Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis of Azaquinolizinium Cations

Article abstract of DOI:10.1002/ejoc.201500404

A strategy based on a ring-closing metathesis (RCM) reaction of pyridinium azadienes in the presence of the second generation Grubbs catalyst was employed as a new approach to synthesize the 1-azaquinolizinium (pyrido[1,2-a]pyrimidin-5-ium) heterocycle and some simple derivatives. This method was also successfully applied to the first reported synthesis of the benzo-1-azaquinolizinium (pyrimido[2,1-a]isoquinolinium) cation by using the Hoveyda-Grubbs catalyst in Cl₂CHCHCl₂ at 130 C.

Full text of DOI:10.1002/ejoc.201500404

FULL PAPER
DOI: 10.1002/ejoc.201500404
Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis of
Azaquinolizinium Cations
Alberto Abengózar,[a] Beatriz Abarca,[a] Ana M. Cuadro,*[a] David Sucunza,[a]
Julio Álvarez-Builla,[a] and Juan J. Vaquero*[a]
Keywords: Synthetic methods / Nitrogen heterocycles / Metathesis / Ruthenium / Cations
A strategy based on a ring-closing metathesis (RCM) reaction
of pyridinium azadienes in the presence of the second gener-
ation Grubbs catalyst was employed as a new approach to
synthesize the 1-azaquinolizinium (pyrido[1,2-a]pyrimidin-5-
ium) heterocycle and some simple derivatives. This method
was also successfully applied to the first reported synthesis
of the benzo-1-azaquinolizinium (pyrimido[2,1-a]isoquinolin-
ium) cation by using the Hoveyda–Grubbs catalyst in
Cl2CHCHCl2 at 130 °C.
Introduction
The ruthenium-catalyzed ring-closing metathesis reac-
tion (RCM) has proven to be a very useful method for the
synthesis of medium-sized nitrogen-containing heterocy-
cles.[1] Studies in our laboratory have focused on the devel-
opment of RCM reactions for a new type of azinium azadi-
ene, and this approach has led to a new route for the prepa-
ration of azonia aromatic heterocycles such as quinolizin-
ium ions as well as benzo-, dibenzo-, and naphthoquinoliz-
inium cations from azinium salts in good overall yields un-
der mild reaction conditions[2] (Scheme 1).
These types of heteroaromatic cations contain a quater-
nary bridgehead nitrogen atom and are well-represented in
nature, as they form part of a wide range of alkaloids such
as coralyne, the vast family of berberines, and a family of
alkaloids based on the indolo[2,3-a]quinolizinium unit.[3] In
addition, some derivatives of these azonia salts have proven
useful in important applications such as cyanine dyes[4] and
highly fluorescent compounds that are used as probes for
the detection of biomolecules.[5] Furthermore, these com-
pounds have relevant biological activity as N-methyl-d-as-
partate (NMDA) antagonists,[6] activators of wild-type and
mutant cystic fibrosis transmembrane conductance regula-
tor (CFTR),[7] and inhibitors of protein kinase CKII.[8]
As a continuation of our work on this successful ap-
proach to the synthesis of azonia aromatic heterocycles, we
propose that the pyrido[1,2-a]pyrimidin-5-ium (1-azaquin-
olizinium) ion is the most suitable azaquinolizinium isomer
Scheme 1. Azonia aromatic heterocycles by RCM reactions (Cy =
cyclohexyl, Mes = mesitylene, G-II = second generation Grubbs
catalyst, H–G = Hoveyda–Grubbs catalyst).
to be constructed by an RCM reaction of the corresponding
azadiene.[9] Herein, we report our results on the syntheses
of new pyridinium azadienes under RCM reaction condi-
tions, which allow for an alternative synthesis of the pyr-
ido[1,2-a]pyrimidin-5-ium (1-azaquinolizinium) system and,
for the first time, the synthesis of the pyrimido[2,1-a]iso-
quinolinium (benzo-1-azaquinolizinium) heterocycle from
isoquinolinium azadienes.
[a] Departamento de Química Orgánica y Química Inorgánica,
Universidad de Alcalá,
The three possible dienes to produce 1-azaquinolizium
ion 1a through the key RCM reaction are presented in
Scheme 2. Strategy a clearly resembles dienes that have been
used in quinolizinium syntheses, whereas strategies b and c
are limited by the formation of the corresponding dienes
from a 2-substituted pyrimidine.
28871 Alcalá de Henares, Madrid, Spain
E-mail: ana.cuadro@uah.es
juanjose.vaquero@uah.es
http://www.uah.es/gi/QUIBIO
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201500404.
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Azonia Aromatic Cations by Ring-Closing Metathesis
Scheme 2. RCM reactions for the synthesis of 1-azaquinolizinium
cation (1a).
The synthesis of 1a would involve the preparation of pro-
tected key diene intermediate 6a, which may be readily
available from the corresponding N-protected propen-
ylamino pyridine 4a. Compound 4a could be obtained from
commercially available 2-aminopyridine (Scheme 3).
Scheme 4. Synthesis of 1a (DMF = N,N-dimethylformamide, OTf
= trifluoromethanesulfonate, TFA = trifluoroacetic acid).
The dehydrohalogenation of 5a to produce 6a was also
attempted by exploring conditions that proved successful
for the syntheses of N-vinyl analogues employed in the
preparation of quinolizinium and benzoquinolizinium cat-
ions. Thus, in the presence of Cs2CO3 as the base and by
using different mixtures of CH3CN/iPrOH as the solvent,
compound 5a afforded the diene, which was accompanied
by decomposition products. This made isolation and purifi-
cation of the target compound difficult. Better results were
obtained by using NaOH as the base,[13] and the best yield
was achieved in a 3:1 mixture of EtOH/MeOH at –10 °C
with careful control of the concentration of the base (lower
than 0.05 m). Under these conditions, 6a was obtained in
68% yield.
On the basis of our experience with the formation of di-
hydroquinolizinium systems by RCM reactions, the cycliza-
tion of 6a was attempted in the presence of Grubbs II[14]
and Hoveyda–Grubbs catalysts.[15] Although the Hoveyda–
Grubbs catalyst has led to better yields in most of the RCM
reactions that we have conducted, very similar yields were
Scheme 3. Retrosynthesis for 1a (PG = protecting group).
The first synthesis of a 1-azaquinolizinium system was
reported by Nesmeyanov and co-workers and also started
from 2-aminopyridine, which was condensed with 1,3-dicar-
bonyl compounds under strongly acidic conditions to afford
simple derivatives in variable yields.[10] On the basis of this
procedure, in which the bicyclic ring is built from the for-
mation of the C-4–N-5 bond, Pollack and co-workers re-
ported the first and only synthesis of 1-azaquinolizinium
bromide by using the condensation reaction of 2-aminopyr-
idine and malonaldehyde bis(diethyl acetal).[11]
Results and Discussion
Our synthetic route involves the formation of the C-3– obtained by both catalysts in this case. Under the best con-
C-4 bond to give the pyrimidinium ring and began from 2- ditions (CH2Cl2, 40 °C) and by heating the reaction mixture
aminopyridine (2a, Scheme 4), which was initially protected for 4 h, RCM product 7a was obtained in 60%. Finally,
as tert-butylcarbamate 3a (Boc = tert-butoxycarbonyl) ac- deprotection of 7a produced the corresponding 1,2-dihydro-
cording to a literature procedure.[12] The reaction of 3a with 1-azaquinolizinium triflate 8a, which was oxidized by heat-
allyl bromide in the presence of sodium hydride afforded 4a ing at 200 °C in the presence of Pd/C (10%) without solvent
in 60% yield. Various conditions and bases were examined to give the 1-azaquinolizinium triflate (1a) in a high yield.
in an attempt to improve the yield, but all were unsuccess-
Notably, the formation of a pyrimidine ring by an RCM
ful. Deprotection or the formation of complex reaction reaction is unprecedented. Moreover, this is the first route
mixture was observed. We proceeded with the preparation to allow for the synthesis of the parent 1,2-dihydro-1-aza-
of diene 6a by using our previously reported procedure for quinolizinium system (8a) in a synthetically useful overall
the synthesis of quinolizinium ions.[2] Thus, the reaction of yield, which enabled its first full characterization.
4a with freshly prepared 2-chloroethyl triflate in CCl4 at
Our next step was to study the scope of the RCM reac-
room temperature afforded the desired pyridinium salt 5a, tion and produce various substituted 1-azaquinolizinium
albeit in only 35% yield. This yield was improved to 60% derivatives by using the appropriate dienic pyridinium salts
by carrying out the reaction at 70 °C for 16 h.
as substrates for the RCM reaction. 1-Aminoisoquinoline
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A. M. Cuadro, J. J. Vaquero et al.
FULL PAPER
and 2-aminoquinoline were also explored as heterocyclic Table 2. Synthesis of azinium salts 5.
templates for conversion into the appropriate isoquinolin-
ium and quinolinium dienes, which would lead to new pyri-
mido[2,1-a]isoquinolinium and pyrimido[1,2-a]quinolinium
derivatives, respectively. Commercially available aminoazine
derivatives were used as starting materials to obtain the cor-
responding N-Boc-protected derivatives 3b–3g by using the
same conditions as employed for the protection of 2-amino-
pyridine. The N-alkylation of the exocyclic nitrogen was
subsequently carried out with allyl bromide under the same
conditions as used for the preparation of 4a. The results are
summarized in Table 1 and show that compounds 4b–4g
were obtained in good to excellent overall yields. 4-Methoxy
derivative 4h was also synthesized but by using an alterna-
tive method (Scheme 5). In this case, 2-allylaminopyridine
9 was prepared from the corresponding pyridine N-oxide
by following a procedure developed by Londregan and co-
workers.[16] The subsequent protection of 9 with a Boc
group afforded the desired derivative 4h in 68% overall
yield.
Table 1. Synthesis of propenylamino azine derivatives 4b–4g.
[a] At 70 °C. [b] n.r.: no reaction. [c] At room temperature. [d] dec.:
decomposition.
Scheme 5. Synthesis of 4h (PyBroP = bromotripyrrolidinophos-
phonium hexafluorophosphate).
Unfortunately, the N-alkylation reactions of derivatives salts under the same conditions, and the starting materials
4b–4h with chloroethyl triflate to form the corresponding were recovered. Under more forcing conditions, extensive
pyridinium salts were troublesome, and of the monocyclic decomposition of the 2-chloroethyl triflate was observed
pyridine derivatives (i.e, 4b–4e and 4h), only those with elec- without the formation of the corresponding pyridinium
tron-donating substituents (i.e, 4b, 4e, and 4h) underwent salts. In the case of propenylisoquinoline derivative 4f, the
the N-alkylation reaction in good yields (Table 2). Thus, N-alkylation reaction afforded the expected isoquinolinium
pyridinium salts 5b, 5e, and 5h were obtained the high salt 5f in good yield at room temperature. However, under
yields of 83, 76, and 87%, respectively, by carrying out the the same conditions, the reaction of quinoline derivative 4g
reaction at 70 °C. Derivatives 4c and 4d, which have elec- did not proceed. At higher temperatures, deprotection of
tron-withdrawing substituents, did not give the pyridinium the amino group was observed for both the isoquinoline
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Azonia Aromatic Cations by Ring-Closing Metathesis
and quinoline derivatives. The resulting 1-propenylami- Table 3. Synthesis of diene 6f and yields of the RCM reaction.
noisoquinoline and 2-propenylaminoquinoline were treated
with 2-chloroethyl triflate at 70 °C, which resulted in a reac-
tion at the exocyclic nitrogen atom and gave the corre-
sponding tertiary amines. In the case of the isoquinoline
derivative, this could be isolated as a byproduct.
The desired 1-azaquinolizinium derivatives 1b, 1e, and 1h
were obtained by following the sequence of reactions pre-
viously described for the synthesis of parent 1a. However,
the dehydrohalogenation of 5b, 5e, and 5h required different
reaction conditions to obtain a good yield, as 5b, 5e, and
5h were unreactive in the presence of NaOH under the con-
ditions employed for 5a. Fortunately, high yields were
achieved by using Cs2CO3 in CH3CN/iPrOH. The best con-
ditions and yields obtained for each step are shown in
Scheme 6 .[17]
Entry Catalyst
Conditions
Yield [%]
1
2
3
4
5
6
7
8
G-II (5 mol-%)
G-II (5 mol-%)
H–G (5 mol-%)
CH2Cl2, room temp., 6 h
CH2Cl2, 40 °C, 6 h
CH2Cl2, 40 °C, 2.5 h
0
10[a]
21[a]
25[a]
47[b]
60[b]
61[c]
56[c]
H–G (10 mol-%) CH2Cl2, 40 °C, 5 h
H–G (5 mol-%)
H–G (5 mol-%)
H–G (5 mol-%)
H–G (5 mol-%)
ClCH2CH2Cl, 80 °C, 3 h
Cl2CHCHCl2, 130 °C, 2 h
Cl2CHCHCl2, 130 °C, 4 h
Cl2CHCHCl2, 130 °C, 6 h
[a] Isolated yields of compound 7f. [b] Determined yields of 7f in
the mixture 7f/8f. [c] Isolated yield of 8f.
Scheme 7. Synthesis of the pyrimido[2,1-a]isoquinolinium triflate
(1f).
Scheme 6. Synthesis of 9-methyl, 7-phenyl-, and 8-methoxy-1-aza-
quinolizinium derivatives.
Conclusions
We have applied a new approach for the synthesis of the
pyrimido[1,2-a]pyrimidin-5-ium (1-azaquinolizinium) het-
erocycle and some simple derivatives. This route is based on
an unprecedented RCM reaction for the construction of the
pyrimidinium ring. This strategy also allowed access to the
parent pyrimido[2,1-a]isoquinolinium heterocycle for the
first time.
The dehydrohalogenation of 5f to produce 6f was
achieved in the presence of NaOH under the conditions em-
ployed for 5a. However, when the conditions for the RCM
reactions were applied to dienic isoquinolium salt 6f, the
expected tricyclic product was not formed. After exploring
different conditions, we found that the Hoveyda–Grubbs
catalyst promoted the cyclization reaction more efficiently
than the second generation Grubbs catalyst. Better yields
were obtained by increasing the reaction temperature, but
the formation of 7f was accompanied by variable amounts
of 1,2-dihydropyrimido[2,1-a]isoquinolinium triflate (8f) as
a result of deprotection. The mixture of 7f and 8f was diffi-
cult to separate, and the reaction time was therefore pro-
longed until 8f was the only product. The conditions and
results are summarized in Table 3.
Experimental Section
General Methods: Infrared spectra were recorded as KBr or NaCl
pellets, and the spectral bands were reported in cm–1. The 1H NMR
spectroscopic data were recorded at 200, 300, and 500 MHz, and
the 13C NMR spectroscopic data were recorded at 50, 75, and
125 MHz. Chemical shifts were reported as δ values (ppm). The
mass spectra were obtained by ESI+ and DIP/IQ. Ruthenium cata-
lysts G-II and H–G, 2-aminopyridines 2a–2c, 1-aminoisoquinoline
(2f), and 2-aminoquinoline (2g) were purchased from Aldrich and
used without further purification. The 2-amino-4-nitropyridine
(2d),[18] 2-amino-5-phenylpyridine (2e),[19] and 4-methoxypyridine
Finally, dihydro compound 8f was oxidized to give
pyrimido[2,1-a]isoquinolinium triflate (1f) under the same
conditions that were used for the oxidation of the 1-azaqui-
nolizinium cation and its derivatives to afford the parent N-oxide[20] were prepared by following the literature procedure.
heterocycle in 77% yield (Scheme 7). It is noteworthy that
General Procedure for the Synthesis of (tert-Butoxycarbonyl)amino
1f has not been previously reported, and this strategy, which
is based on an RCM to construct the pyrimidine ring, al-
lowed its synthesis in 16% overall yield.
Derivatives 3: To a solution of (Boc)2O (1 or 1.8 equiv.) in tert-
butanol (35 mL) was slowly added the corresponding aminoazine
(5.3 mmol), and the mixture was stirred at room temperature until
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A. M. Cuadro, J. J. Vaquero et al.
FULL PAPER
the starting material was consumed. The solvent was evaporated
under reduced pressure, and the residue was purified by flash col-
umn chromatography on silica gel to give the corresponding N-
Boc-protected derivative 3.
column chromatography (hexane/EtOAc, 7:3) to give 3f (0.953 g,
3.90 mmol, 74%) as a colorless oil. IR (NaCl): ν
= 3345, 2924,
˜
max
1589, 1379, 1122, 1031, 796 cm–1. 1H NMR (300 MHz, [D6]acet-
one): δ = 8.67 (br. s, 1 H), 8.25 (d, J = 5.6 Hz, 1 H), 8.15 (d, J =
8.1 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.73 (t, J = 7.2 Hz, 1 H),
7.62 (m, 2 H), 1.49 (s, 9 H) ppm. 13C NMR (75 MHz, [D6]acetone):
δ = 157.9, 142.4, 138.3, 130.6, 127.4, 126.4, 124.3, 118.5, 111.6,
81.2, 28.1 ppm. HRMS (ESI+): calcd. for C14H16N2O2 [M + H]+
245.1290; found 245.1283.
2-(N-tert-Butoxycarbonylamino)pyridine (3a): By following the ge-
neral procedure, 2-aminopyridine (2a, 0.5 g, 5.31 mmol) and
(Boc)2O (1.16 g, 5.31 mmol) afforded the crude residue, which was
purified by flash column chromatography (hexane/EtOAc, 6:1) to
give 3a (0.843 g, 4.34 mmol, 82%) as a white powder, m.p. 93–
94 °C; ref.[12a] m.p. 92–93 °C.
2-(N-tert-Butoxycarbonylamino)quinoline (3g): By following the ge-
neral procedure, 2g (605 mg, 4.20 mmol) and (Boc)2O (916 mg,
4.20 mmol) afforded the crude product, which was purified by flash
chromatography (hexane/EtOAc, 8:2) to give 3g (773 mg,
3.16 mmol, 75%) as a white powder; m.p. 161–163 °C. IR (KBr):
2-(N-tert-Butoxycarbonylamino)-3-methylpyridine (3b): By follow-
ing the general procedure, 2b (0.6 g, 5.55 mmol) and (Boc)2O
(1.21 g, 5.55 mmol) afforded the crude product, which was purified
by flash column chromatography (hexane/EtOAc , 8:2) to give 3b
(0.871 g, 4.18 mmol, 75%) as a white powder; m.p. 138–140 °C. IR
ν
˜
max = 2983, 1812, 1606, 1329, 1159, 1068, 845, 775 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 8.18 (d, J = 9.1 Hz, 1 H), 8.10 (d, J =
9.1 Hz, 1 H), 7.87 (br. s, 1 H), 7.78 (d, J = 8.9 Hz, 1 H), 7.73 (dd,
J = 1.0, 8.2 Hz, 1 H), 7.64–7.59 (m, 1 H), 7.41–7.36 (m, 1 H), 1.50
(s, 9 H) ppm. 13C NMR (50 MHz, [D6]acetone): δ = 152.6, 151.4,
146.5, 138.4, 129.8, 127.5, 127.1, 125.7, 124.7, 113.0, 81.2,
28.2 ppm. HRMS (ESI+): calcd. for C14H16N2O2 [M + H]+
245.1285; found 245.1281.
(KBr): ν
= 3205, 2976, 1724, 1526, 1172, 795 cm–1. 1H NMR
˜
max
(200 MHz, CD3OD): δ = 8.22 (d, J = 4.8 Hz, 1 H), 7.71 (dd, J =
0.9, 7.5 Hz, 1 H), 7.20 (dd, J = 4.8, 7.5 Hz, 1 H), 2.31 (s, 3 H), 1.55
(s, 9 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 146.5, 141.3,
130.2, 122.8, 81.4, 28.6, 17.6 ppm. MS (ESI+): m/z (%) = 209 (100)
[M]+. C11H16N2O2 (208.26): calcd. C 63.44, H 7.74, N 13.45; found
C 63.33, H 7.56, N 13.60.
General Procedure for the Synthesis of N-Propenylamino-Substi-
tuted Azines 4: Sodium hydride (60% dispersion in mineral oil,
127 mg, 3.17 mmol) was added to a solution of the corresponding
azine derivative 3 (2.11 mmol) in dry DMF (30 mL), and the re-
sulting mixture was stirred at 0 °C for 30 min. Propenyl bromide
(387 mg, 227 μL, 3.17 mmol) was added, and the stirring was con-
tinued for 30 min. The reaction mixture was warmed to room tem-
perature and then stirred at this temperature for 2 h. The mixture
was washed with water (20 mL) and extracted with EtOAc (3ϫ
20 mL). The combined organic layers were dried with MgSO4, fil-
tered, and concentrated under reduced pressure. The residue was
purified by flash column chromatography on silica gel (hexane/
EtOAc, 8:2) to give the corresponding N-propenylamino-substi-
tuted azine 4.
2-(N-tert-Butoxycarbonylamino)-5-bromopyridine (3c): By following
the general procedure, 2c (1.0 g, 5.78 mmol) and (Boc)2O (1.26 g,
5.78 mmol) afforded the crude product, which was purified by flash
column chromatography (hexane/EtOAc, 9:1) to give 3c (0.694 g,
2.54 mmol, 44%) as a white powder; m.p. 173–175 °C. IR (KBr):
ν
=
3210, 2972, 2315, 1719, 1407, 830 cm–1. 1H NMR
˜
max
(200 MHz, CD3OD): δ = 8.30 (s, 1 H), 7.86 (s, 2 H), 1.56 (s, 9
H) ppm. 13C NMR (50 MHz, [D6]acetone): δ = 152.6, 149.3, 141.2,
114.4, 113.2, 81.2, 28.4 ppm. MS (ESI+): m/z (%) = 273 (31) [M]+,
275 (30) [M + 2]+, 219 (95), 217 (100). C10H13BrN2O2 (273.13):
calcd. C 43.98, H 4.80, N 10.26; found C 43.76, H 4.96, N 10.28.
2-(N-tert-Butoxycarbonylamino)-4-nitropyridine (3d): By following
the general procedure, 2d[18] (0.737 g, 5.30 mmol) and (Boc)2O
(1.16 g, 5.30 mmol) afforded the crude product, which was purified
by flash column chromatography (hexane/EtOAc, 8:2) to give 3d
(0.354 g, 1.48 mmol, 28%) as a yellow powder; m.p. 158–160 °C.
2-(N-Allyl-N-tert-butoxycarbonylamino)pyridine (4a): By following
the general procedure, 3a (500 mg, 2.57 mmol) led to 4a (362 mg,
1.55 mmol, 60%) as a yellow oil. IR (NaCl): ν
= 2954, 1715,
˜
max
1589, 1469, 1379, 1145, 740 cm–1. H NMR (300 MHz, CD3OD):
δ = 8.40–8.38 (m, 1 H), 7.80 (td, J = 2.0, 8.2 Hz, 1 H), 7.56 (dd, J
= 1.0, 8.2 Hz, 1 H), 7.21–7.17 (m, 1 H), 6.00–5.88 (m, 1 H), 5.19–
5.08 (m, 2 H), 4.50 (dt, J = 1.3, 5.6 Hz, 2 H), 1.51 (s, 9 H) ppm.
13C NMR (50 MHz, [D6]acetone): δ = 147.4, 137.0, 136.8, 135.1,
119.3, 119.1, 115.3, 109.9, 80.6, 48.5, 27.3 ppm. MS (ESI+): m/z
(%) = 235 (100) [M]+. C13H18N2O2 (234.30): calcd. C 66.64, H 7.74,
N 11.96; found C 66.55, H 7.62, N 12.03. Compound was pre-
viously reported.[21]
1
IR (KBr): ν
= 3418, 2983, 1737, 1615, 1554, 1421, 1347, 1278,
˜
max
1150, 741 cm–1. 1H NMR (300 MHz, CDCl3): δ = 8.71 (d, J =
2.0 Hz, 1 H), 8.48 (d, J = 5.5 Hz, 1 H), 8.12 (s, 1 H), 7.64 (dd, J =
2.0, 5.5 Hz, 1 H), 1.54 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3):
δ = 155.6, 154.4, 151.9, 149.7, 110.9, 105.6, 82.3, 28.2 ppm. HRMS
(ESI+): calcd. for C10H13N3O4 [M + H]+ 240.0984; found 240.0978.
2-(N-tert-Butoxycarbonylamino)-5-phenylpyridine (3e): By following
the general procedure, 2e (0.500 g, 2.94 mmol) and (Boc)2O (1.15 g,
5.29 mmol) afforded the crude product, which was purified by flash
column chromatography (hexane/EtOAc, 9:1) to give 3e (0.667 g,
2.48 mmol, 84%) as a white powder; m.p. 169–171 °C. IR (KBr):
2-(N-Allyl-N-tert-butoxycarbonylamino)-3-methylpyridine (4b): By
following the general procedure, 3b (500 mg, 2.40 mmol) led to 4b
ν
= 3190, 2976, 1717, 1595, 1526, 1252, 1156, 1061, 771,
˜
(471 mg, 1.90 mmol, 79%) as a yellow oil. IR (NaCl): νmax = 3395,
max
˜
697 cm–1. H NMR (300 MHz, CDCl3): δ = 8.50 (d, J = 2.3 Hz, 1
H), 8.11 (br. s, 1 H), 8.02 (d, J = 8.7 Hz, 1 H), 7.86 (dd, J = 2.3,
8.7 Hz, 1 H), 7.55–7.52 (m, 2 H), 7.46–7.41 (m, 2 H), 7.37–7.32 (m,
1 H), 1.52 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.5,
151.2, 146.0, 137.6, 136.7, 131.6, 129.0, 127.5, 126.7, 112.1, 81.0,
28.3 ppm. MS (ESI+): m/z (%) = 215 (54), 271 (100) [M]+.
C16H18N2O2 (270.33): calcd. C 71.09, H 6.71, N 10.36; found C
70.70, H 6.63, N 10.00.
1
1
2977, 1705, 1576, 1454, 1152, 923 cm–1. H NMR (200 MHz, [D6]-
acetone): δ = 8.26 (dd, J = 1.6, 4.7 Hz, 1 H), 7.64 (d, J = 7.5 Hz,
1 H), 7.16 (dd, J = 4.7, 7.5 Hz, 1 H), 6.00–5.80 (m, 1 H), 5.10–5.01
(m, 2 H), 4.31 (br. s, 2 H), 2.22 (s, 3 H), 1.39 (s, 9 H) ppm. 13C
NMR (50 MHz, [D6]acetone): δ = 154.0, 153.8, 146.1, 138.9, 134.5,
131.1, 122.1, 116.3, 79.6, 50.9, 27.5, 16.9 ppm. MS (ESI+): m/z (%)
= 249 (42) [M]+, 193 (100). C14H20N2O2 (248.33): calcd. C 67.72,
H 8.12, N 11.28; found C 67.53, H 8.23, N 11.18.
2-(N-tert-Butoxycarbonylamino)isoquinoline (3f): By following the 2-(N-Allyl-N-tert-butoxycarbonylamino)-5-bromopyridine (4c): By
general procedure, 2f (0.764 g, 5.30 mmol) and (Boc)2O (1.16 g,
5.30 mmol) afforded the crude product, which was purified by flash
following the general procedure, 3c (500 mg, 1.83 mmol) led to 4c
(504 mg, 1.61 mmol, 88%) as a yellow oil. IR (NaCl): νmax = 3082,
˜
4218
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4214–4223

Azonia Aromatic Cations by Ring-Closing Metathesis
1
2929, 1713, 1464, 1387, 1247, 774 cm–1. H NMR (300 MHz, [D6]-
ν
˜
= 2978, 1708, 1595, 1570, 1481, 1382, 1248, 1147, 1031,
max
acetone): δ = 8.40 (d, J = 2.4 Hz, 1 H), 7.90–7.86 (m, 1 H), 7.78 757 cm–1. H NMR (300 MHz, CDCl3): δ = 8.10 (d, J = 5.9 Hz, 1
(d, J = 8.9 Hz, 1 H), 5.99–5.86 (m, 1 H), 5.14–5.04 (m, 2 H), 4.55 H), 7.20 (d, J = 2.2 Hz, 1 H), 6.51 (dd, J = 2.2, 5.9 Hz, 1 H), 5.95–
(d, J = 5.5 Hz, 2 H), 1.50 (s, 9 H) ppm. 13C NMR (50 MHz, [D6]- 5.82 (m, 1 H), 5.08 (dd, J = 1.6, 17.1 Hz, 1 H), 5.02 (dd, J = 1.6,
1
acetone): δ = 153.9, 148.5, 140.1, 135.3, 120.9, 116.2, 114.8, 81.8,
10.3 Hz, 1 H), 4.49 (dt, J = 1.6, 5.3 Hz, 2 H), 3.76 (s, 3 H), 1.44 (s,
49.1, 28.2 ppm. MS (ESI+): m/z (%) = 315 (35) [M + 2]+, 313 (100) 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 166.3, 155.7, 153.8,
[M]+. C13H17BrN2O2 (313.20): calcd. C 49.86, H 5.47, N 8.94;
found C 49.75, H 5.58, N 8.97.
148.1, 134.6, 115.5, 106.9, 104.0, 80.9, 55.0, 48.9, 28.1 ppm. HRMS
(ESI+): calcd. for C14H21N2O3 [M + H]+ 265.1547; found 265.1541.
2-(N-Allyl-N-tert-butoxycarbonylamino)-4-nitropyridine (4d): By
following the general procedure, 3d (500 mg, 2.09 mmol) led to 4d
General Procedure for the Synthesis of N-(2-Chloroethyl)azinium
Triflates 5: To a solution of 2-chloroethanol (105 mg, 84 μL,
1.30 mmol) in dry CCl4 (1 mL) under argon was added dry pyridine
(103 mg, 106 μL, 1.30 mmol), and the mixture was stirred at room
temperature for 5–10 min. The mixture was added dropwise (5–
10 min) to a cooled solution (–10 °C) of triflic anhydride (352 mg,
209 μL, 1.30 mmol) in dry CCl4 (1.5 mL). The resulting mixture
was filtered through Na2SO4, and the solution was added by can-
nula to a solution of the N-propenylamino-substituted azine 4
(0.96 mmol) in dry CCl4 (1.5 mL). The mixture was stirred at room
temperature or at 70 °C for 24 h, and the solvent was then evapo-
rated under reduced pressure. The residue was purified by flash
column chromatography on silica gel to give the azinium salt.
(584 mg, 2.09 mmol, 100%) as a yellow oil. IR (NaCl): νmax = 3583,
˜
3134, 3084, 2979, 1715, 1537, 1378, 1238, 1148, 687 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 8.63 (d, J = 1.9 Hz, 1 H), 8.55 (d, J =
5.6 Hz, 1 H), 7.64 (dd, J = 1.9, 5.6 Hz, 1 H), 5.99–5.87 (m, 1 H),
5.14 (dq, J = 1.3, 17.2 Hz, 1 H), 5.11 (dq, J = 1.3, 10.2 Hz, 1 H),
4.63 (dt, J = 1.3, 5.3 Hz, 2 H), 1.53 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 155.8, 154.2, 153.0, 148.7, 133.4, 115.9,
110.8, 110.5, 82.2, 48.3, 27.7 ppm. HRMS (ESI+): calcd. for
C13H18N3O4 [M + H]+ 280.1292; found 280.1281.
2-(N-Allyl-N-tert-butoxycarbonylamino)-5-phenylpyridine (4e): By
following the general procedure, 3e (571 mg, 2.11 mmol) led to 4e
(655 mg, 2.11 mmol, 100%) as a yellow oil. IR (NaCl): νmax = 3081,
˜
2-(N-Allyl-N-tert-butoxycarbonylamino)-1-(2-chloroethyl)pyrid-
inium Triflate (5a): By following the general procedure, the reaction
mixture of 4a (225 mg, 0.96 mmol) was heated at 70 °C. Purifica-
tion by chromatography (CH2Cl2/MeOH, 9.5:0.5) gave 5a (257 mg,
2976, 2924, 1715, 1599, 1473, 1381, 1240, 1179, 1156 cm–1. 1H
NMR (300 MHz, CDCl3): δ = 8.58 (dd, J = 0.8, 2.5 Hz, 1 H), 7.82
(dd, J = 2.5, 8.7 Hz, 1 H), 7.75 (dd, J = 0.8, 8.7 Hz, 1 H), 7.56–
7.52 (m, 2 H), 7.47–7.41 (m, 2 H), 7.38–7.33 (m, 1 H), 6.04–5.92 (m,
1 H), 5.17 (dq, J = 1.6, 17.1 Hz, 1 H), 5.11 (dq, J = 1.6, 10.3 Hz, 1
H), 4.60 (dt, J = 1.6, 5.3 Hz, 2 H), 1.51 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 154.1, 153.5, 145.6, 137.6, 135.4, 134.6,
132.2, 129.0, 127.6, 127.0, 119.0, 115.7, 81.3, 49.0, 28.2 ppm. MS
(ESI+): m/z (%) = 311 (85) [M]+, 255 (100). C19H22N2O2 (310.40):
calcd. C 73.52, H 7.14, N 9.03; found C 74.50, H 6.61, N 9.52.
0.58 mmol, 60%) as a pale yellow oil. IR (NaCl): ν
= 3584,
˜
max
2981, 1747, 1515, 774 cm–1. 1H NMR (300 MHz, CDCl3): δ = 9.08
(dd, J = 1.6, 6.2 Hz, 1 H), 8.62–8.58 (m, 1 H), 8.03–7.98 (m, 1 H),
7.85 (d, J = 8.1 Hz, 1 H), 5.98–5.85 (m, 1 H), 5.26 (d, J = 10.0 Hz,
1 H), 5.24 (d, J = 16.8 Hz, 1 H), 5.02–4.97 (m, 1 H), 4.82–4.69 (m,
1 H), 4.47 (dd, J = 5.0, 15.3 Hz, 1 H), 4.06–3.94 (m, 3 H), 1.40 (s,
9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 152.1, 150.4, 148.5,
146.6, 130.6, 128.4, 126.9, 121.4, 120.5 (q, J = 320.0 Hz), 85.1, 57.3,
53.0, 41.5, 27.8 ppm. MS (ESI+): m/z (%) = 299 (21) [M + 2]+, 297
(63) [M]+, 241 (100). C16H22ClF3N2O5S (446.87): C 43.00, H 4.96,
N 6.27, S 7.18; found C 42.75, H 5.22, N 6.17, S 7.23.
1-(N-Allyl-N-tert-butoxycarbonylamino)isoquinoline (4f): By follow-
ing the general procedure, 3f (500 mg, 2.05 mmol) led to 4f
(497 mg, 1.75 mmol, 85%) as a yellow oil. IR (NaCl): νmax = 3056,
˜
2978, 1704, 1498, 1366, 1147, 983 cm–1. 1H NMR (300 MHz,
CDCl3): δ = 8.36 (d, J = 5.6 Hz, 1 H), 7.94 (d, J = 8.6 Hz, 1 H),
7.81 (d, J = 7.6 Hz, 1 H), 7.66 (m, J = 1.3, 7.6 Hz, 1 H), 7.60–7.55
(m, 2 H), 6.01–5.87 (m, 1 H), 5.12 (dd, J = 1.3, 17.1 Hz, 1 H), 4.99
2-(N-Allyl-N-tert-butoxycarbonylamino)-1-(2-chloroethyl)-3-methyl-
pyridinium Triflate (5b): By following the general procedure, the
reaction mixture of 4b (238 mg, 0.96 mmol) was heated at 70 °C.
Purification by chromatography (CH2Cl2/MeOH, 9.5:0.5) gave 5b
(dd, J = 1.3, 10.2 Hz, 1 H), 4.50 (br. s, 2 H), 1.27 (s, 9 H) ppm. 13
C
NMR (75 MHz, CDCl3): δ = 154.4, 154.1, 141.2, 137.8, 133.9,
130.2, 127.3, 126.8, 126.1, 125.5, 120.4, 117.5, 80.8, 51.6, 28.0 ppm.
HRMS (ESI+): calcd. for C17H21N2O2 [M + H]+ 285.1603; found
285.1613.
(366 mg, 0.79 mmol, 83%) as a yellow oil. IR (NaCl): νmax = 3508,
˜
2981, 1732, 1616, 1260, 1151, 1031, 939 cm–1. 1H NMR (300 MHz,
[D6]acetone): δ = 9.13 (d, J = 6.2 Hz, 1 H), 8.78 (d, J = 8.0 Hz, 1
H), 8.20 (dd, J = 6.2, 8.0 Hz, 1 H), 6.17–6.08 (m, 1 H), 5.39–5.30
(m, 2 H), 5.24 (d, J = 10.1 Hz, 1 H), 5.02 (br. s, 1 H), 4.45 (dd, J
= 6.6, 14.6 Hz, 1 H), 4.38–4.36 (m, 2 H), 4.17 (br. s, 1 H), 2.55 (s,
3 H), 1.40 (s, 9 H) ppm. 13C NMR (75 MHz, [D6]acetone): δ =
151.5, 149.4, 146.5, 140.6, 132.2, 127.4, 122.2 (q, J = 321.9 Hz),
121.8, 121.6, 84.7, 59.1, 52.5, 42.6, 27.9, 18.0 ppm. HRMS (ESI+):
calcd. for C16H24ClN2O2 [M]+ 311.1526; found 311.1528.
2-(N-Allyl-N-tert-butoxycarbonylamino)quinoline (4g): By following
the general procedure, 3g (500 mg, 2.05 mmol) led to 4g (584 mg,
2.05 mmol, 100%) as a yellow oil. IR (NaCl): ν
= 3404, 2978,
˜
max
1713, 1602, 1504, 1429, 1330, 1239, 1143, 825, 622 cm–1. H NMR
(300 MHz, CDCl3): δ = 8.02 (d, J = 8.9 Hz, 1 H), 7.89 (d, J =
8.6 Hz, 1 H), 7.80 (d, J = 8.9 Hz, 1 H), 7.73 (d, J = 7.2 Hz, 1 H),
7.62 (td, J = 1.3, 7.2 Hz, 1 H), 7.45–7.40 (m, 1 H), 6.08–5.95 (m,
1 H), 5.19 (dd, J = 1.6, 17.1 Hz, 1 H), 5.08 (dd, J = 1.6, 10.2 Hz,
1 H), 7.71 (d, J = 5.6 Hz, 2 H), 1.51 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 154.2, 153.7, 146.6, 136.4, 134.7, 129.3,
128.3, 127.1, 125.7, 125.3, 118.9, 116.1, 81.4, 49.3, 28.2 ppm.
HRMS (ESI+): calcd. for C17H21N2O2 [M + H]+ 285.1598; found
285.1600.
1
2-(N-Allyl-N-tert-butoxycarbonylamino)-1-(2-chloroethyl)-5-phen-
ylpyridinium Triflate (5e): By following the general procedure, the
reaction mixture of 4e (183 mg, 0.59 mmol) was heated at 70 °C.
Purification by chromatography (CH2Cl2/MeOH, 9.5:0.5) gave 5e
(234 mg, 0.45 mmol, 76%) as a yellow oil. IR (NaCl): νmax = 3066,
˜
3015, 2982, 1733, 1532, 1372, 1260, 1225, 1155, 1031, 759,
1
638 cm–1. H NMR (300 MHz, CDCl3): δ = 9.16 (d, J = 2.2 Hz, 1
2-(N-Allyl-N-tert-butoxycarbonylamino)-4-methoxypyridine (4h): By
following the general procedure, 9 (310 mg, 1.89 mmol) and
H), 8.70 (dd, J = 2.2, 8.4 Hz, 1 H), 7.91 (d, J = 8.4 Hz, 1 H), 7.74–
7.71 (m, 2 H), 7.51–7.45 (m, 3 H), 5.99–5.88 (m, 1 H), 5.30–5.25
(Boc)2O (742 mg, 3.40 mmol) afforded the crude product, which (m, 2 H), 5.14–5.10 (m, 1 H), 4.89–4.80 (m, 1 H), 4.48 (dd, J = 5.5,
was purified by flash column chromatography (hexane/EtOAc, 9:1)
14.9 Hz, 1 H), 4.10–4.04 (m, 3 H), 1.43 (s, 9 H) ppm. 13C NMR
to give 4h (464 mg, 1.75 mmol, 93%) as a yellow oil. IR (NaCl):
(75 MHz, CDCl3): δ = 152.4, 148.6, 145.5, 143.9, 140.0, 131.9,
Eur. J. Org. Chem. 2015, 4214–4223
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4219

A. M. Cuadro, J. J. Vaquero et al.
FULL PAPER
130.6, 129.7, 128.4, 127.5, 121.5, 120.5 (q, J = 318.4 Hz), 85.1, 57.6,
C16H21F3N2O5S (410.42): calcd. C 46.83, H 5.16, N 6.83, S 7.81;
53.0, 41.8, 27.8 ppm. MS (ESI+): m/z (%) = 317 (12), 373 (100) found C 46.54, H 5.87, N 6.72, S 7.69.
[M]+. C22H26ClN2O5SF3 (522.91): calcd. C 50.53, H 5.01, N 5.36,
2-[N-Allyl-N-tert-butoxycarbonylamino]-3-methyl-1-vinylpyridinium
Triflate (6b): By following general procedure B, 5b (12 mg,
2-(N-Allyl-N-tert-butoxycarbonylamino)-1-(2-chloroethyl)iso- 0.026 mmol) and Cs2CO3 (17 mg, 0.052 mmol) were stirred at room
S 6.13; found C 50.09, H 5.07, N 5.38, S 5.27.
quinolinium Triflate (5f): By following the general procedure, the
reaction mixture of 4f (273 mg, 0.96 mmol) was stirring at room
temperature. Purification by chromatography (CH2Cl2/MeOH,
9.5:0.5) gave 5f (357 mg, 0.72 mmol, 75 %) as a yellow oil. IR
temperature to give 6b (10 mg, 0.024 mmol, 91%) as a brown oil.
IR (NaCl): ν
= 3507, 2981, 1731, 1261, 1154, 1031, 638 cm–1.
˜
max
1H NMR (200 MHz, [D6]acetone): δ = 9.14 (d, J = 6.2 Hz, 1 H),
8.81 (d, J = 7.9 Hz, 1 H), 8.21 (dd, J = 6.2, 7.9 Hz, 1 H), 7.67 (dd,
(NaCl): νmax = 3445, 2924, 1732, 1633, 1259, 1153, 1030, 638 cm–1. J = 7.9, 14.9 Hz, 1 H), 6.29 (d, J = 14.9 Hz, 1 H), 6.17–5.96 (m, 2
˜
1H NMR (300 MHz, [D6]acetone): δ = 8.98 (d, J = 6.9 Hz, 1 H),
8.72 (d, J = 6.9 Hz, 1 H), 8.49 (d, J = 8.2 Hz, 1 H), 8.35 (t, J =
7.2 Hz, 2 H), 8.23 (d, J = 7.2 Hz, 1 H), 6.27–6.13 (m, 1 H), 5.54–
5.48 (m, 1 H), 5.28 (dd, J = 1.2, 17.0 Hz, 1 H), 5.23–5.19 (m, 2 H),
4.72–4.30 (m, 4 H), 1.23 (s, 9 H) ppm. 13C NMR (75 MHz, [D6]-
acetone): δ = 138.4, 137.0, 133.3, 132.1, 129.2, 128.7, 128.1, 126.8,
122.2, 85.0, 58.7, 54.9, 42.5, 27.8 ppm. HRMS (ESI+): calcd. for
C19H24ClN2O2 [M]+ 347.1521; found 347.1525.
H), 5.29 (dd, J = 1.3, 17.1 Hz, 1 H), 5.20 (d, J = 10.5 Hz, 1 H),
4.43–4.21 (m, 2 H), 2.57 (s, 3 H), 1.35 (s, 9 H) ppm. 13C NMR
(50 MHz, [D6]acetone): δ = 151.7, 147.6, 139.7, 136.0, 132.4, 127.9,
122.3 (q, J = 322.0 Hz), 122.2, 121.5, 120.6, 84.2, 51.7, 27.9,
17.6 ppm. MS (ESI+): m/z (%) = 276 (23) [M + 1]+, 275 (100)
[M]+. C17H23F3N2O5S (424.44): calcd. C 48.11, H 5.46, N 6.60, S
7.55; found C 47.60, H 5.73, N 6.66, S 7.41.
2-[N-Allyl-N-tert-butoxycarbonylamino]-5-phenyl-1-vinylpyridin-
ium Triflate (6e): By following general procedure B, 5e (0.828 g,
1.59 mmol) and Cs2CO3 (1.55 g, 4.77 mmol) were stirred at room
2-(N-Allyl-N-tert-butoxycarbonylamino)-1-(2-chloroethyl)-4-meth-
oxypyridinium Triflate (5h): By following the general procedure, the
reaction mixture of 4h (2.56 g, 9.67 mmol) was heated at 70 °C. temperature to give 6e (0.712 g, 1.46 mmol, 92%) as a brown oil.
Purification by chromatography (CH2Cl2/MeOH, 9.5:0.5) gave 5h IR (NaCl): ν = 2983, 1727, 1621, 1522, 1492, 1372, 1260, 1152,
(3.97 g, 8.33 mmol, 87%) as a yellow oil. IR (NaCl): ν = 3018,
˜
max
1031, 763, 638 cm–1. H NMR (300 MHz, CDCl3): δ = 8.83 (s, 1
1
˜
max
2360, 1706, 1638, 1561, 1523, 1260, 1156, 1031, 756, 639 cm–1. H H), 8.66 (d, J = 8.4 Hz, 1 H), 7.92 (d, J = 8.4 Hz, 1 H), 7.71–7.69
1
NMR (300 MHz, CDCl3): δ = 8.92 (d, J = 7.4 Hz, 1 H), 7.47 (dd, (m, 2 H), 7.50–7.46 (m, 3 H), 7.31 (dd, J = 8.3, 15.3 Hz, 1 H), 6.12
J = 2.8, 7.4 Hz, 1 H), 7.12 (d, J = 2.8 Hz, 1 H), 6.02–5.88 (m, 1
(dd, J = 2.8, 15.3 Hz, 1 H), 5.97–5.86 (m, 1 H), 5.80 (dd, J = 2.8,
H), 5.32–5.26 (m, 2 H), 4.80 (dt, J = 5.0, 14.8 Hz, 1 H), 4.64–4.54 8.3 Hz, 1 H), 5.30 (dd, J = 1.1, 13.6 Hz, 1 H), 5.26 (dd, J = 1.1,
(m, 1 H), 4.47 (dd, J = 5.0, 14.8 Hz, 1 H), 4.12 (s, 3 H), 4.04–3.97
(m, 3 H), 1.44 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
173.0, 152.3, 151.3, 147.7, 131.1, 121.1, 120.5 (q, J = 320.1 Hz),
113.7, 111.8, 84.9, 58.4, 55.4, 53.1, 41.7, 27.9 ppm. MS (ESI+): m/z
6.7 Hz, 1 H), 4.33 (br. s, 2 H), 1.42 (s, 9 H) ppm. 13C NMR
(75 MHz, CDCl3): δ = 151.6, 147.8, 146.3, 141.5, 140.0, 134.5,
132.3, 131.4, 130.5, 129.7, 127.6, 127.0, 120.5 (q, J = 318.8 Hz),
120.5, 119.7, 84.7, 52.6, 27.9 ppm. HRMS (ESI+): calcd. for
C21H25N2O2 [M]+ 337.1911; found 337.1906.
( % ) = 2 7 1 ( 1 9 ) , 3 2 9 ( 3 1 ) [ M + 2 ] + , 3 2 7 ( 1 0 0 ) [ M ] +
.
C17H24ClN2O6SF3 (476.84): calcd. C 42.81, H 5.07, N 5.87, S 6.72;
found C 42.66, H 5.00, N 6.08, S 6.65.
1-[N-Allyl-N-tert-butoxycarbonylamino]-2-vinylisoquinolinium Tri-
flate (6f): By following general procedure A, 5f (12 mg,
0.024 mmol) was used to give 6f (8 mg, 0.017 mmol, 72%) as a
General Procedure A for the Synthesis of Azinium Azadienes 6: A
solution of NaOH (10 n, 0.275 mmol) was added dropwise over
10 min to a solution of the corresponding azinium salt 5 (0.05 m,
0.25 mmol) in EtOH/MeOH (3:1, 5 mL) at –10 °C or room tem-
perature. The reaction mixture was stirred for 35 min and then fil-
tered. The filtrate was evaporated at 20 °C under reduced pressure,
and the residue was purified by flash chromatography on silica gel
(CH2Cl2/MeOH, 9:1) to afford the pure azinium diene 6.
brown oil. IR (NaCl): ν
= 3543, 2982, 1732, 1446, 1276, 1033,
˜
max
639 cm–1 1H NMR (300 MHz, [D6]acetone): δ = 9.02 (d, J =
.
6.9 Hz, 1 H), 8.74 (d, J = 6.9 Hz, 1 H), 8.53–8.47 (m, 2 H), 8.40–
8.35 (m, 1 H), 8.24–8.22 (m, 1 H), 7.87 (dd, J = 8.2, 14.5 Hz, 1 H),
6.41 (d, J = 14.5 Hz, 1 H), 6.16–6.10 (m, 2 H), 5.24 (d, J = 17.1 Hz,
1 H), 5.18 (d, J = 11.2 Hz, 1 H), 4.64–4.47 (m, 2 H), 1.24 (s, 9
H) ppm. 13C NMR (75 MHz, [D6]acetone): δ = 142.3, 141.7, 138.6,
135.7, 134.8, 133.4, 132.2, 129.2, 128.7, 127.4, 127.1, 122.3 (q, J =
321.9 Hz), 121.9, 120.5, 84.6, 53.0, 27.8 ppm. HRMS (ESI+): calcd.
for C19H23N2O2 [M]+ 311.1760; found 311.1757.
General Procedure B for the Synthesis of Azinium Azadienes 6:
Cs2CO3 (2 or 3 equiv.) was added to a solution of the correspond-
ing azinium salt 5 (0.05 m, 0.25 mmol) in CH3CN/iPrOH (11:1,
5 mL), and the mixture was stirred at room temperature or 0 °C
for 2 h. The solid was removed by filtration, and the filtrate was
neutralized by the addition of acetic acid. The resulting mixture
was concentrated under reduced pressure at 20 °C to give a residue,
which was subjected to silica gel flash chromatography (CH2Cl2/
MeOH, 9.5:0.5) to afford pure azinium diene 6.
2-[N-Allyl-N-tert-butoxycarbonylamino]-4-methoxy-1-vinylpirid-
inium Triflate (6h): By following general procedure B, 5h (624 mg,
1.31 mmol) and Cs2CO3 (853 mg, 2.62 mmol) were stirred at 0 °C
to give 6h (507 mg, 1.15 mmol, 88%) as a green oil. IR (NaCl):
ν
= 3017, 1704, 1634, 1557, 1515, 1259, 1147, 1033, 946, 847,
˜
max
755, 639 cm–1 1H NMR (300 MHz, CDCl3): δ = 8.82 (d, J =
.
7.0 Hz, 1 H), 7.60 (dd, J = 2.5, 7.0 Hz, 1 H), 7.15 (d, J = 2.5 Hz,
1 H), 7.07 (dd, J = 8.3, 15.1 Hz, 1 H), 5.99 (dd, J = 2.8, 15.1 Hz,
1 H), 5.95–5.82 (m, 1 H), 5.69 (dd, J = 2.8, 8.3 Hz, 1 H), 5.28 (d,
J = 15.9 Hz, 1 H), 5.27 (d, J = 10.9 Hz, 1 H), 4.28 (br. s, 2 H), 4.16
(s, 3 H), 1.40 (s, 9 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 173.8,
151.6, 149.9, 145.4, 132.8, 131.3, 120.8, 120.6 (q, J = 320.1 Hz),
117.6, 112.7, 112.2, 84.6, 58.7, 52.7, 27.9 ppm. HRMS (ESI+):
calcd. for C16H23N2O3 [M]+ 291.1698; found 291.1703.
2-[N-Allyl-N-tert-butoxycarbonylamino]-1-vinylpyridinium Triflate
(6a): By following general procedure A, 5a (11 mg, 0.025 mmol)
was used to give 6a (7 mg, 0.017 mmol, 68%) as a brown oil. IR
(NaCl): ν
= 3565, 2983, 1747, 1567, 1129, 1033, 638 cm–1. 1H
˜
max
NMR (200 MHz, CD3OD): δ = 9.13 (d, J = 5.7 Hz, 1 H), 8.76 (td,
J = 1.6, 7.9 Hz, 1 H), 8.17–8.10 (m, 2 H), 7.55 (dd, J = 8.3, 15.2 Hz,
1 H), 6.19 (dd, J = 2.9, 15.2 Hz, 1 H), 6.11–5.94 (m, 2 H), 5.36–
5.27 (m, 2 H), 4.40 (d, J = 5.7 Hz, 2 H), 1.46 (s, 9 H) ppm. 13C
NMR (50 MHz, CD3OD): δ = 152.7, 150.3, 145.2, 135.7, 132.9,
128.7, 127.8, 122.0 (q, J = 320.0 Hz), 121.7, 119.7, 85.6, 53.5,
28.1 ppm. MS (ESI+): m/z (%) = 261 (60) [M]+, 205 (100).
General Procedure A for the Ring-Closing Metathesis of Dienes 6:
The ruthenium catalyst G-II (8.5 mg, 0.01 mmol, 5 mol-%) in dry
CH2Cl2 (1.5 mL) was added to a solution of the corresponding
4220
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Eur. J. Org. Chem. 2015, 4214–4223

Azonia Aromatic Cations by Ring-Closing Metathesis
diene 6 (0.2 mmol) in dry CH2Cl2 (1.5 mL) under argon. The reac-
tion mixture was stirred at room temperature or heated at 40 °C
for the appropriate time. The solvent was evaporated under reduced
pressure, and the residue was purified by silica gel column flash
chromatography (CH2Cl2/MeOH, 9.5:0.5).
130.2, 130.0, 128.7, 126.0, 125.4, 123.5, 122.2 (q, J = 322.5 Hz),
86.3, 41.6, 27.6 ppm. HRMS (ESI+): calcd. for C17H19N2O2 [M]+
283.1447; found 283.1437.
1,2-Dihydropyrimido[2,1-a]isoquinolinium Triflate (8f): By following
general procedure B and using Cl2CHCHCl2 as the solvent, 6f
(69 mg, 0.15 mmol) was heated at 130 °C for 4 h to give 8f (30 mg,
General Procedure B for the Ring-Closing Metathesis of Dienes 6:
The ruthenium catalyst H–G (6.2 mg, 0.01 mmol, 5 mol-%) in dry
CH2Cl2 or Cl2CHCHCl2 (1.5 mL) was added to a solution of the
corresponding diene 6 (0.15 mmol) in dry CH2Cl2 or Cl2CHCHCl2
(1.5 mL) under argon. The reaction mixture was stirred and heated
at either 80 or 130 °C for the appropriate time. The solvent was
evaporated under reduced pressure, and the residue was purified by
silica gel column flash chromatography (CH2Cl2/MeOH, 9:1).
0.090 mmol, 61%) as a brown powder; m.p. 158–159 °C. IR (KBr):
1
ν
˜
= 3272, 2923, 1694, 1652, 1593, 1281, 1030, 638 cm–1. H
max
NMR (300 MHz, [D6]acetone): δ = 9.38 (br. s, 1 H), 8.44 (d, J =
8.6 Hz, 1 H), 8.02–7.92 (m, 2 H), 7.83–7.77 (m, 1 H), 7.66 (d, J =
7.2 Hz, 1 H), 7.24 (d, J = 6.9 Hz, 1 H), 7.07 (dt, J = 2.0, 8.2 Hz, 1
H), 5.92 (dt, J = 3.3, 8.2 Hz, 1 H), 4.65 (dd, J = 2.0, 3.3 Hz, 2
H) ppm. 13C NMR (75 MHz, [D6]acetone): δ = 151.6, 136.9, 136.0,
130.8, 130.1, 128.9, 127.9, 125.3, 118.9, 113.2, 112.8, 41.4 ppm.
HRMS (ESI+): calcd. for C12H11N2 [M]+ 183.0922; found
183.0922.
1-tert-Butoxycarbonyl-1,2-dihydropyrido[1,2-a]pyrimidin-5-ium
Triflate (7a): By following general procedure A, 6a (82 mg,
0.20 mmol) was stirred at 40 °C for 4 h to give 7a (46 mg,
0.12 mmol, 60%) as a gray powder; m.p. 136–138 °C. IR (KBr):
1-tert-Butoxycarbonyl-8-methoxy-1,2-dihydropyrido[1,2-a]pyr-
imidin-5-ium Triflate (7h): By following general procedure A, 6h
(357 mg, 0.81 mmol) was stirred at 40 °C for 24 h to give 7h
(285 mg, 0.69 mmol, 86%) as a gray powder; m.p. 113–115 °C. IR
ν
˜
= 3089, 1726, 1501, 1257, 1153, 1035, 644 cm–1. 1H NMR
max
(500 MHz, CD3OD): δ = 8.52 (dd, J = 1.7, 6.5 Hz, 1 H), 8.40–8.36
(m, 1 H), 8.34–8.33 (m, 1 H), 7.65–7.62 (m, 1 H), 7.36 (dt, J = 2.1,
7.6 Hz, 1 H), 6.44 (dt, J = 4.4, 7.6 Hz, 1 H), 4.66 (dd, J = 2.1,
4.4 Hz, 2 H), 1.63 (s, 9 H) ppm. 13C NMR (50 MHz, CD3OD): δ
= 146.5, 140.7, 129.0, 123.5, 123.4, 121.8, 87.4, 42.7, 28.0 ppm. MS
(ESI+): m/z (%) = 177 (88), 233 (100) [M]+. C14H17F3N2O5S
(382.36): calcd. C 43.98, H 4.48, N 7.33, S 8.39; found C 43.95, H
4.53, N 7.31, S 8.36.
(KBr): νmax = 3095, 2924, 1723, 1645, 1550, 1506, 1339, 1258, 1142,
˜
1
1030, 875, 763, 637 cm–1. H NMR (300 MHz, CD3OD): δ = 8.36
(d, J = 7.5 Hz, 1 H), 7.82 (d, J = 2.8 Hz, 1 H), 7.25–7.20 (m, 2 H),
6.26 (dt, J = 4.4, 7.5 Hz, 1 H), 4.59 (dd, J = 2.2, 4.4 Hz, 2 H), 4.16
(s, 3 H), 1.63 (s, 9 H) ppm. 13C NMR (75 MHz, CD3OD): δ =
173.0, 151.9, 149.7, 142.2, 128.1, 121.8 (q, J = 318.1 Hz), 119.9,
110.4, 106.3, 87.1, 58.5, 42.5, 28.1 ppm. MS (ESI+): m/z (%) = 207
(18), 263 (100) [M]+. C15H19F3N2O6S (412.38): calcd. C 43.69, H
4.64, N 6.79, S 7.78; found C 44.32, H 5.19, N 5.81, S 7.30.
1-tert-Butoxycarbonyl-9-methyl-1,2-dihydropyrido[1,2-a]pyrimidin-
5-ium Triflate (7b): By following general procedure A, 6b (85 mg,
0.20 mmol) was stirred at room temperature for 3 h to give 7b
(77 mg, 0.19 mmol, 97%) as a brown powder; m.p. 147–149 °C. IR
General Procedure for the Synthesis of Dihydroazaquinolizinium
Salts 8: A solution of the corresponding N-protected azaquinolizin-
ium salt 7 (0.1 mmol) in a mixture of 50% TFA/CH2Cl2 (10 mL)
was stirred at room temperature for the appropriate time. The sol-
vent was evaporated under reduced pressure, and the residue was
purified by silica gel column flash chromatography (CH2Cl2/
MeOH, 9.5:0.5) to give the pure 1-azaquinolizinium salt 8.
(KBr): νmax = 3316, 3093, 2925, 1737, 1494, 1329, 1257, 1156, 1030,
˜
638 cm–1 1H NMR (200 MHz, [D6]acetone): δ = 8.84 (d, J =
.
6.3 Hz, 1 H), 8.55 (d, J = 7.9 Hz, 1 H), 8.01–7.94 (m, 1 H), 7.71
(d, J = 7.6 Hz, 1 H), 6.77 (dt, J = 4.3, 7.6 Hz, 1 H), 4.68 (br. s, 2 H),
2.49 (s, 3 H), 1.52 (s, 9 H) ppm. 13C NMR (50 MHz, [D6]acetone): δ
= 150.9, 149.0, 139.6, 137.0, 130.1, 127.7, 124.7, 122.1 (q, J =
320.3 Hz), 85.7, 41.6, 27.8, 18.4 ppm. MS (ESI+): m/z (%) = 191
(87), 247 (100) [M]+. C15H19F3N2O5S (396.39): calcd. C 45.45, H
4.83, N 7.07, S 8.09; found C 45.50, H 4.88, N 7.19, S 8.03.
1,2-Dihydropyrido[1,2-a]pyrimidin-5-ium Triflate (8a): By following
the general procedure, the reaction of 7a (38 mg, 0.10 mmol) was
stirred for 2 h to give 8a (21 mg, 0.074 mmol, 74%) as a brown
1-tert-Butoxycarbonyl-7-phenyl-1,2-dihydropyrido[1,2-a]pyrimidin-5-
ium Triflate (7e): By following general procedure A, 6e (242 mg,
0.50 mmol) was stirred at 40 °C for 24 h to give 7e (156 mg,
0.34 mmol, 68%) as a brown powder; m.p. 122–124 °C. IR (KBr):
powder; m.p. 73–75 °C. IR (KBr): ν
= 3499, 2923, 1690, 1659,
˜
max
1577, 1254, 1031, 639 cm–1. 1H NMR (500 MHz, CD3OD): δ =
7.76–7.73 (m, 1 H), 7.72 (d, J = 6.6 Hz, 1 H), 6.87 (d, J = 8.3 Hz,
1 H), 6.85 (d, J = 9.2 Hz, 1 H), 6.80 (at, J = 6.8 Hz, 1 H), 5.82 (dt,
J = 3.7, 8.3 Hz, 1 H), 4.42–4.41 (m, 2 H) ppm. 13C NMR (75 MHz,
CD3OD): δ = 152.7, 144.2, 137.3, 127.4, 121.8 (q, J = 318.2 Hz),
115.8, 115.3, 113.9, 40.6 ppm. HRMS (ESI+): calcd. for C8H9N2
[M]+ 133.0766; found 133.0764.
ν
= 3019, 1735, 1528, 1373, 1260, 1216, 1157, 1031, 757,
˜
max
638 cm–1. H NMR (300 MHz, CD3OD): δ = 8.90 (d, J = 2.2 Hz,
1 H), 8.69 (dd, J = 2.2, 9.3 Hz, 1 H), 8.40 (d, J = 9.3 Hz, 1 H),
7.81 (dd, J = 1.4, 8.0 Hz, 2 H), 7.64–7.54 (m, 3 H), 7.44 (d, J =
7.7 Hz, 1 H), 6.48 (dt, J = 4.4, 7.7 Hz, 1 H), 4.69 (dd, J = 1.9,
4.4 Hz, 2 H), 1.66 (s, 9 H) ppm. 13C NMR (75 MHz, CD3OD): δ
= 151.7, 147.4, 144.5, 138.2, 135.3, 134.4, 131.0, 130.7, 129.2, 128.0,
123.5, 123.4, 121.8 (q, J = 318.6 Hz), 87.4, 42.9, 28.0 ppm. HRMS
(ESI+): calcd. for C19H21N2O2 [M]+ 309.1598; found 309.1585.
1
9-Methyl-1,2-dihydropyrido[1,2-a]pyrimidin-5-ium Triflate (8b): By
following the general procedure, the reaction of 7b (40 mg,
0.10 mmol) was stirred for 1 h to give 8b (28 mg, 0.095 mmol, 95%)
as a greenish oil. IR (NaCl): ν
= 3314, 2923, 1694, 1651, 1573,
˜
max
1258, 1031, 666 cm–1. H NMR (200 MHz, CD3OD): δ = 7.65 (d,
J = 7.0 Hz, 2 H), 6.89 (dt, J = 2.2, 8.3 Hz, 1 H), 6.77 (t, J = 7.0 Hz,
1 H), 5.85 (dt, J = 3.2, 8.3 Hz, 1 H), 4.46 (dd, J = 2.2, 3.2 Hz, 2
H), 2.21 (s, 3 H) ppm. 13C NMR (75 MHz, CD3OD): δ = 143.2,
135.2, 127.7, 124.6, 123.9, 115.6, 113.5, 41.2, 16.3 ppm. MS (ESI+):
m/z (%) = 147 (100) [M]+. C10H11F3N2O3S (296.27): calcd. C 40.54,
H 3.74, N 9.46, S 10.82; found C 40.89, H 3.53, N 9.33, S 10.75.
1
1-tert-Butoxycarbonyl-1,2-dihydropyridopyrimido[2,1-a]isoquinol-
inium Triflate (7f): By following general procedure B and using
CH2Cl2 as solvent, after heating at 40 °C for 5 h, to give 7f (16 mg,
0.038 mmol, 25%) as a greenish oil. IR (NaCl): ν
= 3564, 3093,
˜
max
2924, 1652, 1455, 1249, 1030, 638 cm–1 1H NMR (300 MHz,
.
[D6]acetone): δ = 8.65 (d, J = 6.9 Hz, 1 H), 8.41 (d, J = 8.2 Hz, 1
H), 8.39 (d, J = 6.9 Hz, 1 H), 8.34 (d, J = 7.9 Hz, 1 H), 8.27–8.22
(m, 1 H), 8.13–8.08 (m, 1 H), 7.78 (d, J = 7.2 Hz, 1 H), 6.79 (dt, J
7-Phenyl-1,2-dihydropyrido[1,2-a]pyrimidin-5-ium Triflate (8e): By
= 4.6, 7.2 Hz, 1 H), 4.88 (br. s, 2 H), 1.33 (s, 9 H) ppm. 13C NMR following the general procedure, the reaction of 7e (156 mg,
(75 MHz, [D6]acetone): δ = 151.5, 149.4, 139.5, 137.5, 132.3, 131.4, 0.34 mmol) was stirred for 4 h to give 8e (112 mg, 0.31 mmol, 92%)
Eur. J. Org. Chem. 2015, 4214–4223
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4221

A. M. Cuadro, J. J. Vaquero et al.
FULL PAPER
as a green powder; m.p. 158–160 °C. IR (KBr): ν
= 3234, 1694,
(dd, J = 1.9, 9.1 Hz, 1 H), 8.74 (d, J = 9.1 Hz, 1 H), 8.37 (dd, J =
˜
max
1663, 1587, 1259, 1155, 1030, 763, 635 cm–1. H NMR (300 MHz, 4.2, 6.8 Hz, 1 H), 8.03 (dd, J = 1.3, 8.1 Hz, 2 H), 7.71–7.64 (m, 3
1
CD3OD): δ = 8.13–8.08 (m, 2 H), 7.65–7.61 (m, 2 H), 7.55–7.43
(m, 3 H), 6.98 (dt, J = 2.2, 8.1 Hz, 1 H), 6.96 (d, J = 9.0 Hz, 1 H), 145.1, 142.0, 138.1, 135.4, 134.2, 131.4, 130.7, 128.9, 128.7, 122.2
5.88 (dt, J = 3.4, 8.1 Hz, 1 H), 4.46 (dd, J = 2.2, 3.4 Hz, 2 H) ppm.
(q, J = 321.5 Hz), 120.8 ppm. 19F NMR (282 MHz, CD3OD): δ =
13C NMR (75 MHz, CD3OD): δ = 151.5, 143.3, 135.3, 134.2, 130.4, –80.2 ppm. HRMS (ESI+): calcd. for C14H11N2 [M]+ 207.0917;
H) ppm. 13C NMR (125 MHz, [D6]acetone): δ = 161.7, 150.9,
129.8, 127.7, 127.6, 127.1, 121.8 (q, J = 317.9 Hz), 115.9, 115.5,
40.8 ppm. MS (ESI+): m/z (%) = 209 (100) [M]+. C15H13F3N2O3S
(358.34): calcd. C 50.28, H 3.66, N 7.82, S 8.95; found C 50.37, H
4.28, N 7.79, S 9.25.
found 207.0919.
Pyrimido[2,1-a]isoquinolinium Triflate (1f): By following the general
procedure, 8f (25 mg, 0.075 mmol) and 10% Pd/C (10 mg, 40%)
were heated at 200 °C for 4 h to give 1f (19 mg, 0.058 mmol, 77%)
as a brown oil. IR (NaCl): ν
= 3584, 3099, 2925, 1651, 1621,
˜
8-Methoxy-1,2-dihydropyrido[1,2-a]pyrimidin-5-ium Triflate (8h):
By following the general procedure, the reaction of 7h (216 mg,
0.52 mmol) was stirred for 4 h to give 8h (157 mg, 0.50 mmol, 97%)
max
1455, 1256, 1162, 1029, 672 cm–1. 1H NMR (500 MHz, [D6]acet-
one): δ = 9.96 (dd, J = 1.6, 6.7 Hz, 1 H), 9.83 (dd, J = 1.6, 4.4 Hz,
1 H), 9.42 (d, J = 8.2 Hz, 1 H), 9.11 (d, J = 7.2 Hz, 1 H), 8.57 (d,
J = 7.1 Hz, 1 H), 8.49 (dd, J = 4.4, 6.7 Hz, 1 H), 8.42 (d, J =
8.2 Hz, 1 H), 8.36–8.29 (m, 1 H), 8.25–8.19 (m, 1 H) ppm. 13C
NMR (125 MHz, [D6]acetone): δ = 163.0, 147.4, 136.7, 135.5,
132.3, 131.3, 128.9, 128.2, 126.6, 125.1, 122.2 (q, J = 321.6 Hz),
121.2 ppm. 19F NMR (282 MHz, CD3OD): δ = –80.2 ppm. HRMS
(ESI+): calcd. for C12H9N2 [M]+ 181.0766; found 181.0766.
as a gray powder; m.p. 193–195 °C. IR (KBr): ν
= 3235, 1671,
˜
max
1663, 1583, 1494, 1251, 1034, 831, 802, 640 cm–1 1H NMR
.
(500 MHz, CD3OD): δ = 7.61 (d, J = 7.5 Hz, 1 H), 6.78 (dt, J =
2.2, 8.2 Hz, 1 H), 6.44 (dd, J = 2.6, 7.5 Hz, 1 H), 6.22 (d, J =
2.6 Hz, 1 H), 5.70 (dt, J = 3.4, 8.2 Hz, 1 H), 4.28 (dd, J = 2.2,
3.4 Hz, 2 H), 3.94 (s, 3 H) ppm. 13C NMR (125 MHz, CD3OD): δ
= 171.1, 154.0, 138.7, 126.7, 121.7 (q, J = 318.3 Hz), 113.6, 106.9,
93.4, 57.6, 40.2 ppm. MS (ESI+): m/z (%) = 163 (100) [M]+.
C10H11F3N2O4S (312.27): calcd. C 38.46, H 3.55, N 8.97, S 10.27;
found C 38.76, H 3.18, N 9.31, S 10.92.
8-Methoxypyrido[1,2-a]pyrimidin-5-ium Triflate (1h): By following
the general procedure, 8h (41 mg, 0.13 mmol) and 30 % Pd/C
(17 mg) were heated at 140 °C for 6 h to give 1h (38 mg, 0.12 mmol,
94%) as a brown powder; m.p. 146–148 °C. IR (KBr): νmax = 3494,
˜
General Procedure for the Synthesis of Azaquinolizinium Salts 1: A
mixture of 8 and Pd/C (10 or 30%) was heated at 140 or 200 °C
for the appropriate time. The reaction mixture was cooled to room
temperature, suspended in acetone, and filtered through Celite. The
solvent was removed under reduced pressure. The azaquinolizinium
salt was precipitated by the addition of acetone/Et2O at 0 °C, fil-
tered, and washed with Et2O to give the pure 1-azaquinolizinium
salt 1.
3098, 1654, 1372, 1259, 1170, 1149, 1036, 640 cm–1 1H NMR
.
(500 MHz, [D6]acetone): δ = 9.54 (dd, J = 1.5, 6.9 Hz, 1 H), 9.43
(dd, J = 1.5, 4.2 Hz, 1 H), 9.27 (d, J = 7.5 Hz, 1 H), 7.98 (dd, J =
4.2, 6.9 Hz, 1 H), 7.96 (d, J = 2.9 Hz, 1 H), 7.89 (dd, J = 2.9,
7.5 Hz, 1 H), 4.33 (s, 3 H) ppm. 13C NMR (125 MHz, [D6]acetone):
δ = 169.9, 162.2, 152.3, 144.4, 139.4, 122.2 (q, J = 321.4 Hz), 117.7,
117.5, 107.4, 58.8 ppm. 19F NMR (282 MHz, CD3OD): δ =
–80.2 ppm. HRMS (ESI+): calcd. for C9H9N2O [M]+ 161.0709;
found 161.0707.
Pyrido[1,2-a]pyrimidin-5-ium Triflate (1a): By following the general
procedure, 8a (25 mg, 0.089 mmol) and 10% Pd/C (10 mg) were
heating at 200 °C for 2 h to give 1a (18 mg, 0.065 mmol, 73%) as
2-(N-Allylamino)-4-methoxypyridine (9): In a 2 dram vial equipped
with a magnetic stir bar were combined allylamine (77 mg, 101 μL,
1.32 mmol), iPr2EtN (509 mg, 690 μL, 3.94 mmol), and dichloro-
methane (3 mL). 4-Methoxypyridine N-oxide (131 mg, 1.05 mmol)
was added to the solution followed by PyBroP (672 mg,
1.37 mmol). The reaction was capped and stirred at room tempera-
ture overnight. Upon completion (TLC analysis), the reaction was
poured into saturated sodium hydrogen carbonate (15 mL), and the
resulting mixture was extracted with dichloromethane (DCM, 3ϫ
15 mL). The combined organic layers were washed with brine, dried
with Na2SO4, and concentrated under vacuum. The crude material
was purified by flash column chromatography on silica gel (hexane/
EtOAc, 4:6) to afford 9 as a yellow oil (126 mg, 0.77 mmol, 73%).
a brown powder; m.p. 156–158 °C. IR (KBr): ν
= 3115, 3088,
˜
max
1637, 1369, 1268, 1155, 1029, 823, 636 cm–1. H NMR (300 MHz,
[D6]DMSO): δ = 9.66 (d, J = 6.9 Hz, 1 H), 9.53 (d, J = 4.4 Hz, 1
H), 9.31 (d, J = 6.9 Hz, 1 H), 8.70–8.64 (m, 1 H), 8.56 (d, J =
8.7 Hz, 1 H), 8.24–8.18 (m, 2 H) ppm. 13C NMR (75 MHz,
[D6]DMSO): δ = 160.5, 147.9, 143.8, 141.6, 136.9, 127.0, 123.6,
120.2 (q, J = 322.1 Hz), 118.6 ppm. 19F NMR (282 MHz,
CD3OD): δ = –80.2 ppm. HRMS (ESI+): calcd. for C8H7N2 [M]+
131.0604; found 131.0557.
1
9-Methylpyrido[1,2-a]pyrimidin-5-ium Triflate (1b): By following
the general procedure, 8b (25 mg, 0.084 mmol) and 10 % Pd/C
(10 mg, 40 %) were heated at 200 °C for 3 h to give 1b (19 mg,
IR (NaCl): ν
= 3421, 3250, 3010, 2971, 1606, 1515, 1478, 1214,
˜
max
0.064 mmol, 76%) as a gray powder; m.p. 134–136 °C. IR (KBr):
1175, 1041, 757 cm–1. H NMR (300 MHz, CDCl3): δ = 7.88 (d, J
= 5.9 Hz, 1 H), 6.18 (dd, J = 2.2, 5.9 Hz, 1 H), 5.97–5.84 (m, 1 H),
5.82 (d, J = 2.2 Hz, 1 H), 5.23 (dq, J = 1.6, 17.1 Hz, 1 H), 5.12
(dq, J = 1.6, 10.3 Hz, 1 H), 4.82 (br. s, 1 H), 3.86 (br. s, 2 H), 3.75
(s, 3 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 167.2, 160.4, 148.9,
134.8, 115.9, 101.1, 90.3, 54.8, 44.7 ppm. MS (ESI+): m/z (%) =
165 (100) [M]+. C9H12N2O (164.21): calcd. C 65.83, H 7.37, N
17.06; found C 65.02, H 7.81, N 17.65.
1
1
ν
˜
= 3393, 2925, 1637, 1360, 1262, 1151, 1030, 638 cm–1. H
max
NMR (300 MHz, [D6]acetone): δ = 9.78 (dd, J = 1.5, 6.9 Hz, 1 H),
9.63 (dd, J = 1.5, 4.3 Hz, 1 H), 9.31 (d, J = 6.4 Hz, 1 H), 8.65 (d,
J = 7.6 Hz, 1 H), 8.30 (dd, J = 4.3, 6.9 Hz, 1 H), 8.21 (at, J =
7.0 Hz, 1 H), 1.27 (s, 3 H) ppm. 13C NMR (50 MHz, [D6]acetone):
δ = 161.1, 145.4, 143.6, 142.2, 136.2, 125.0, 120.2, 17.7 ppm. 19F
NMR (282 MHz, CD3OD): δ = –80.2 ppm. MS (ESI+): m/z (%) =
145 (100) [M]+. C10H9F3N2O3S (294.26): calcd. C 40.82, H 3.08, N
9.52, S 10.90; found C 40.62, H 3.28, N 9.63, S 10.73.
Supporting Information (see footnote on the first page of this arti-
cle): Characterization data for compounds 1 and 4–9.
7-Phenylpyrido[1,2-a]pyrimidin-5-ium Triflate (1e): By following the
general procedure, 8e (27 mg, 0.08 mmol) and 10% Pd/C (11 mg)
were heated at 200 °C for 2 h to give 1e (21 mg, 0.06 mmol, 79%)
Acknowledgments
as a brown powder; m.p. 138–140 °C. IR (KBr): νmax = 3083, 1639,
˜
1389, 1276, 1161, 1029, 639 cm–1. 1H NMR (500 MHz, [D6]acet-
Financial support from the Spanish Ministerio de Economía y
Competividad (MEC) (project number CTQ2011-24715), the Insti-
one): δ = 9.86–9.84 (m, 2 H), 9.64 (dd, J = 1.9, 4.2 Hz, 1 H), 9.15
4222
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© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2015, 4214–4223

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Received: March 26, 2015
Published Online: May 27, 2015
Eur. J. Org. Chem. 2015, 4214–4223
© 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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