Copper-catalyzed tandem amide n-arylation and regioselective cyclization of 2-alkynylbenzamides

Article abstract of DOI:10.1002/ejoc.201501330

A new approach to form iminoisocoumarins from readily available and stable 2-alkynylbenzamides was developed by using a tandem copper-catalyzed N-arylation and regioselective 6-endo-dig cyclization in the presence of diaryliodonium salts, a copper catalyst, and 2,6-di-tert-butylpyridine. The arylation occurred at the nitrogen atom rather than the oxygen atom of the amide group, the alkynyl carbon, or the benzene ring of the benzamide. Cyclization occurred through a preferential nucleophilic attack by the oxygen rather than the nitrogen atom of the amide group to produce iminoisocoumarin derivatives in good to moderate yields. A new approach to produce iminoisocoumarin derivatives in moderate yields was developed by using a tandem copper-catalyzed N-arylation and regioselective 6-endo-dig cyclization of 2-alkynylbenzamides in the presence of diaryliodonium salts, a copper catalyst, and 2,6-di-tert-butylpyridine.

Full text of DOI:10.1002/ejoc.201501330

DOI: 10.1002/ejoc.201501330
Full Paper
Tandem Reactions
Copper-Catalyzed Tandem Amide N-Arylation and
Regioselective Cyclization of 2-Alkynylbenzamides
Hideki Minami,[a] Takuya Sueda,[a] Noriko Okamoto,[a] Yoshihisa Miwa,[a] Minoru Ishikura,[b]
and Reiko Yanada*[a]
Abstract: A new approach to form iminoisocoumarins from oxygen atom of the amide group, the alkynyl carbon, or the
readily available and stable 2-alkynylbenzamides was devel-
oped by using a tandem copper-catalyzed N-arylation and re-
gioselective 6-endo-dig cyclization in the presence of diaryl-
iodonium salts, a copper catalyst, and 2,6-di-tert-butylpyridine.
The arylation occurred at the nitrogen atom rather than the
benzene ring of the benzamide. Cyclization occurred through a
preferential nucleophilic attack by the oxygen rather than the
nitrogen atom of the amide group to produce iminoisocouma-
rin derivatives in good to moderate yields.
Introduction
proceeds through the nucleophilic attack of either the nitrogen
or oxygen atom of the amide on the carbon-carbon triple bond.
Herein, we describe a new copper-catalyzed tandem N-arylation
and intramolecular regioselective ring-closing reaction of 2-alk-
ynylbenzamide derivatives to give iminoisocoumarins. However,
the N-arylation of benzamide with iodonium salts is rare,
possibly because of the low electron density on the amide
nitrogen atom.[14e] Furthermore, little work has been done with
regard to the synthesis of iminoisocoumarins through the cycli-
zation of 2-alkynylbenzamides with copper catalysts.[16]
The carbon-carbon triple bond is one of the most important
functional groups in organic chemistry. In the past two decades,
electrophile-promoted nucleophilic cyclizations of alkynes with
the nucleophile in close proximity to the triple bond has proven
valuable in synthetic applications for the construction of five-
and six-membered ring compounds.[1] In this regard, a metal-
catalyzed cyclization is an attractive method to construct oxy-
gen- and nitrogen-heterocycles such as isoquinolines,[2] in-
doles,[3] furans,[4] pyrroles,[5] and coumarins[6] under mild condi-
tions. On the other hand, a variety of cross-coupling reactions
that use diaryliodonium salts have recently emerged.[7] Because
of the electron-deficient character and hyperleaving ability of
aryliodonio groups,[8] they can act as versatile arylating rea-
gents for many nucleophiles. For example, the α-arylations of
carbonyl compounds[9] and the arylations of arenes,[10] alk-
ynes,[11] alkenes,[12] oxygen nucleophiles,[13] and nitrogen nu-
cleophiles[14] have been reported.
As part of our continued interest in the synthesis of biologi-
cally interesting heterocyclic compounds, we focused on easily
accessible and stable but less reactive 2-alkynylbenzamides
1.[15] Compound 1 may be thought of having four reactive sites
for a copper-catalyzed reaction with diaryliodonium salts, that
is, arylation at a carbon atom of the aromatic ring, carboaryl-
ation of the carbon-carbon triple bond, and arylation at the
nitrogen or oxygen atom of the amide group (Scheme 1). In
addition, a transition-metal-catalyzed ring closure could occur
through either a 6-endo-dig or 5-exo-dig cyclization process that
Scheme 1. Product divergency.
Results and Discussion
[a] Faculty of Pharmaceutical Sciences, Hiroshima International University,
5-1-1 Hirokoshingai, Kure, Hiroshima 737-0112, Japan
E-mail: ryanada@ps.hirokoku-u.ac.jp
http://www.hirokoku.jp/yy/
[b] School of Pharmaceutical Sciences, Health Sciences University of Hokkaido,
Ishikari-Tobetsu, Hokkaido 061-0293, Japan
First, we examined the viability of copper catalysts in this reac-
tion. The reaction of alkyne 1a with diphenyliodonium salt 2 in
the presence of various copper catalysts was performed in
CDCl3 under nitrogen at 40 °C to give either no product or
iminoisocoumarin 3a in moderate yields (Table 1, Entries 1–5).
Under acidic conditions, 3a was accompanied by the corre-
Supporting information for this article is available on the WWW under
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sponding hydrolysis product.[17] We were delighted to find that nium salts were also employed in this reaction, in which the
the addition of the bulky 2,6-di-tert-butylpyridine (DTBP) base two aryl groups competed to mainly give N-arylated iminoiso-
in the presence of CuBr allowed the reaction to proceed coumarins 3f and 3g along with a small amount of N-mesityl-
smoothly and gave 3a in good yield (Table 1, Entry 6). Screen- eneiminoisocoumarin 3e (Table 2, Entries 6 and 7). An alkynyl-
ing the iodonium salts 2 [X = trifluoromethanesulfonate (OTf), phenyliodonium salt could not proceed in the desired reaction
BF4, and PF6] showed that diphenyliodonium triflate was the but gave a complex mixture (Table 2, Entry 8).
superior coupling partner (Table 1, Entries 6, 8, and 9). A higher
Table 2. Scope of aryl transfer reaction.
yield of the desired 3a was also obtained in DCE instead of
CDCl3 (Table 1, Entries 10 and 11). In the absence of a copper
catalyst, the synthesis of N-arylated iminoisocoumarin 3a was
unsuccessful, and the starting benzamide 1a was recovered
(Table 1, Entry 12). The yield of the product was insufficient
when 2 equiv. of DTBP, a higher reaction temperature, or other
solvents were used (Table 1, Entries 13–18). The optimization
results reveal that a copper-catalyzed N-arylation of the amide
functional group occurs along with a 6-endo-dig cyclization re-
action through a nucleophilic attack of the oxygen atom on the
carbon-carbon triple bond.
Entry Ar
Ar′
X
Product Yield [%]
1
4-MeC6H4
4-MeC6H4
4-FC6H4
OTf
OTf
PF6
OTf
Br
OTf
OTf
BF4
3b
3c
3d
3e
–
92
77
78
79
0
2
4-FC6H4
3
4
5
4-tBuC6H4
2,4,6-Me3C6H2
4-MeOC6H4
3-MeC6H4
4-CF3C6H4
-C≡ C-Bu
4-tBuC6H4
2,4,6-Me3C6H2
4-MeOC6H4
2,4,6-Me3C6H2
2,4,6-Me3C6H2
Ph
6[a]
7[a]
8
(3e) 3f (8) 80
(3e) 3g (6) 79
Table 1. Results for the optimization of the reaction conditions.[a]
–
0
[a] The reaction was performed at 30 °C.
We next turned our attention to the scope of this arylation
and cyclization reaction by using various aromatic amides with
the symmetrical diaryliodonium triflates (Table 3). Benzamides
1 that have an alkyl group for R1, which is bonded to the alkynyl
sp-hybridized carbon, underwent facile arylation of the nitro-
gen atom followed by a ring-closing reaction to give the corre-
sponding products (i.e., 3h, 3j, 3m, 3s, and 3t) in excellent
yields. On the other hand, benzamides that contain an aryl
group for R1 also produced the respective iminoisocoumarin
but in a relatively low yield. The supplementation of the reac-
tion mixture with additional diaryliodonium triflate, CuBr, and
DTBP after 20–24 h increased the yields of 3i, 3n, 3p, 3q, and
3r. An electron-withdrawing group at the 5-position of the aro-
matic ring of amide 1 had an unfavorable effect, which can be
observed in the yields of 3i, 3k, 3u, 3v, and 3w. The structures
of iminoisocoumarins 3k, 3q, and 3u were confirmed by X-ray
crystallographic analysis.[18]
Entry Catalyst
[10 mol-%]
X
Solvent
DTBP
[equiv.]
Temp.
[°C]
Yield
[%][b]
1
CuCl
OTf
OTf
OTf
OTf
OTf
OTf
OTf
BF4
PF6
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
OTf
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
CDCl3
DCE
DCE
DCE
DCE
DCE
toluene
THF[e]
AcOEt
none
none
none
none
none
1.1
1.1
1.1
1.1
1.1
1.1
1.1
2.2
1.1
1.1
1.1
1.1
1.1
40
40
40
40
40
40
40
40
40
40
40
40
40
60
80
40
40
40
(48)[c]
(48)[c]
(trace)[c]
0
2
CuBr
3
CuI
4
5
6
Cu(OAc)2
Cu(OTf)2
CuBr
(47)[c]
(85)[c]
(80)[c]
(80)[c]
(47)[c]
80
7
8
Cu(OTf)2
CuBr
9
CuBr
10
11
12
13
14
15
16
17
18
CuBr
CuBr
none
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
80
0[d]
75
56
36
70
15
40
For a comparison, copper-catalyzed arylation reactions with
organobismuth reagents were also developed.[19] As shown in
Table 3, amide 1q gave iminoisocoumarin 3q in 47 % yield. We
then tried the same reaction by using bismuthonium reagents
in the presence of 10 mol-% CuBr in DCE (Table 4). When tetra-
phenylbismuthonium tetrafluoroborate was used, 3q was ob-
tained in moderate yields with or without the addition of DTBP
at 80 °C (Table 4, Entries 1 and 2). Triphenylbismuthonium di-
fluoride also gave 3q but in a lower yield (Table 4, Entry 3).
Taking these observations into consideration, we tentatively
[a] Reactions were performed with 1a (0.2 mmol) and 2 (0.22 mmol) at a
concentration of 0.1
M. [b] Yield of isolated product is reported. [c] Deter-
mined by 1H NMR spectroscopic analysis using 1,3,5-trimethoxybenzene as
the internal standard. [d] Starting material 1a was recovered in quantitative
yield. [e] THF = tetrahydrofuran.
Having established the reaction conditions, we examined the
transfer of the aryl group from a range of diaryliodonium salts
(Table 2). We were pleased to find that some symmetrical diaryl-
iodonium salts that have aryl groups with electron-donating or proposed a reaction mechanism that includes the formation of
-withdrawing substituents were compatible in the aryl transfer the two discrete intermediates 4 and 5 (Scheme 2). In some
reaction and gave the product in good yields (Table 2, instances, compound 5 was able to be isolated from the optimi-
Entries 1–4). Although the reason is unclear, the electron-rich zation experiments. Intermediate 4 can break down to give N-
bis(4-methoxyphenyl)iodonium bromide posed
a problem arylbenzamide 5 by reductive elimination of CuBr (Scheme 2,
(Table 2, Entry 5).[10a,11c,14a] Unsymmetrical aryl(mesityl)iodo- path A). Another route involves the copper-catalyzed heterocy-
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Table 3. Scope of aromatic amide in tandem iminoisocoumarin synthesis.
Table 4. Synthesis of iminoisocoumarin 3q by using bismuthonium rea-
gents.[a]
Entry
Bismuthonium reagent
DTBP [equiv.]
Yield [%]
1
2
3
Ph4BiBF4
Ph4BiBF4
Ph3BiF2
1.1
0
1.1
65
54
41
[a] Reactions were performed with 1q (0.2 mmol), the bismuthonium reagent
(0.22 mmol), and CuBr (10 mol-%) at a 0.1
for 24 h.
M concentration in DCE at 80 °C
To obtain further insight into the mechanisms, some com-
parative studies were performed with amide 1a and 5
(Table 5).[20] When CuBr or CuBr2 was used as the catalyst, N-
phenylamide 5 was recovered (Table 5, Entries 1–3).[21] Product
3a was obtained in low yield under acidic conditions (Table 5,
Table 5. Comparative experiments.
Entry
1a
5
Catalyst
TfOH
2
DTBP
Yield
[%][a]
[equiv.] [equiv.] [10 mol-%] [equiv.] [equiv.] [equiv.]
1
0
0
0
0
0
0
0
0.5
1
1
1
1
1
1
1
0.5
CuBr
CuBr
CuBr2
–
CuBr
CuBr
CuBr
CuBr
0
0
0
1.1
1.1
0
0
0
0
0
0
1.1
1.1
1.1
0
0
0
0
0
0
1.1
1.1
0
0
0
21
68
66
29
81[c]
2[b]
3
4
5
6
7
[a] Additional 2 (0.22 mmol), CuBr (0.022 mmol), and DTBP (0.22 mmol) were
added after 20–24 h. The reaction mixture was then stirred for 20–24 h at
40 °C.
0
0
8
clization of intermediate 4 through an intramolecular nucleo-
philic attack of the amide oxygen atom on the alkynyl carbon
(Scheme 2, path B).
[a] Determined by 1H NMR analysis by using 1,3,5-trimethoxybenzene as an
internal standard. [b] Reaction was conducted under oxygen. [c] Determined
by 1H NMR analysis using dichloromethane as an internal standard.
Scheme 2. Proposed reaction mechanism.
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reaction was monitored by TLC analysis to establish its completion.
Chromatography on a neutral silica gel column (hexane/ethyl ace-
tate) afforded the corresponding iminoisocoumarin 3. Iminoiso-
coumarins 3a,[20] 3p,[20] 3q,[25] and 3r[29] are known compounds.
Entry 4). The reaction of CuBr with TfOH or diphenyliodonium
salt 2 gave 3a in moderate yields (Table 5, Entries 5 and 6). The
further addition of DTBP decreased the product yield (Table 5,
Entry 7). The reaction that used 0.5 equiv. of both amide 1a
and 5 with CuBr, diphenyliodonium triflate 2, and DTBP pro-
ceeded well to give 3a in 81 % yield (Table 5, Entry 8). These
results imply that not only N-phenylamide 5 but also in situ
generated 4 could be reactive intermediates in paths A and B
to produce iminoisocoumarin 3.
N-Phenylbenzamide Derivative 5: Known compound, see ref.[26]
4-Fluoro-2-(hex-1-ynyl)benzamide (1h): Pale yellow solid
1
(179 mg, 82 % yield); m.p. 83–84 °C. H NMR (600 MHz, CDCl3): δ =
8.15 (dd, J = 8.2, 6.2 Hz, 1 H), 7.65 (br. s, 1 H), 7.17 (dd, J = 8.9,
2.1 Hz, 1 H), 7.09 (ddd, J = 8.9, 8.2, 2.1 Hz, 1 H), 6.35 (br. s, 1 H),
2.50 (t, J = 7.2 Hz, 2 H), 1.66–1.60 (m, 2 H), 1.52–1.46 (m, 2 H), 0.96
(dd, J = 7.6, 6.2 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 167.2,
163.7 (d, JC,F = 252.9 Hz), 133.0 (d, JC,F = 8.7 Hz), 130.3 (d, JC,F
2.9 Hz), 123.3 (d, JC,F = 10.1 Hz), 120.2 (d, JC,F = 23.1 Hz), 115.7 (d,
C,F = 21.7 Hz), 99.2, 78.8 (d, JC,F = 2.9 Hz), 30.3, 22.1, 19.3, 13.6 ppm.
=
Conclusions
J
IR (CHCl ): ν = 3503, 3035, 2962, 1669, 1605, 1585, 1366, 1267, 1174,
˜
3
877, 697, 687, 684 cm–1. MS (EI): m/z = 219 [M]+. HRMS (EI): calcd.
In summary, we have developed a new approach to form imino-
isocoumarins from readily available and stable 2-alkynyl-
benzamides by using a tandem Cu-catalyzed N-arylation and
regioselective 6-endo-dig cyclization process in the presence of
diaryliodonium salts, a copper catalyst, and 2,6-di-tert-butylpyr-
idine. Arylation occurred at the nitrogen atom rather than the
oxygen atom of the amide group, the alkynyl carbon, or the
benzene ring, and cyclization occurred preferentially by nucleo-
philic attack of the oxygen rather than the nitrogen atom of
the amide group to produce the iminoisocoumarins.
for C13H14NOF 219.1059; found 219.1062.
2-Fluoro-6-(hex-1-ynyl)benzamide (1j): Pale yellow solid (195 mg,
1
89 % yield); m.p. 125–127 °C. H NMR (600 MHz, CDCl3): δ = 7.32–
7.24 (m, 2 H), 7.04 (dd, J = 8.9, 8.2 Hz, 1 H), 6.21 (br. s, 1 H), 6.00
(br. s, 1 H), 2.43 (t, J = 7.2 Hz, 2 H), 1.62–1.56 (m, 2 H), 1.50–1.43 (m,
2 H), 0.94 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ =
166.0, 159.2 (d, JC,F = 250.0 Hz), 130.8 (d, JC,F = 10.1 Hz), 128.7 (d,
JC,F = 2.9 Hz), 126.0 (d, JC,F = 17.3 Hz), 123.8 (d, JC,F = 5.8 Hz), 115.4
(d, JC,F = 23.1 Hz), 96.5, 77.2, 30.5, 22.0, 19.3, 13.6 ppm. IR (CHCl3):
ν = 3521, 3404, 3008, 2962, 2936, 1684, 1609, 1589, 1564, 1467,
˜
1458, 1368, 1283, 690 cm–1. MS (EI): m/z = 219 [M]+. HRMS (EI):
calcd. for C13H14NOF 219.1059; found 219.1053.
2-(Hex-1-ynyl)-5-methylbenzamide (1l): Pale yellow solid (32 mg,
15 % yield); m.p. 113–114 °C. 1H NMR (600 MHz, CDCl3): δ = 7.94 (s,
1 H), 7.75 (br. s, 1 H), 7.38 (d, J = 7.9 Hz, 1 H), 7.22 (d, J = 7.9 Hz, 1
H), 6.60 (br. s, 1 H), 2.48 (t, J = 7.2 Hz, 2 H), 2.38 (s, 3 H), 1.64–1.58
(m, 2 H), 1.51–1.44 (m, 2 H), 0.95 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 168.6, 138.4, 133.7, 133.7, 131.8, 130.8, 118.0,
Experimental Section
General Methods: The 1H and 13C NMR spectroscopic data were
recorded with a 600 MHz spectrometer. Chemical Shifts [δ (ppm)]
are reported by using tetramethylsilane as the internal standard,
and the NMR data are described as follows: chemical shift, multiplic-
ity [s (singlet), d (doublet), t (triplet), q (quartet), br. (broad), and m
(multiplet)], coupling constant [J (Hz)], relative integration value.
Infrared spectra were obtained with an FT spectrometer. Mass spec-
troscopy experiments were performed on a double-focusing mass
spectrometer by using EI as the ionization mode. Analytical thin
layer chromatography was performed on Merck silica gel 60 F254
TLC plates.
97.0, 79.7, 30.5, 22.1, 21.3, 19.3, 13.6 ppm. IR (CHCl ): ν = 3499, 3378,
˜
3
3037, 3007, 2961, 2934, 2875, 2864, 1669, 1608, 1587, 1488, 1467,
1419, 1380, 1354, 1237, 828 cm–1. MS (EI): m/z = 215 [M]+. HRMS
(EI): calcd. for C14H17NO 215.1310; found 215.1311.
2-[(4-Fluorophenyl)ethynyl]benzamide (1o): Pale yellow solid
(116 mg, 97 % yield); m.p. 159–160 °C. 1H NMR (600 MHz, CDCl3):
δ = 8.10 (dd, J = 7.6, 1.4 Hz, 1 H), 7.62 (d, J = 7.6 Hz, 1 H), 7.54–7.45
(m, 4 H), 7.32 (br. s, 1 H), 7.09 (dd, J = 8.9, 8.2 Hz, 2 H), 6.06 (br. s,
General Procedure for the Synthesis of the 2-Alkynylbenz-
1 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 168.3, 163.0 (d, JC,F
=
amide: To a solution of 2-bromo- or 2-iodobenzamide (1.0 mmol, 251.5 Hz), 134.7, 133.5 (t, JC,F = 8.7 Hz), 131.1, 130.2, 128.9, 120.0,
1.00 equiv.) in Et3N (0.2
M) were added triphenylphosphine
118.2 (d, JC,F = 4.3 Hz), 116.0 (d, JC,F = 21.7 Hz), 94.6, 87.4 ppm. IR
(0.02 equiv.), CuI (0.02 equiv.), Pd(OAc)2 (0.02 equiv.), and the termi-
nal alkyne (1.5 equiv.), and the resulting mixture was stirred at 70 °C
(CHCl ): ν = 3509, 3393, 1670, 1602, 1584, 1508, 1373, 1238, 838,
3
˜
798, 756, 747, 692 cm–1. MS (EI): m/z = 239 [M]+. HRMS (EI): calcd.
under nitrogen. The progress of the reaction was monitored by TLC for C15H10NOF 239.0746; found 239.0746.
analysis to establish its completion. NH4Cl solution was then added,
2-(Cyclohexylethynyl)benzamide (1t): Pale yellow solid (208 mg,
and the mixture was extracted with chloroform (3×). The combined
organic phases were dried with anhydrous MgSO4 and concen-
trated under reduced pressure. Chromatography of the residue on
a silica gel column (hexane/ethyl acetate) afforded the correspond-
ing 2-alkynylbenzamide. 2-Alkynylbenzamides 1a,[15a] 1i,[15d]
1k,[15d] 1m,[15d] 1n,[22] 1p,[23] 1q,[15d] 1r,[24] and 1s[15d] are known
compounds.
92 % yield); m.p. 119–120 °C. 1H NMR (600 MHz, CDCl3): δ = 8.13
(dd, J = 7.6, 2.1 Hz, 1 H), 7.76 (br. s, 1 H), 7.49 (dd, J = 7.3, 1.8 Hz, 1
H), 7.43–7.37 (m, 2 H), 6.36 (br. s, 1 H), 2.66–2.67 (m, 1 H), 1.93–1.90
(m, 2 H), 1.78–1.73 (m, 2 H), 1.58–1.54 (m, 3 H), 1.39–1.36 (m, 3
H) ppm. 13C NMR (150 MHz, CDCl3): δ = 168.3, 133.9, 133.7, 130.9,
130.3, 128.1, 121.0, 101.8, 79.7, 32.3, 29.9, 25.7, 24.9 ppm. IR (CHCl3):
ν = 3499, 3377, 3007, 2936, 2857, 1669, 1585, 1448, 1370, 699, 686,
˜
670, 662 cm–1. MS (EI): m/z = 227 [M]+. HRMS (EI): calcd. for
General Procedure for the Synthesis of the Iminoisocoumarin:
To a solution of the 2-alkynylbenzamide (0.2 mmol, 1.00 equiv.) in
DCE were added the diphenyliodonium trifluoromethanesulfonate
C15H17NO 227.1310; found 227.1313.
2-(Cyclohexylethynyl)-5-nitrobenzamide (1u): Pale yellow solid
(1.1 equiv.), CuBr (0.1 equiv.), and DTBP (1.1 equiv.), and the result- (159 mg, 58 % yield); m.p. 111–112 °C. 1H NMR (600 MHz, CDCl3):
ing mixture was stirred at 40 °C under nitrogen. The progress of the
δ = 8.97 (d, J = 2.7 Hz, 1 H), 8.24 (dd, J = 8.6, 2.7 Hz, 1 H), 7.67 (br.
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s, 1 H), 7.65 (d, J = 8.6 Hz, 1 H), 6.75 (s, 1 H), 2.76–2.72 (m, 1 H),
809, 695, 688 cm–1. MS (EI): m/z = 291 [M]+. HRMS (EI): calcd. for
1.97–1.94 (m, 2 H), 1.80–1.72 (m, 2 H), 1.61–1.55 (m, 3 H), 1.44–1.35 C20H21NO 291.1623; found 291.1625.
(m, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 166.0, 146.9, 135.5,
134.9, 127.4, 125.7, 125.2, 107.6, 78.6, 32.0, 30.1, 25.6, 24.8 ppm. IR
(Z)-N-(3-Butyl-1H-isochromen-1-ylidene)-4-trifluoromethyl-
aniline (3g): Pale yellow oil (55 mg, 79 % yield). 1H NMR (600 MHz,
CDCl3): δ = 8.32 (d, J = 8.2 Hz, 1 H), 7.60–7.52 (m, 3 H), 7.39 (dd, J =
7.6, 7.6 Hz, 1 H), 7.27–7.20 (m, 3 H), 6.04 (s, 1 H), 2.34 (t, J = 7.6 Hz,
2 H), 1.53–1.49 (m, 2 H), 1.34–1.30 (m, 2 H), 0.89 (t, J = 7.2 Hz, 3
H) ppm. 13C NMR (150 MHz, CDCl3): δ = 156.3, 151.5, 150.4, 134.2,
(CHCl ): ν = 3499, 3008, 2937, 2858, 2222, 1684, 1680, 1605, 1587,
˜
3
1525, 1451, 1424, 1349, 1345, 901, 845, 810, 696 cm–1. MS (EI): m/z =
272 [M]+. HRMS (EI): calcd. for C15H16N2O3 272.1161; found
272.1169.
132.7, 127.6, 127.5, 125.8, 125.8, 125.8, 125.8, 123.7 (d, JC,F
=
(Z)-N-(3-Butyl-1H-isochromen-1-ylidene)-4-methylaniline (3b):
Pale yellow oil (53 mg, 92 % yield). H NMR (600 MHz, CDCl3): δ =
300.6 Hz), 122.7, 102.1, 32.6, 28.8, 21.9, 13.8 ppm. IR (CHCl ): ν =
1
˜
3
3035, 3010, 1673, 1604, 1324, 1235, 1159, 1123, 1066, 810,
667 cm–1. MS (EI): m/z = 345 [M]+. HRMS (EI): calcd. for C20H18NOF3
345.1340; found 345.1346.
8.32 (d, J = 8.2 Hz, 1 H), 7.47 (dd, J = 7.6, 1.4 Hz, 1 H), 7.34 (dd, J =
8.2, 7.6 Hz, 1 H), 7.17–7.12 (m, 5 H), 5.96 (s, 1 H), 2.35–2.32 (m, 5 H),
1.58–1.52 (m, 2 H), 1.37–1.32 (m, 2 H), 0.91 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (150 MHz, CDCl3): δ = 156.3, 150.1, 143.8, 134.0, 132.9,
132.1, 129.1, 127.4, 127.3, 124.5, 123.5, 122.9, 101.7, 32.7, 28.8, 22.0,
(Z)-N-(3-Butyl-6-fluoro-1H-isochromen-1-ylidene)aniline (3h):
1
Pale yellow oil (49 mg, 82 % yield). H NMR (600 MHz, CDCl3): δ =
21.0, 13.8 ppm. IR (CHCl3): ν = 3035, 3010, 1672, 810, 807, 757, 746,
8.32 (dd, J = 8.6, 6.3 Hz, 1 H), 7.36–7.32 (m, 2 H), 7.18–7.15 (m, 2 H),
7.11–7.02 (m, 2 H), 6.84 (dd, J = 8.9, 2.1 Hz, 1 H), 5.93 (s, 1 H), 2.32
(t, J = 7.6 Hz, 2 H), 1.55–1.49 (m, 2 H), 1.35–1.30 (m, 2 H), 0.89 (t,
J = 7.2 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 166.1, 157.7,
149.5, 146.4, 136.5 (d, JC,F = 10.1 Hz), 130.3 (d, JC,F = 10.1 Hz), 128.6,
123.5, 122.7, 119.6 (d, JC,F = 2.9 Hz), 115.2 (d, JC,F = 21.7 Hz), 110.3
(d, JC,F = 21.7 Hz), 101.3 (d, JC,F = 2.9 Hz), 32.7, 28.7, 22.0, 13.8 ppm.
˜
742, 691, 687, 673 cm–1. MS (EI): m/z = 291 [M]+. HRMS (EI): calcd.
for C20H21NO 291.1623; found 291.1628.
(Z)-N-(3-Butyl-1H-isochromen-1-ylidene)-4-fluoroaniline
(3c):
1
Pale yellow oil (45 mg, 77 % yield). H NMR (600 MHz, CDCl3): δ =
8.30 (d, J = 7.6 Hz, 1 H), 7.49 (dd, J = 7.6, 1.4 Hz, 1 H), 7.35 (ddd,
J = 8.2, 7.6, 1.4 Hz, 1 H), 7.19–7.15 (m, 3 H), 7.05–7.00 (m, 2 H), 5.99
(s, 1 H), 2.34 (t, J = 7.2 Hz, 2 H), 1.56–1.50 (m, 2 H), 1.37–1.30 (m, 2
H), 0.90 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (150 MHz, CDCl3): δ =
159.3 (d, JC,F = 241.3 Hz), 156.2, 150.6, 142.6 (d, JC,F = 2.9 Hz), 134.0,
132.3, 127.5, 127.3, 124.6, 124.2 (d, JC,F = 7.2 Hz), 123.2, 115.2 (d,
IR (CHCl3): ν = 3009, 2960, 1674, 1640, 1615, 1593, 1493, 1247,
˜
1167 cm–1. MS (EI): m/z = 295 [M]+. HRMS (EI): calcd. for C19H18NOF
295.1372; found 295.1373.
(Z)-N-(3-Butyl-7-fluoro-1H-isochromen-1-ylidene)aniline (3i):
1
Pale yellow oil (48 mg, 81 % yield). H NMR (600 MHz, CDCl3): δ =
J
C,F = 21.7 Hz), 101.9, 32.7, 28.8, 22.0, 13.8 ppm. IR (CHCl3): ν = 3035,
˜
3010, 1673, 1640, 1503, 810, 761, 695, 685 cm–1. MS (EI): m/z = 295
8.01 (dd, J = 9.6, 2.7 Hz, 1 H), 7.35 (dd, J = 7.6, 7.6 Hz, 2 H), 7.26–
7.15 (m, 4 H), 7.10 (dd, J = 7.6, 6.9 Hz, 1 H), 5.96 (s, 1 H), 2.33 (t, J =
7.6 Hz, 2 H), 1.56–1.50 (m, 2 H), 1.35–1.30 (m, 2 H), 0.90 (t, J = 7.2 Hz,
3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 161.8 (d, JC,F = 245.6 Hz),
155.7 (d, JC,F = 2.9 Hz), 149.5 (d, JC,F = 4.3 Hz), 146.2, 130.5 (d, JC,F
2.9 Hz), 128.6 (d, JC,F = 10.1 Hz), 126.5 (d, JC,F = 7.2 Hz), 125.2 (d,
JC,F = 8.7 Hz), 123.7, 122.8, 120.1 (d, JC,F = 23.1 Hz), 113.4 (d, JC,F
[M]+. HRMS (EI): calcd. for C19H18NOF 295.1372; found 295.1372.
(Z)-4-(tert-Butyl)-N-(3-butyl-1H-isochromen-1-ylidene)aniline
(3d): Pale yellow oil (52 mg, 78 % yield). 1H NMR (600 MHz, CDCl3):
δ = 8.32 (d, J = 7.6 Hz, 1 H), 7.46 (dd, J = 7.6, 1.4 Hz, 1 H), 7.37–7.32
(m, 3 H), 7.21–7.14 (m, 3 H), 5.96 (s, 1 H), 2.36 (t, J = 7.6 Hz, 2 H),
1.59–1.53 (m, 2 H), 1.38–1.30 (m, 11 H), 0.91 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (150 MHz, CDCl3): δ = 156.4, 150.0, 146.3, 143.7, 134.0,
132.0, 127.4, 125.4, 124.5, 123.6, 122.7, 101.7, 34.3, 32.7, 31.5, 28.8,
=
=
24.6 Hz), 100.9, 32.6, 28.8, 22.0, 13.8 ppm. IR (CHCl ): ν = 3035, 2961,
˜
3
2932, 1673, 1641, 1592, 1497, 1328, 1271, 1195, 1153, 1049, 841,
808 cm–1. MS (EI): m/z = 295 [M]+. HRMS (EI): calcd. for C19H18NOF
295.1372; found 295.1382.
22.0, 13.8 ppm. IR (CHCl3): ν = 3035, 3010, 1671, 1235, 1198, 1158,
˜
810, 804, 750, 729, 718, 687, 672 cm–1. MS (EI): m/z = 333 [M]+.
(Z)-N-(3-Butyl-8-fluoro-1H-isochromen-1-ylidene)aniline (3j):
HRMS (EI): calcd. for C23H27NO 333.2093; found 333.2095.
1
Pale yellow oil (49 mg, 83 % yield). H NMR (600 MHz, CDCl3): δ =
7.43 (ddd, J = 8.2, 7.6, 4.8 Hz, 1 H), 7.35–7.32 (m, 2 H), 7.13–7.03 (m,
4 H), 6.95 (d, J = 7.6 Hz, 1 H), 5.94 (s, 1 H), 2.28 (t, J = 7.6 Hz, 2 H),
1.50–1.44 (m, 2 H), 1.32–1.27 (m, 2 H), 0.87 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (150 MHz, CDCl3): δ = 161.5 (d, JC,F = 243.0 Hz), 157.2,
146.7, 146.5 (d, JC,F = 11.6 Hz), 137.2 (d, JC,F = 10.1 Hz), 128.5, 123.4,
122.2, 120.3, 120.3, 115.2 (d, JC,F = 23.1 Hz), 101.3 (d, JC,F = 2.9 Hz),
(Z)-N-(3-Butyl-1H-isochromen-1-ylidene)-2,4,6-trimethylaniline
(3e): Pale yellow oil (50 mg, 79 % yield). H NMR (600 MHz, CDCl3):
1
δ = 8.39 (d, J = 7.6 Hz, 1 H), 7.50 (dd, J = 7.6, 1.4 Hz, 1 H), 7.36 (dd,
J = 7.6, 7.6 Hz, 1 H), 7.18 (d, J = 7.6 Hz, 1 H), 6.86 (s, 2 H), 5.92 (s, 1
H), 2.28 (s, 3 H), 2.23 (t, J = 7.2 Hz, 2 H), 2.09 (s, 6 H), 1.42–1.37 (m,
2 H), 1.27–1.23 (m, 2 H), 0.84 (t, J = 7.6 Hz, 3 H) ppm. 13C NMR
(150 MHz, CDCl3): δ = 156.6, 149.1, 142.5, 134.0, 132.1, 131.4, 128.1,
127.7, 127.5, 127.3, 124.5, 122.9, 101.3, 32.7, 28.5, 21.8, 20.8, 18.2,
32.5, 28.5, 21.9 (d, JC,F = 1.5 Hz), 13.8 ppm. IR (CHCl3): ν = 3009,
˜
1675, 1646, 1592, 1473, 1197, 1157, 810, 662 cm–1. MS (EI): m/z =
295 [M]+. HRMS (EI): calcd. for C19H18NOF 295.1372; found 295.1370.
13.7 ppm. IR (CHCl ): ν = 3008, 2962, 1725, 1710, 1676, 1653, 1487,
˜
3
1468, 1380, 1292, 1238, 724, 718, 678 cm–1. MS (EI): m/z = 319 [M]+.
(Z)-N-(3-Butyl-7-nitro-1H-isochromen-1-ylidene)aniline (3k): Yel-
1
low solid (39 mg, 60 % yield); m.p. 129–130 °C. H NMR (600 MHz,
HRMS (EI): calcd. for C22H25NO 319.1936; found 319.1940.
CDCl3): δ = 9.15 (d, J = 2.1 Hz, 1 H), 8.29 (dd, J = 8.2, 2.1 Hz, 1 H),
(Z)-N-(3-Butyl-1H-isochromen-1-ylidene)-3-methylaniline (3f): 7.37 (dd, J = 7.8, 7.8 Hz, 2 H), 7.29 (d, J = 8.2 Hz, 1 H), 7.22 (d, J =
1
Pale yellow oil (47 mg, 80 % yield). H NMR (600 MHz, CDCl3): δ =
8.31 (d, J = 8.2 Hz, 1 H), 7.48 (d, J = 7.6 Hz, 1 H), 7.35 (dd, J = 7.6,
7.6 Hz, 1 H), 7.25–7.16 (m, 2 H), 7.00 (dd, J = 8.2, 7.6 Hz, 2 H), 6.90
(d, J = 7.6 Hz, 1 H), 5.97 (s, 1 H), 2.36–2.32 (m, 5 H), 1.58–1.52 (m, 2
7.8 Hz, 2 H), 7.14 (dd, J = 7.8 Hz, 1 H), 6.06 (s, 1 H), 2.39 (t, J =
7.6 Hz, 2 H), 1.59–1.54 (m, 2 H), 1.37–1.33 (m, 2 H), 0.91 (t, J = 7.6 Hz,
3 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 160.6, 147.8, 146.7, 145.4,
139.6, 128.7, 126.7, 125.5, 124.3, 124.2, 123.5, 122.8, 101.0, 33.0, 28.6,
H), 1.36–1.31 (m, 2 H), 0.90 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR 22.0, 13.8 ppm. IR (CHCl3): ν = 3035, 3010, 1670, 1646, 1586, 1522,
(150 MHz, CDCl3): δ = 156.3, 150.3, 146.5, 138.2, 134.1, 132.2, 128.3,
127.4, 127.3, 124.5, 124.2, 123.5, 123.3, 119.7, 101.8, 32.8, 28.9, 22.0,
21.5, 13.8 ppm. IR (CHCl3): ν = 3035, 3010, 1673, 1639, 1198, 1158,
˜
1343, 1235, 1160, 852, 810, 766, 747, 692, 687 cm–1. MS (EI): m/z =
322 [M]+. HRMS (EI): calcd. for C19H18N2O3 322.1317; found
322.1318.
˜
Eur. J. Org. Chem. 2016, 541–548
www.eurjoc.org
545
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(Z)-N-(3-Butyl-7-methyl-1H-isochromen-1-ylidene)aniline (3l):
Pale yellow oil (34 mg, 59 % yield). H NMR (600 MHz, CDCl3): δ =
99.2, 55.4 ppm. IR (CHCl3): ν = 3035, 3010, 1603, 1513, 1256, 1234,
˜
1
1179, 810, 789, 772, 705, 693, 687, 673 cm–1. MS (EI): m/z = 327
8.15 (s, 1 H), 7.36–7.30 (m, 3 H), 7.18 (d, J = 7.6 Hz, 2 H), 7.08 (dd,
J = 8.2, 7.6 Hz, 2 H), 5.96 (s, 1 H), 2.42 (s, 3 H), 2.31 (t, J = 7.6 Hz, 2
H), 1.54–1.48 (m, 2 H), 1.36–1.28 (m, 2 H), 0.89 (t, J = 7.6 Hz, 3
H) ppm. 13C NMR (150 MHz, CDCl3): δ = 155.5, 150.8, 146.9, 137.5,
133.4, 131.6, 128.6, 127.2, 124.6, 123.3, 123.1, 122.7, 101.7, 32.6, 28.8,
[M]+. HRMS (EI): calcd. for C22H17NO2 327.1259; found 327.1256.
(Z)-3-[1-(Phenylimino)-1H-isochromen-3-yl]propyl-4-methyl-
benzenesulfonate (3s): Pale yellow oil (79 mg, 91 % yield). 1H NMR
(600 MHz, CDCl3): δ = 8.30 (d, J = 7.6 Hz, 1 H), 7.74 (d, J = 6.9 Hz, 2
H), 7.51 (dd, J = 7.6, 7.6 Hz, 1 H), 7.38 (dd, J = 7.6, 7.6 Hz, 1 H), 7.33–
7.28 (m, 4 H), 7.15 (d, J = 7.6 Hz, 1 H), 7.10–7.05 (m, 3 H), 5.92 (s, 1
H), 3.99 (t, J = 5.5 Hz, 2 H), 2.41 (s, 3 H), 2.41–2.39 (m, 2 H), 1.89–
1.84 (m, 2 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 153.7, 149.9,
146.5, 144.9, 133.6, 132.8, 132.3, 129.9, 128.7, 127.9, 127.8, 127.4,
124.8, 123.5, 123.3, 122.4, 102.9, 69.0, 29.1, 25.9, 21.7 ppm. IR
22.0, 21.3, 13.8 ppm. IR (CHCl ): ν = 2960, 2932, 1672, 1641, 1635,
˜
3
1616, 1592, 1502, 1485, 1236, 1207, 1177, 1157, 842, 743, 725,
686 cm–1. MS (EI): m/z = 291 [M]+. HRMS(EI): calcd. for C20H21NO
291.1623; found 291.1628.
(Z)-N-(3-Butyl-7-methoxy-1H-isochromen-1-ylidene)aniline
(3m): Pale yellow oil (52 mg, 84 % yield). 1H NMR (600 MHz, CDCl3): (CHCl ): ν = 3034, 1674, 1235, 1176, 810, 798, 785, 736, 712, 690,
˜
3
δ = 7.81 (s, 1 H), 7.34 (dd, J = 7.6, 7.6 Hz, 2 H), 7.19 (d, J = 7.6 Hz,
2 H), 7.12–7.07 (m, 3 H), 5.94 (s, 1 H), 3.90 (s, 3 H), 2.31 (t, J = 7.2 Hz,
2 H), 1.53–1.50 (m, 2 H), 1.34–1.30 (m, 2 H), 0.89 (t, J = 7.2 Hz, 3
H) ppm. 13C NMR (150 MHz, CDCl3): δ = 159.1, 154.3, 150.7, 146.9,
128.6, 127.7, 126.1, 124.3, 123.3, 122.8, 121.5, 108.7, 101.3, 55.7, 32.5,
686, 678, 661 cm–1. MS (EI): m/z = 433 [M]+. HRMS (EI): calcd. for
C25H23NO4S: 433.1348; found 433.1352.
(Z)-N-(3-Cyclohexyl-1H-isochromen-1-ylidene)aniline (3t): Pale
1
yellow oil (56 mg, 92 % yield). H NMR (600 MHz, CDCl3): δ = 8.32
(d, J = 7.6 Hz, 1 H), 7.48 (dd, 1 H, 7.6, 1.4 Hz), 7.37–7.33 (m, 3 H),
7.20–7.06 (d, J = 7.6, 1.4 Hz, 3 H), 7.10–7.06 (m, 1 H), 5.95 (s, 1 H),
2.26–2.21 (m, 1 H), 1.86 (m, 2 H), 1.76 (m, 2 H), 1.68–1.65 (m, 1 H),
1.33–1.22 (m, 4 H), 1.17–1.12 (m, 1 H) ppm. 13C NMR (150 MHz,
CDCl3): δ = 160.4, 150.4, 146.7, 134.2, 132.2, 128.5, 127.4, 127.3,
124.8, 123.4, 123.3, 122.8, 99.8, 41.5, 30.4, 25.9, 25.8 ppm. IR (CHCl3):
28.9, 22.0, 13.8 ppm. IR (CHCl ): ν = 3009, 2961, 2934, 1673, 1638,
˜
3
1632, 1613, 1592, 1501, 1466, 1347, 1279, 1237, 1197, 1153, 1057,
1033, 843, 808, 685 cm–1. MS (EI): m/z = 307 [M]+. HRMS (EI): calcd.
for C20H21NO2 307.1572; found 307.1572.
(Z)-N-(5-Butyl-7H-thieno[2,3-c]pyran-7-ylidene)aniline (3n): Pale
yellow oil (49 mg, 86 % yield). 1H NMR (600 MHz, C6D6): δ = 7.48
ν = 2934, 2857, 1669, 1642, 1631, 1605, 1593, 1490, 1236, 1160,
˜
(dd, J = 8.2, 1.4 Hz, 2 H), 7.27 (dd, J = 8.2, 7.6 Hz, 2 H), 6.98 (d, J = 1061, 699, 686 cm–1. MS (EI): m/z = 303 [M]+. HRMS (EI): calcd. for
7.6 Hz, 1 H), 6.77 (d, J = 5.2 Hz, 1 H), 6.42 (d, J = 5.2 Hz, 1 H), 5.55
(s, 1 H), 1.93 (t, J = 7.6 Hz, 2 H), 1.32–1.26 (m, 2 H), 1.07–1.02 (m, 2
H), 0.73 (t, J = 7.2 Hz, 3 H) ppm. 13C NMR (150 MHz, C6D6): δ =
159.0, 147.8, 142.2, 133.0, 129.7, 129.1, 128.9, 128.7, 124.6, 124.5,
C21H21NO 303.1623; found 303.1629.
(Z)-N-(3-Cyclohexyl-7-nitro-1H-isochromen-1-ylidene)-4-fluoro-
aniline (3u): Yellow prisms (45 mg, 61 % yield); m.p. 158–159 °C.
1H NMR (600 MHz, CDCl3): δ = 9.04 (s, 1 H), 8.21 (dd, J = 8.9, 1.4 Hz,
1 H), 7.22 (d, J = 8.9 Hz, 1 H), 7.14 (d, J = 8.9 Hz, 2 H), 6.98 (d, J =
8.9 Hz, 2 H), 5.97 (s, 1 H), 2.25–2.21 (m, 1 H), 1.84–1.82 (m, 2 H),
1.75–1.73 (m, 2 H), 1.66–1.63 (m, 1 H), 1.29–1.08 (m, 5 H) ppm. 13C
99.8, 33.4, 29.9, 22.9, 14.6 ppm. IR (CHCl ): ν = 3035, 3010, 1664,
˜
3
1620, 1591, 1486, 1235, 810, 687 cm–1. MS (EI): m/z = 283 [M]+.
HRMS (EI): calcd. for C17H17NOS 283.1031; found 283.1036.
(Z)-N-[3-(4-Fluorophenyl)-1H-isochromen-1-ylidene]aniline (3o): NMR (150 MHz, CDCl3): δ = 164.4, 159.7 (d, JC,F = 242.8 Hz), 148.1,
Pale yellow solid (20 mg, 31 % yield); m.p. 156–157 °C. 1H NMR
(600 MHz, CDCl3): δ = 8.37 (d, J = 7.6 Hz, 1 H), 7.56–7.53 (m, 3 H),
7.43–7.38 (m, 3 H), 7.32 (d, J = 7.6 Hz, 1 H), 7.22 (d, J = 7.6 Hz, 2 H),
7.14 (dd, J = 7.6, 7.6 Hz, 1 H), 7.02 (dd, J = 8.9, 7.6 Hz, 2 H), 6.64 (s,
1 H) ppm. 13C NMR (150 MHz, CDCl3): δ = 163.4 (d, JC,F = 250.0 Hz),
150.5, 149.6, 146.8, 133.8, 132.5, 128.8, 128.6 (d, JC,F = 2.9 Hz), 128.2,
127.5, 126.6, (d, JC,F = 8.7 Hz), 125.6, 123.7, 123.5, 122.3, 115.8 (d,
146.7, 141.3 (d, JC,F = 2.9 Hz), 139.6, 126.6, 125.8, 124.5 (d, JC,F =
8.7 Hz), 124.3, 123.3, 115.3 (d, JC,F = 21.7 Hz), 99.3, 41.9, 30.3, 29.7,
25.8 (d, J = 4.3 Hz) ppm. IR (CHCl3): ν = 2935, 1667, 1641, 1610,
˜
1584, 1522, 1503, 1341, 1160, 1152, 1100, 851, 842, 710, 684 cm–1
.
MS (EI): m/z = 366 [M]+. HRMS (EI): calcd. for C21H19N2O3F 366.1380;
found 366.1374.
(Z)-N-(3-Cyclohexyl-7-nitro-1H-isochromen-1-ylidene)aniline
(3v): Yellow solid (39 mg, 55 % yield); m.p. 137–138 °C. 1H NMR
(600 MHz, CDCl3): δ = 9.15 (dd, J = 2.1 Hz, 1 H), 8.29 (dd, J = 8.6,
2.1 Hz, 1 H), 7.37 (dd, J = 7.6, 7.6 Hz, 2 H), 7.29 (d, J = 8.6 Hz, 1 H),
7.22 (d, J = 7.6 Hz, 2 H), 7.14 (dd, J = 7.6, 7.6 Hz, 1 H), 6.03 (s, 1 H),
2.30–2.29 (m, 1 H), 1.91–1.88 (m, 2 H), 1.81–1.78 (m, 2 H), 1.71–1.68
JC,F = 21.7 Hz), 100.6 ppm. IR (CHCl ): ν = 3035, 3010, 1662, 1629,
˜
3
1594, 1510, 1490, 1341, 1271, 1238, 1160, 1015, 844, 822, 810, 692,
687 cm–1. MS (EI): m/z = 315 [M]+. HRMS (EI): calcd. for C21H14NOF
315.1059; found 315.1056.
(Z)-N-[3-(p-Tolyl)-1H-isochromen-1-ylidene]aniline (3q): Pale yel-
1
low oil (52 mg, 84 % yield). H NMR (600 MHz, CDCl3): δ = 8.37 (d, (m, 1 H), 1.36–1.25 (m, 4 H), 1.19–1.14 (m, 1 H) ppm. 13C NMR
J = 7.6 Hz, 1 H), 7.53 (dd, J = 7.6, 7.6 Hz, 1 H), 7.46 (d, J = 7.6 Hz, 2 (150 MHz, CDCl3): δ = 164.5, 147.9, 146.7, 145.4, 139.8, 128.7, 126.6,
H), 7.41–7.37 (m, 3 H), 7.30 (d, J = 7.6 Hz, 1 H), 7.24 (d, J = 8.2 Hz,
2 H), 7.13 (d, J = 7.6 Hz, 3 H), 6.66 (s, 1 H), 2.33 (s, 3 H) ppm. 13C
NMR (150 MHz, CDCl3): δ = 151.9, 149.9, 146.9, 139.7, 134.1, 132.4,
125.7, 124.3, 124.2, 123.4, 122.8, 99.1, 41.9, 30.3, 25.8, 25.8 ppm. IR
(CHCl ): ν = 2935, 2858, 1667, 1642, 1593, 1522, 1452, 1341, 1254,
˜
3
1235, 1160, 1100, 970, 851, 810, 687 cm–1. MS (EI): m/z = 348 [M]+.
129.6, 129.3, 129.4, 128.7, 127.9, 127.5, 125.5, 124.6, 123.5, 122.5, HRMS (EI): calcd. for C21H20N2O3 348.1474; found 348.1477.
100.1, 21.3 ppm. IR (CHCl ): ν = 3035, 3010, 1661, 1626, 1593, 1235,
˜
3
(Z)-N-(3-Cyclohexyl-7-nitro-1H-isochromen-1-ylidene)-4-methyl-
814, 810, 772, 693 cm–1. MS (EI): m/z = 311 [M]+. HRMS (EI): calcd.
aniline (3w): Yellow prisms (49 mg, 67 % yield); m.p. 138–139 °C.
for C22H17NO 311.1310; found 311.1304.
1H NMR (600 MHz, CDCl3): δ = 9.12 (d, J = 2.8 Hz, 1 H), 8.26 (dd, J =
(Z)-N-[3-(4-Methoxyphenyl)-1H-isochromen-1-ylidene]aniline
(3r): Pale yellow oil (52 mg, 80 % yield). H NMR (600 MHz, CDCl3):
δ = 8.36 (d, J = 7.6 Hz, 1 H), 7.55–7.50 (m, 3 H), 7.40–7.37 (m, 3 H),
7.30 (d, J = 7.6 Hz, 1 H), 7.24 (d, J = 7.6 Hz, 2 H), 7.13 (dd, J = 7.6,
7.6 Hz, 1 H), 6.87–6.84 (m, 2 H), 6.59 (s, 1 H), 3.81 (s, 3 H) ppm. 13C
NMR (150 MHz, CDCl3): δ = 160.7, 151.7, 150.0, 147.0, 134.3, 132.4,
8.9, 2.8 Hz, 1 H), 7.27 (d, J = 8.9 Hz, 1 H), 7.18–7.16 (m, 4 H), 6.01 (s,
1 H), 2.37 (s, 3 H), 2.33–2.28 (m, 1 H), 1.93–1.91 (m, 2 H), 1.82–1.79
(m, 2 H), 1.73–1.69 (m, 1 H), 1.38–1.26 (m, 4 H), 1.19–1.16 (m, 1
H) ppm. 13C NMR (150 MHz, CDCl3): δ = 164.5, 147.4, 146.6, 142.5,
139.7, 133.9, 129.2, 126.4, 125.6, 124.6, 123.3, 123.2, 99.1, 41.9, 30.3,
1
25.8, 25.8, 21.1 ppm. IR (CHCl ): ν = 2935, 1663, 1640, 1698, 1584,
˜
3
128.8, 127.7, 127.4, 126.2, 125.4, 125.0, 123.5, 123.3, 122.4, 114.1, 1507, 1452, 1341, 1254, 1159, 1099, 1056, 1018, 851, 799, 736, 714,
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693, 687 cm–1. MS (EI): m/z = 362 [M]+. HRMS (EI): calcd. for
C22H22N2O3 362.1630; found 362.1628.
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Acknowledgments
The authors gratefully acknowledge the Japanese Society for
the Promotion of Science (JSPS), KAKENHI for a Grant-in-Aid for
Scientific Research (C) (grant 26460025 to R. Y.). Dr. M. Yamagu-
chi (Setsunan University) is thanked for obtaining low-resolu-
tion mass spectrometry (LRMS) and HRMS data.
[10]
Keywords: Heterocycles · Domino reactions · Copper ·
Hypervalent compounds · Cyclization
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Received: October 16, 2015
Published Online: December 7, 2015
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim