]amine and its 2,6-
deuterated derivative was subjected to the standard reac-
tion conditions to determine the intermolecular isotope ef-
fect (Scheme 5, reaction 1). A slight kinetic isotope effect
(kH/kD = 1.05) was observed, showing that the rate-limiting
step does not involve C–H cleavage of the imine. In a com-
petition study carried out with an imine bearing an elec-
tron-withdrawing group and an imine bearing an electron-
donating group, the electron-withdrawing imine slightly
dominated the product formation (Scheme 5, reaction 2).
Furthermore, the efficiency of formation of products from
anilines with electron-withdrawing groups is suggestive of
an acidic C–H bond-activation mechanism. To examine
whether an alkene intermediate formed through dehydra-
tion of the alcohol reacts with the carbon of the C=N moiety
or inserts into the C–Ag bond, and whether elimination oc-
curs after the initial protodemetalation to give an alkenylat-
ed imine or during the cyclization process, we performed
five independent reactions (Scheme 5, reactions 3–7). The
standard
CHO
NH2
N
Ph
Ph
conditions
(5)
(6)
+
OH
54%
NH2
standard
CHO
N
conditions
+
92%
standard
CHO
NH2
conditions
no reaction
+
(7)
Scheme 5 Mechanistic studies
On the basis of the above results, we propose the cata-
lytic cycle shown in Scheme 6. In the reaction, silver acts
not only as a transition-metal catalyst, but also as a Lewis
acid. Consequently, dehydration of the alcohol to form an
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

E
X. Zhang et al.
Letter
Synlett
NH2
+
CHO
H
H+
N
N
Ag+
H+
H
N
A
Ag
OH
H+, Ag+
H
N
N
N
[O]
Ag
D
Ag
B
C
Scheme 6 Possible mechanism for the silver-catalyzed cyclization reaction of an aldehyde, amine, and alcohol
alkene intermediate should be possible under the reaction
conditions. Simultaneously, the reaction is initiated by the
silver-catalyst-activated N-benzylideneaniline, formed in
situ from the aniline and aldehyde precursors, to give inter-
mediate A. Subsequent insertion of the alkene into the C–Ag
bond is followed by abstraction of a hydrogen atom from
the N-benzylideneaniline to give intermediate B. Subse-
quent reductive elimination generates tetrahydroquinoline
C through a Povarov reaction, with release of silver. Inter-
mediate C then undergoes aerial oxidation to give the cor-
responding quinoline D. Under the high-temperature acidic
conditions, the silver is oxidized by O2 to restore the Ag(I)
catalyst.
sion of the constituent architectures of the heterocyclic
framework. The efficiency and functional-group tolerance
of this procedure were fully demonstrated by synthesizing
a number of substituted quinolines. Because of the relative-
ly low cost of the catalytic system and the commercial
availability of the starting materials, this method should
find widespread use, including in the industrial field. Fur-
standard
conditions
NH2
+
N
R1
HOH2C
R2 CHO
+
CH2OH
7
2
On the basis is this catalytic cycle, we surmised that the
ethylene glycol might react more readily than ethanol, be-
cause silver is a better catalyst for reactions of ethylene gly-
col. To our delight, aniline and a range of aldehydes 2 react-
ed smoothly with ethylene glycol to give the corresponding
2-substituted quinolines 7 in good to excellent yields; ferro-
cene-2-carbaldehyde, cyclohexanecarbaldehyde, 1-naph-
thaldehyde, thiophene-2-carbaldehyde, pyrrole-2-carbal-
dehyde, and p-tolualdehyde all reacted smoothly under the
standard conditions to give the expected quinolines 7a–f,
respectively (Scheme 7).
N
N
N
Fe
7a: 68%
7c: 52%
7b: 72%
N
N
N
N
S
H
We have established a novel protocol based on silver-
catalyzed sequential formation of two C–C bonds for the
construction of a series of polysubstituted quinolines from
anilines, aldehydes, and alcohols under mild conditions.
The transformation is effective for a broad range of sub-
strates, including aliphatic alcohols, arylalkanols, cycloal-
kanols, and ethylene glycol, thereby permitting the expan-
7d: 65%
7e: 78%
7f: 83%
Scheme 7 Scope of the reaction of ethylene glycol with aniline and
various aldehydes to give polysubstituted quinolines. Reaction condi-
tions: aniline (0.5 mmol), aldehyde 2 (0.5 mmol), ethylene glycol (0.75
mmol), AgOTf (0.025 mmol, 5 mol%), HOTf (0.05 mmol, 10 mol%), tol-
uene (2 mL), 120 °C, under air, 12 h. Yields of isolated products are re-
ported.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F

F
X. Zhang et al.
Letter
Synlett
ther investigations of the reaction’s scope, its detailed
mechanism, and its applications in organic synthesis are
ongoing in our laboratory.
(6) Bergstrom, F. W. Chem. Rev. 1944, 35, 77.
(7) Nitidandhaprabhas, O. Nature 1966, 212, 504.
(8) Born, J. L. J. Org. Chem. 1972, 37, 3952.
(9) Cragoe, E. J. Jr.; Robb, C. M. Org. Synth. Coll. Vol. V; Wiley:
London, 1973, 635.
(10) McNaughton, B. R.; Miller, B. L. Org. Lett. 2003, 5, 4257.
(11) (a) Jia, C.-S.; Zhang, Z.; Tu, S.-J.; Wang, G.-W. Org. Biomol. Chem.
2006, 4, 104. (b) Li, Z.; Xu, L.; Su, W. J. Chem. Res. 2011, 35, 240.
(12) Ji, X.; Huang, H.; Li, Y.; Chen, H.; Jiang, H. Angew. Chem. Int. Ed.
2012, 51, 7292.
(13) (a) Zhang, X.; Liu, B.; Shu, X.; Gao, Y.; Lv, H.; Zhu, J. J. Org. Chem.
2012, 77, 501. (b) Zhang, X.; Xu, X.; Yu, L.; Zhao, Q. Asian J. Org.
Chem. 2014, 3, 281. (c) Zhang, X.; Xu, X. Chem. Asian J. 2014, 9,
3089.
(14) (a) Li, H.; Wang, C.; Huang, H.; Xu, X.; Li, Y. Tetrahedron Lett.
2011, 52, 1108. (b) Li, H.; Xu, X.; Yang, J.; Xie, X.; Huang, H.; Li, Y.
Tetrahedron Lett. 2011, 52, 530. (c) Kong, L.; Zhou, Y.; Huang, H.;
Yang, Y.; Liu, Y.; Li, Y. J. Org. Chem. 2015, 80, 1275.
Acknowledgements
X.Z. gratefully acknowledges support from the National Natural Sci-
ence Foundation of China (21502100, 21302105) and the Research
Fund for the Key Scientific Research Program of Henan Educational
Committee (15A150021).
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561916.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(15) (a) Cai, S.; Zeng, J.; Bai, Y.; Liu, X.-W. J. Org. Chem. 2012, 77, 801.
(b) Fan, S.; Yang, J.; Zhang, X. Org. Lett. 2011, 13, 4374. (c) Patil,
N. T.; Raut, V. S. J. Org. Chem. 2010, 75, 6961. (d) Huo, Z.;
Gridnev, I. D.; Yamamoto, Y. J. Org. Chem. 2010, 75, 1266.
(e) Tobisu, M.; Hyodo, I.; Chatani, N. J. Am. Chem. Soc. 2009, 131,
12070. (f) Berman, A. M.; Lewis, J. C.; Bergman, R. G.; Ellman, J.
A. J. Am. Chem. Soc. 2008, 130, 14926. (g) Fleckenstein, C. A.;
Plenio, H. J. Org. Chem. 2008, 73, 3236. (h) Movassaghi, M.; Hill,
M. D. J. Am. Chem. Soc. 2006, 128, 4592. (i) Dagousset, G.; Zhu, J.;
Masson, G. J. Am. Chem. Soc. 2011, 133, 14804.
(16) (a) Potavathri, S.; Pereira, K. C.; Gorelsky, S. I.; Pike, A.; LeBris, A.
P.; DeBoef, B. J. Am. Chem. Soc. 2010, 132, 14676. (b) Rousseaux,
S.; Gorelsky, S. I.; Chung, B. K. W.; Fagnou, K. J. Am. Chem. Soc.
2010, 132, 10692. (c) Lafrance, M.; Fagnou, K. J. Am. Chem. Soc.
2006, 128, 16496.
References and notes
(1) (a) Michael, J. P. Nat. Prod. Rep. 2008, 25, 166. (b) Bax, B. D.;
Chan, P. F.; Eggleston, D. S.; Fosberry, A.; Gentry, D. R.; Gorrec,
F.; Giordano, I.; Hann, M. M.; Hennessy, A.; Hibbs, M.; Huang, J.;
Jones, E.; Jones, J.; Brown, K. K.; Lewis, C. J.; May, E. W.;
Saunders, M. R.; Singh, O.; Spitzfaden, C. E.; Shen, C.; Shillings,
A.; Theobald, A. J.; Wohlkonig, A.; Pearson, N. D.; Gwynn, M. N.
Nature 2010, 466, 935. (c) Ridley, R. G. Nature 2002, 415, 686.
(d) Rouffet, M.; de Oliveira, C. A. F.; Udi, Y.; Agrawal, A.; Sagi, I.;
McCammon, J. A.; Cohen, S. M. J. Am. Chem. Soc. 2010, 132,
8232. (e) Klingenstein, R.; Melnyk, P.; Leliveld, S. R.; Ryckebusch,
A.; Korth, C. J. Med. Chem. 2006, 49, 5300. (f) Natarajan, J. K.;
Alumasa, J. N.; Yearick, K.; Ekoue-Kovi, K. A.; Casabianca, L. B.;
de Dios, A. C.; Wolf, C.; Roepe, P. D. J. Med. Chem. 2008, 51, 3466.
(g) Lord, A.-M.; Mahon, M. F.; Lloyd, M. D.; Threadgill, M. D.
J. Med. Chem. 2009, 52, 868. (h) Andrews, S.; Burgess, S. J.;
Skaalrud, D.; Xu Kelly, J.; Peyton, D. H. J. Med. Chem. 2010, 53,
916. (i) Chen, Y.-L.; Zhao, Y.-L.; Lu, C.-M.; Tzeng, C.-C.; Wang, J.-
P. Bioorg. Med. Chem. 2006, 14, 4373. (j) Benedetti, P.;
Mannhold, R.; Cruciani, G.; Ottaviani, G. Bioorg. Med. Chem.
2004, 12, 3607. (k) Behenna, D. C.; Stockdill, J. L.; Stoltz, B. M.
Angew. Chem. Int. Ed. 2008, 47, 2365.
(2) (a) Yadav, J. S.; Subba Reddy, B. V.; Premalatha, K.; Murty, M. S.
R. J. Mol. Catal. A: Chem. 2007, 271, 161. (b) Mierde, H. V.; van
der Voort, P.; De Vos, D.; Verpoort, F. Eur. J. Org. Chem. 2008,
1625. (c) Zhang, Z.; Tan, J.; Wang, Z. Org. Lett. 2008, 10, 173.
(3) (a) Bhalla, V.; Vij, V.; Kumar, M.; Sharma, P. R.; Kaur, T. Org. Lett.
2012, 14, 1012. (b) Velusamy, M.; Chen, C.-H.; Wen, Y. S.; Lin, J.
T.; Lin, C.-C.; Lai, C.-H.; Chou, P.-T. Organometallics 2010, 29,
3912. (c) Tao, S.; Li, L.; Yu, J.; Jiang, Y.; Zhou, Y.; Lee, C.-S.; Lee, S.-
T.; Zhang, X.; Kwon, O. Chem. Mater. 2009, 21, 1284. (d) Kim, J. I.;
Shin, I.-S.; Kim, H.; Lee, J.-K. J. Am. Chem. Soc. 2005, 127, 1614.
(4) Marco-Contelles, J.; Pérez-Mayoral, E.; Samadi, A.; do Carmo
Carreiras, M.; Soriano, E. Chem. Rev. 2009, 109, 2652.
(17) 7-Methyl-3-phenyl-1,2-dihydrocyclobuta[c]quinoline (6a);
Typical Procedure
A 25 mL reaction tube was charged with 4-TolNH2 (0.5 mmol)
and PhCHO (0.5 mmol), and the mixture was stirred at 100 °C
for 5 min. Cyclobutanol (0.75 mmol, 1.5 equiv), AgOTf (0.025
mmol), HOTf (0.05 mmol), and toluene (2 mL) were added, and
the mixture was stirred at 120 °C for 12 h. The reaction was
quenched with sat. aq NaHCO3, and the mixture was diluted
with CH2Cl2 (10 mL) and washed with H2O (10 mL). The aqueous
layer was extracted with CH2Cl2 (2 × 10 mL), and the organic
phases were combined, dried (Na2SO4), and concentrated. The
residue was purified by chromatography [silica gel, hexane–
EtOAc (20:1)] to give a pale yellow solid; yield: 78.4 mg (64%);
mp 164–166 °C. 1H NMR (400 MHz, CDCl3): δ = 8.20 (d, J = 7.6
Hz, 2 H), 8.04 (d, J = 8.4 Hz, 1 H), 7.42–7.53 (m, 5 H), 3.64 (s, 2
H), 3.50 (m, 2 H), 2.53 (s, 3 H). 13C NMR (100 MHz, CDCl3):
δ = 151.8, 150.2, 146.3, 138.0, 136.4, 136.2, 130.9, 130.7, 129.3,
128.7, 127.5, 124.0, 120.8, 31.2, 29.3, 21.7. HRMS (EI): m/z [M+]
calcd for C18H15N: 245.1204; found 245.1205.
(18) See the Supporting Information for details. CCDC 1465172 con-
tains the supplementary crystallographic data for this paper.
The data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstruc-
tures.
(5) (a) Manske, R. H. F.; Kukla, M. Org. React. (N. Y.) 1953, 7, 59.
(b) Denmark, S. E.; Venkatraman, S. J. Org. Chem. 2006, 71, 1668.
(c) Theoclitou, M.-E.; Robinson, L. A. Tetrahedron Lett. 2002, 43,
3907. (d) Eisch, J. J.; Dluzniewski, T. J. Org. Chem. 1989, 54, 1269.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F