Domino access to yne-functionalized benzoisoindolines from triynes

Article abstract of DOI:10.1055/s-0033-1341045

The first examples of a convenient domino synthesis of fused yne-functionalized benzoisoindoline derivatives by a copper(I) iodide catalyzed cyclization reaction of simple triynes in a single operation are described. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1341045

PAPER
▌1547
paper
Domino Access to Yne-Functionalized Benzoisoindolines from Triynes
Domino Access to Yne-Functionalized Benzoisoindolines
Lidong Li,a,b Qiong Hu,a Pingping Zhou,a Haifeng Xie,a Xiaorong Zhang,a Hao Zhang,a Hua Wang,a Yimin Hu*a
a
Laboratory of Functional Molecular Solids, Ministry of Education; Anhui Key Laboratory of Molecular-Based Materials, School of Chemistry
and Materials Science, Anhui Normal University, Wuhu, Anhui 241000, P. R. of China
Fax +86(553)3883517; E-mail: yiminhu@mail.ahnu.edu.cn
b
Yancheng Institute of Technology, School of Chemical and Biological Engineering, Yancheng, Jiangsu 224051, P. R. of China
Received: 16.01.2014; Accepted after revision: 26.02.2014
tions of 1,ω-diynes suffers from several limitations.7 An
Abstract: The first examples of a convenient domino synthesis of
efficient strategy involving a sequence of domino8 ortho-
fused yne-functionalized benzoisoindoline derivatives by a cop-
functionalization reactions was developed by Lautens and
per(I) iodide catalyzed cyclization reaction of simple triynes in a
single operation are described.
co-workers9 for the synthesis of various benzo[c]phenan-
thridines. We have previously used the domino strategy to
Key words: heterocycles, domino reactions, cycloadditions, catal-
devise alternative processes for the efficient construction
of benzocyclopenta- to benzylcyclooctaisoindoles.10
Porco and co-workers have developed an efficient a sil-
ver-catalyzed cycloisomerization/dipolar cycloaddition to
give pyrroloisoquinoline compounds that are related to
the lamellarin alkaloids.11 Sanford and co-workers report-
ed that the reactivity of high-valent organocopper(III)
species is of direct relevance to copper catalysis.12
ysis, copper
Conjugated alkynes are basic building blocks for many
natural products, pharmaceuticals, agrochemicals, and
materials for optics and electronics.1 The diverse range of
reactivities of yne-functionalized pyrroles and indoles has
been extensively investigated.2 Yne-functionalized π-con-
jugated molecules have been prepared by alkynylation re-
actions with alkynylmetal reagents or by direct
alkynylation with terminal alkynes.3 Saá4 and Kawano5
and their respective co-workers reported a thermal de-
hydro-Diels–Alder reaction of triynes to produce diaryl-
acetylenes (Scheme 1).
We envisioned an interesting isoindoline synthesis by a
copper(I)-catalyzed [4+2]-type cycloaddition reaction of
triyne substrates 1a–w (Scheme 1). First, we optimized
the reaction conditions by studying the reaction of triyne
1a in a series of test experiments (Table 1). Altering the
experimental conditions showed that the yield of the mul-
ticascade reaction to give benzoindole 2a was markedly
affected by the temperature (Table 1, entries 2–5), the cat-
alytic system (entries 13–15), and the solvent (entries 10–
12). The highest yield (81%) of 4-(phenylethynyl)-2-to-
syl-2,3-dihydro-1H-benzo[f]isoindole (2a) was obtained
by the reaction of triyne 1a in acetonitrile in the presence
of a catalytic amount of copper(I) iodide at 90 °C for
60 hours. Having identified these optimal conditions, we
performed subsequent studies on triynes 1 (1 equiv) in the
presence of 10 mol% copper(I) iodide catalyst as an addi-
tive in acetonitrile at 90 °C.
R
Y
X
R
Y
heat
X
Saá (2000)
Kawano (2006)
thermal dehydro-Diels–Alder
R2
R2
CuI
PG
N
this paper
R1
Illustrative examples of the scope of this reaction are
shown in Table 2. Various triynes of a similar structure to
1a with various substituents were found to be compatible
with this copper-catalyzed domino reaction and gave the
PG
N
R1
Scheme 1 Example of a hexadehydro-Diels–Alder reaction and a
retrosynthetic analysis for yne-functionalized benzoisoindolines
corresponding
alkynyl-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindoles in good to excellent yields, apart from 2r
(Table 1, entry 18) and 2l (entry 12). Among the substitu-
ents that we examined were fluoro, chloro, methyl, meth-
oxy groups in the terminal position of the diyne arm and
various substituents on the benzene ring. The yne-func-
tionalized benzoisoindoline cascade can be considered in
two groups. In the first group, the triyne substrates 1a–f,
which had no substituent on the benzene ring (R1 = H) and
various terminal R2 groups, gave 2a–f. respectively (en-
tries 1–6). The yield of benzo[f]isoindoline 2c was the
highest (85%) among this group (entry 3), and the other
desired benzo[f]isoindolines were obtained in good yields
Lee and co-workers developed catalytic alkane C–H in-
sertion reactions to give C–C bonds, thereby permitting
the conversion of tetraynes into yne-functionalized tricy-
clic compound.6 Although fully intramolecular [2+2+2]
or [4+2] cycloaddition reactions are generally excellent
and efficient processes for preparing fused heterocycles,
expanding the scope of the substrates to include the reac-
SYNTHESIS 2014, 46, 1547–1554
Advanced online publication: 24.03.2014
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1341045; Art ID: SS-2014-F0029-OP
© Georg Thieme Verlag Stuttgart · New York

1548
L. Li et al.
PAPER
structure and relative configuration of 2h was confirmed
by X-ray diffraction (Figure 1).13 Further details are pro-
vided in the Supporting Information.
Table 1 Optimization of the Conditions for the One-Step Cascade
Reaction
Ts
N
Ts
N
1a
2a
Entry Catalyst
(mol%)
Solvent
Time
(h)
Temp Yielda
(°C)
(%)
1
2
CuI (5)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
toluene
THF
60
60
60
60
60
60
24
48
72
60
60
60
60
60
60
90
50
70
90
100
90
90
90
90
90
90
90
90
90
90
36
0
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (15)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
PdCl2(10)
Pd(OAc)2 (10)
AgNO3 (10)
3
38
81
80
81
47
73
81
56
75
34
trace
35
72
4
5
6
7
8
Figure 1 Molecular structure of compound 2h. Ellipsoids are drawn
at 30% probability. Selected bond lengths and angles: C9–C10
1.365(3) Å, C9–C18 1.407(3) Å, C16–C17 1.439(3) Å, C17–C18
1.376(3) Å, C20–C21 1.194(3) Å, C9–C17–C18 121.8(2)°, C10–C9–
C18 120.9(2)°, C10–C11–C16 120.0(2)°, C11–C16–C17 119.2(2)°,
and C16–C17–C18 118.4(2)°.
9
10
11
12
13
14
15
DMF
A plausible mechanism for the formation of fused yne-
functionalized benzoisoindoline is shown in Scheme 2.
Reversible coordination of copper to the triyne moiety in
MeCN
MeCN
MeCN
Ph
of 64–83%. In the second group, the triyne substrates 1a,
1g, 1m, 1s, and 1v (entries 1, 7, 13, 19, and 22, respective-
ly) all had the same R2 group (R2 = Ph) but different R1
substituents; in these cases, the yields of products were
similar to those of 1a–f (68–81%).
Cu
Ts
N
B
We also examined the effects of substituents on the phen-
ylacetylene moiety. Overall, the results showed that prod-
ucts in which the benzene rings was substituted with
electron-donating groups (2n, 2o, 2u, and 2v; entries 14,
15, 21, and 22, respectively) were obtained in much high-
er yields than those with electron-withdrawing substitu-
ents (2e, 2j, 2k, and 2s; entries 5, 10, 11, and 19). Note
that the compound 2r (65%; entry 17) was obtained in the
lowest yield among the desired products. No significant
difference was found between the yields of compounds 2l
and 2q (62% and 64%; entries 13 and 17). These results
suggest that it is difficult to evaluate the contribution of
the electronic effect in two different benzene rings.
Ph
Cu
Ts
N
Cu
Ts
N
C
A
Ph
Ts
N
Cu
N
Ts
The structures of all of the resulting fused phenanthridine
compounds were confirmed by various spectroscopic
techniques (1H and 13C NMR, UV, and IR spectroscopy
and high-resolution mass spectrometry). The molecular
2
1
Scheme 2 Proposed catalytic cycle
Synthesis 2014, 46, 1547–1554
© Georg Thieme Verlag Stuttgart · New York

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Domino Access to Yne-Functionalized Benzoisoindolines
1549
1 gives intermediate B, which is stabilized by coordina- ate more-interesting structures for biological studies. We
tion of the copper atom with the neighboring η3-propargyl intend to perform further studies in an attempt to elucidate
moiety. Reductive elimination of copper from B gives the the nature of this catalytic transformation. We are also
strained cyclic cumulene C, which undergoes sigmatropic evaluating the process with a broader scope of substrates
rearrangement to give the cross-annulation product 2.
and we will attempt to synthesize heterocycles with more-
complex π-systems.
In conclusion, we have developed a practical and efficient
domino method for the preparation of various fused yne-
functionalized benzoisoindolines from triynes through a
copper(I)-catalyzed [4+2]-type cycloaddition. This meth-
od produces yne-functionalized benzoisoindoline deriva-
tives with excellent regioselectivities in moderate to good
yields. This method will contribute to our efforts to gener-
All the catalytic reactions were performed under argon in oven-
dried Schlenk flasks. The chemicals were purchased from Alfa Ae-
sar and Acros Organics. All solvents and materials were dried, re-
distilled, or recrystallized before use. 1H NMR (300 MHz) and 13
C
NMR (75 MHz) spectra were recorded on a Bruker Avance 300
Table 2 Copper(I)-Catalyzed One-Pot Reaction for the Formation of Various Yne-Functionalized Benzoisoindoles
R2
O
S
O
S
CuI
R1
N
N
MeCN, 90 °C
O
O
R1
R2
1
2
Entrya
Product
R1
R2
Ph
Yieldb (%)
1
2
2a
2b
2c
2d
2e
2f
H
81
83
85
71
73
64
76
77
81
69
70
62
74
78
82
66
64
52
68
71
84
79
81
H
4-MeC6H4
4-EtC6H4
4-FC6H4
4-ClC6H4
4-MeOC6H4
Ph
3
H
4
H
5
H
6
H
7
2g
2h
2i
6-F
6-F
6-F
6-F
6-F
6-F
8-Me
8-Me
8-Me
8-Me
8-Me
8-Me
6-Cl
6-Cl
6-Me
6-OMe
H
8
4-MeC6H4
4-EtC6H4
4-FC6H4
4-ClC6H4
4-MeOC6H4
Ph
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2j
2k
2l
2m
2n
2o
2p
2q
2r
2s
4-MeC6H4
4-EtC6H4
4-FC6H4
4-ClC6H4
4-MeOC6H4
Ph
2t
4-MeC6H4
4-MeC6H4
Ph
2u
2v
2w
Bu
a Reaction conditions: 1a–v (1.0 equiv), CuI (10 mol%), MeCN (10 mL), 90 °C, 60 h.
b Isolated yields after flash column chromatography.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1547–1554

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L. Li et al.
PAPER
spectrometer with CDCl3 as the solvent. Chemical shifts are report-
ed in ppm relative to TMS for the 1H NMR spectra (0.00 ppm) and
to CDCl3 for the 13C spectra (77.0 ppm). Column chromatography
was performed on 300–400 mesh silica gel. Melting points were de-
termined by using a Gallenkamp melting point apparatus and are
uncorrected. The Fourier-transform IR spectra were recorded with
KBr pellets or thin film in CHCl3 on a NaCl window in the range
4000–400 cm–1 on a Nicolet 5DX spectrometer. All HRMS spectra
were record in the EI or APCI mode at 70 eV.
1H NMR (300 MHz, CDCl3): δ = 8.32–8.35 (d, J = 8.7 Hz, 1 H,
ArH), 7.77–7.85 (m, 3 H, ArH), 7.34–7.58 (m, 5 H, ArH), 7.28–7.32
(d, J = 10.8 Hz, 2 H, ArH), 7.25–7.26 (d, J = 3.3 Hz, 2 H, ArH),
4.89 (s, 2 H, NCH2), 4.78 (s, 2 H, NCH2), 2.68–2.76 (m, 2 H,
ArCH2CH3), 2.39 (s, 3 H, ArCH3), 1.26–1.31 (t, J = 7.8 Hz, 2 H,
ArCH2CH3).
13C NMR (75.5 MHz, CDCl3): δ = 145.5, 143.8, 138.1, 134.1,
133.4, 133.0, 132.7, 131.8, 129.9, 128.2, 128.1, 127.7, 126.8, 126.5,
125.8, 121.4, 119.9, 115.4, 99.5, 83.6, 53.8, 53.8, 29.0, 21.6, 15.5.
X-ray crystallography diffraction data for 2h were collected at r.t.
with a Bruker SMART APEX CCD diffractometer with graphite-
monochromated Mo-Kα radiation (λ = 0.71073 Å) in the ω-scan
mode. Data reductions and absorption corrections were performed
with SAINT and SADABS software, respectively.15 The structure
was solved by direct methods and refined on F2 by full-matrix least-
squares using SHELXTL.16 All nonhydrogen atoms were treated
anisotropically. The positions of hydrogen atoms were generated
geometrically.
HRMS (APCI): m/z [M + H]+ calcd for C29H26NO2S: 452.1679;
found: 452.1675.
4-[(4-Fluorophenyl)ethynyl)]-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2d)
White solid; yield: 314 mg (71%); mp 188–189 °C; Rf = 0.48 (PE–
EtOAc, 6:1).
FTIR (neat): 3049.5, 3026.3, 2962.7, 2920.2, 2860.4, 1597.1,
1508.3, 1460.1, 1346.3, 1313.5, 1215.2, 1157.3, 1095.6, 1055.1,
1016.5, 837.1, 815.9, 752.2, 709.8, 663.5 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.29–8.32 (d, J = 7.8 Hz, 1 H,
ArH), 7.77–7.85 (m, 3 H, ArH), 7.50–7.65 (m, 5 H, ArH), 7.10–7.35
(m, 4 H, ArH), 4.89 (s, 2 H, NCH2), 4.78 (s, 2 H, NCH2), 2.39 (s, 3
H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.9, 138.4, 135.2, 134.2,
133.4, 133.0, 132.6, 129.9, 128.9, 128.3, 128.3, 127.7, 127.0, 126.6,
125.6, 121.9, 121.2, 114.8, 97.6, 85.2, 53.7, 53.4, 21.6.
4-(Phenylethynyl)-2-tosyl-2,3-dihydro-1H-benzo[f]isoindole
(2a):Typical Procedure
Triyne 1a (1.0 equiv) and CuI (10 mol%) were added to degassed
MeCN (5 mL). The mixture was stirred at r.t. for 30 min then heated
to 90 °C for 60 h. The mixture was then cooled and the reaction was
quenched with H2O (5 mL). The mixture was extracted with EtOAc
(30 mL) and the organic layers were combined and washed succes-
sively with 5% aq HCl (6 mL), 5% aq Na2CO3 (6 mL), and sat. aq
NaCl (6 mL) then dried (MgSO4) and concentrated. The residue was
purified by flash column chromatography (silica gel, PE–EtOAc,
6:1) to give a white solid; yield: 343 mg (81%); mp 211–212 °C;
Rf = 0.48 (PE–EtOAc, 6:1).
HRMS (APCI): m/z [M + H]+ calcd for C27H21FNO2S: 442.1272;
found: 442.1264.
4-[(4-Chlorophenyl)ethynyl)]-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2e)
White solid; yield: 334 mg (73%); mp 203–204 °C; Rf = 0.48 (PE–
EtOAc, 6:1).
FTIR (neat): 3051.4, 2941.4, 2856.6, 1597.1, 1491.0, 1444.7,
1346.3, 1159.2, 1101.4, 1072.4, 1018.4, 887.3, 750.3, 671.2 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.34–8.38 (d, J = 7.8 Hz, 1 H,
ArH), 7.80–7.88 (m, 3 H, ArH), 7.29–7.69 (m, 10 H, ArH), 4.93 (s,
2 H, NCH2), 4.82 (s, 2 H, NCH2), 2.43 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.9, 138.3, 134.1, 133.4,
133.0, 132.7, 131.8, 129.4, 128.9, 128.6, 128.2, 127.7, 126.9, 126.6,
125.7, 122.7, 121.6, 115.1, 99.3, 84.3, 54.1, 53.7, 21.6.
FTIR (neat): 3061.0, 3032.1, 2955.0, 2922.2, 2856.6, 1597.1,
1489.1, 1454.3, 1398.4, 1346.3, 1311.6, 1159.2, 1089.8, 1060.9,
1014.6, 885.3, 821.7, 775.4, 748.4, 707.9, 669.3 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.29–8.31 (d, J = 7.8 Hz, 1 H,
ArH), 7.78–7.85 (m, 3 H, ArH), 7.50–7.61 (m, 5 H, ArH), 7.26–7.42
(m, 4 H, ArH), 4.89 (s, 2 H, NCH2), 4.78 (s, 2 H, NCH2), 2.40 (s, 3
H, ArCH3).
HRMS (APCI): m/z [M + H]+ calcd for C27H22NO2S: 424.1329;
found: 424.1322.
13C NMR (75.5 MHz, CDCl3): δ = 143.9, 138.4, 135.0, 134.2,
133.4, 133.0, 132.6, 129.9, 128.9, 128.3, 127.7, 127.0, 126.6, 125.6,
121.9, 121.2, 114.8, 97.9, 85.1, 53.7, 21.6.
4-(4-Tolylethynyl)-2-tosyl-2,3-dihydro-1H-benzo[f]isoindole
(2b)
White solid; yield: 363 mg (83%); mp 186–187 °C; Rf = 0.48 (PE–
EtOAc, 6:1).
HRMS (APCI): m/z [M + H]+ calcd for C27H21ClNO2S: 458.0976;
found: 458.0972.
FTIR (neat): 3063.0, 3028.2, 2955.0, 2918.3, 2856.6, 1599.0,
1510.3, 1454.3, 1398.4, 1346.3, 1159.2, 1101.3, 1066.6, 1018.4,
883.4, 812.0, 746.5, 669.3 cm–1.
4-[(4-Methoxyphenyl)ethynyl]-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2f)
1H NMR (300 MHz, CDCl3): δ = 8.32–8.35 (d, J = 7.8 Hz, 1 H,
ArH), 7.76–7.85 (m, 3 H, ArH), 7.48–7.57 (m, 5 H, ArH), 7.32–8.34
(d, J = 7.8 Hz, 2 H, ArH), 7.23–7.26 (t, J = 8.1 Hz, 2 H, ArH), 4.89
(s, 2 H, NCH2), 4.78 (s, 2 H, NCH2), 2.43 (s, 3 H, ArCH3), 2.39 (s,
3 H, ArCH3).
White solid; yield: 290 mg (64%); mp 159–160 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
FTIR (neat): 3051.4, 3030.2, 2956.9, 2922.2, 2854.7, 1604.8,
1512.2, 1462.0, 1398.4, 1346.3, 1290.4, 1249.9, 1159.2, 1099.4,
1026.1, 829.4, 808.2, 665.4 cm–1.
13C NMR (75.5 MHz, CDCl3): δ = 143.8, 139.2, 138.1, 134.1,
133.5, 133.0, 132.7, 131.7, 130.1, 129.9, 129.3, 128.6, 128.2, 127.7,
126.8, 126.5, 125.8, 121.4, 99.5, 83.6, 53.8, 53.3, 21.6, 21.5.
HRMS (APCI): m/z [M + H]+ calcd for C28H24NO2S: 438.1522;
found: 438.1517.
1H NMR (300 MHz, CDCl3): δ = 8.32–8.34 (d, J = 7.8 Hz, 1 H,
ArH), 7.76–7.85 (m, 3 H, ArH), 7.50–7.60 (m, 5 H, ArH), 7.31–7.34
(d, J = 7.8 Hz, 2 H, ArH), 6.94–6.97 (d, J = 9.0 Hz, 2 H, ArH),, 4.89
(s, 2 H, NCH2), 4.78 (s, 2 H, NCH2), 3.88 (s, 3 H, -OCH3), 2.39 (s,
3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 160.1, 143.8, 137.9, 134.1,
133.5, 133.3, 133.0, 132.6, 132.3, 129.9, 128.2, 127.7, 126.7, 126.5,
125.8, 121.2, 114.8, 114.2, 99.3, 83.0, 55.4, 53.8, 53.7, 21.5.
4-[(4-Ethylphenyl)ethynyl]-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2c)
White solid; yield: 383 mg (85%); mp 213–214 °C; Rf = 0.48 (PE–
EtOAc, 6:1).
HRMS (APCI): m/z [M + H]+ calcd for C28H24NO3S: 454.1471;
found: 454.1461.
FTIR (neat): 3059.1, 2924.1, 2841.2, 1597.1, 1489.1, 1309.7,
1103.3, 1014.6, 873.8, 775.4, 748.4, 669.3 cm–1.
Synthesis 2014, 46, 1547–1554
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Domino Access to Yne-Functionalized Benzoisoindolines
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6-Fluoro-4-(phenylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2g)
White solid; yield: 327 mg (74%); mp 222–224 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
1093.6, 1074.4, 1016.5, 889.2, 871.8, 831.3, 790.8, 706.0, 669.3
cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.81–7.84 (d, J = 6.6 Hz, 1 H,
ArH), 7.75–7.81 (m, 3 H, ArH), 7.59–7.64 (m, 3 H, ArH), 7.32–7.34
(d, J = 7.8 Hz, 3 H, ArH), 7.10–7.16 (t, J = 8.7 Hz, 2 H, ArH), 4.87
(s, 2 H, NCH2), 4.76 (s, 2 H, NCH2), 2.39 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 164.6, 163.1, 143.9, 139.3,
133.8, 133.7, 130.7, 130.5, 129.9, 127.7, 121.6, 119.6, 117.1, 116.8,
116.1, 115.8, 109.6, 109.3, 98.4, 83.3, 53.7, 53.6, 21.5.
FTIR (neat): 3074.5, 3028.2, 2943.4, 2924.1, 2858.5, 1597.1,
1506.4, 1444.7, 1344.4, 1317.4, 1240.2, 1159.2, 1097.5, 1070.5,
885.3, 792.7, 758.0, 671.2 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.74–7.76 (d, J = 7.2 Hz, 2 H,
ArH), 7.31–7.35 (m, 3 H, ArH), 7.20 (s, 3 H, ArH), 6.91–6.97 (t,
J = 9.6 Hz, 5 H, ArH), 4.72 (s, 2 H, NCH2), 4.48 (s, 2 H, NCH2),
2.43 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 163.1, 143.9, 133.4, 131.8,
133.0, 129.6, 129.1, 128.6, 128.0, 127.7, 127.2, 121.5, 117.1, 116.7,
115.7, 115.4, 109.7, 109.4, 99.6, 83.6, 53.7, 53.6, 21.6.
HRMS (APCI): m/z [M + H]+ calcd for C27H20F2NO2S: 460.1177;
found: 460.1172.
4-[(4-Chlorophenyl)ethynyl]-6-fluoro-2-tosyl-2,3-dihydro-1H-
benzo[f]isoindole (2k)
White solid; yield: 304 mg (64%); mp 237–238 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
HRMS (APCI): m/z [M + H]+ calcd for C27H21FNO2S: 442.1272;
found: 442.1269.
FTIR (neat): 3084.2, 2955.0, 2922.2, 2868.2, 1585.5, 1483.3,
1394.5, 1340.5, 1157.3, 1093.6, 1012.6, 821.7, 667.4 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.81–7.84 (d, J = 7.8 Hz, 1 H,
ArH), 7.75–7.80 (m, 3 H, ArH), 7.55–7.59 (m, 3 H, ArH), 7.39–7.42
(t, J = 6.6 Hz, 3 H, ArH), 7.32–7.35 (d, J = 7.8 Hz, 2 H, ArH), 4.87
(s, 2 H, NCH2), 4.76 (s, 2 H, NCH2), 2.39 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 163.3, 143.9, 139.4, 133.7,
133.4, 132.9, 130.7, 130.6, 130.0, 129.9, 128.9, 127.7, 121.8, 120.9,
117.2, 116.8, 109.6, 109.3, 98.3, 84.4, 53.7, 53.5, 21.5.
6-Fluoro-4-(4-tolylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2h)
White solid; yield: 355 mg (78%); mp 196–197 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
FTIR (neat): 3063.0, 3028.2, 2947.2, 2916.4, 2852.7, 2360.9,
2331.9, 1597.1, 1504.5, 1444.7, 1404.2, 1346.3, 1238.3, 1074.4,
1014.6, 968.3, 866.1, 790.8, 667.4 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.92–7.95 (d, J = 7.8 Hz, 1 H,
ArH), 7.75–7.81 (m, 3 H, ArH), 7.52–7.56 (t, J = 8.1 Hz, 3 H, ArH),
7.29–7.31 (t, J = 8.1 Hz, 3 H, ArH), 7.23–7.25 (d, J = 8.1 Hz, 2 H,
ArH), 4.87 (s, 2 H, NCH2), 4.76 (s, 2 H, NCH2), 2.42 (s, 3 H,
ArCH3), 2.39 (s, 3 H, ArCH3).
HRMS (APCI): m/z [M + H]+ calcd for C27H20ClFNO2S: 476.0882;
found: 476.0870.
6-Fluoro-4-[(4-methoxyphenyl)ethynyl]-2-tosyl-2,3-dihydro-
1H-benzo[f]isoindole (2l)
White solid; yield: 245 mg (52%); mp 187–188 °C; Rf = 0.40 (PE–
EtOAc, 6:1).
13C NMR (75.5 MHz, CDCl3): δ = 163.2, 143.9, 139.4, 139.1,
133.6, 133.3, 131.7, 130.5, 130.0, 129.9, 129.3, 127.7, 121.3, 119.4,
117.0, 116.7, 109.7, 109.4, 99.7, 83.0, 53.7, 53.6, 21.7, 21.5.
HRMS (APCI): m/z [M + H]+ calcd for C28H23FNO2S: 456.1428;
found: 456.1424.
Crystal structure:13 C28H22FNO2S, M = 455.53, monoclinic, space
group C2/c, a = 20.825(6), b = 7.511(2), c = 29.279(9) Å,
U = 4554(2) Å3, T = 293 K, Z = 8; 5259 reflections measured,
18655 unique (Rint = 0.0667), which were used in all calculations.
The final wR(F2) was 0.1575 (all data).
FTIR (neat): 3049.5, 2955.0, 2924.1, 1606.7, 1512.2, 1344.4,
1290.4, 1250.0, 1161.2, 1097.5, 1026.1, 831.3, 810.1, 706.0, 790.8,
706.0, 673.2 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.91–7.94 (d, J = 9.9 Hz, 1 H,
ArH), 7.74–7.84 (m, 3 H, ArH), 7.55–7.59 (d, J = 10.5 Hz, 3 H,
ArH), 7.31–7.34 (d, J = 7.5 Hz, 3 H, ArH), 6.94–6.97 (d, J = 8.4 Hz,
2 H, ArH), 4.86 (s, 2 H, NCH2), 4.75 (s, 2 H, NCH2), 3.88 (s, 3 H,
OCH3), 2.39 (s, 3 H, ArCH3).
4-[(4-Ethylphenyl)ethynyl]-6-fluoro-2-tosyl-2,3-dihydro-1H-
benzo[f]isoindole (2i)
White solid; yield: 385 mg (82%); mp 188–189 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
13C NMR (75.5 MHz, CDCl3): δ = 163.1, 159.7, 143.9, 138.9,
133.6, 133.4, 133.3, 130.6, 130.4, 129.9, 127.7, 121.1, 117.0, 116.7,
114.5, 114.2, 109.7, 109.5, 99.7, 82.5, 55.4, 53.7, 53.6, 21.5.
HRMS (APCI): m/z [M + H]+ calcd for C28H23FNO3S: 472.1377;
found: 472.1378.
FTIR (neat): 3030.2, 2964.6, 2924.1, 2875.9, 1597.1, 1508.3,
1452.4, 1400.3, 1348.2, 1161.2, 1097.5, 1062.8, 868.0, 815.9,
788.9, 669.3 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.92–7.95 (d, J = 10.5 Hz, 1 H,
ArH), 7.74–7.83 (m, 3 H, ArH), 7.55–7.56 (d, J = 5.7 Hz, 3 H,
ArH), 7.25–7.33 (m, 5 H, ArH), 4.87 (s, 2 H, NCH2), 4.76 (s, 2 H,
NCH2), 2.68–2.75 (m, 2 H, ArCH2CH3), 2.39 (s, 3 H, ArCH3), 1.26–
1.30 (t, J = 7.5 Hz, 3 H, ArCH2CH3).
13C NMR (75.5 MHz, CDCl3): δ = 163.1, 145.7, 143.9, 139.1,
133.6, 133.4, 131.8, 130.6, 130.5, 129.9, 128.2, 127.7, 121.3, 119.6,
117.0, 116.7, 109.7, 109.4, 100.0, 83.0, 53.7, 53.6, 29.0, 21.5, 15.4.
HRMS (APCI): m/z [M + H]+ calcd for C29H25FNO2S: 470.1585;
found: 470.1575.
8-Methyl-4-(phenylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2m)
White solid; yield: 332 mg (76%); mp 201–202 °C; Rf = 0.49 (PE–
EtOAc, 6:1).
FTIR (neat): 3064.9, 3024.4, 2947.2, 2920.2, 2846.9, 1599.0,
1491.0, 1442.8, 1381.0, 1342.5, 1155.4, 1101.4, 1070.5, 883.4,
798.5, 748.4, 669.3 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.21–8.24 (d, J = 7.2 Hz, 1 H,
ArH), 7.76–7.85 (t, J = 7.2 Hz, 3 H, ArH), 7.64 (s, 2 H, ArH), 7.42
(s, 4 H, ArH), 7.32–7.34 (d, J = 6.6 Hz, 3 H, ArH), 4.90 (s, 2 H,
NCH2), 4.81 (s, 2 H, NCH2), 2.65 (s, 3 H, ArCH3), 2.39 (s, 3 H,
ArCH3).
6-Fluoro-4-[(4-fluorophenyl)ethynyl]-2-tosyl-2,3-dihydro-1H-
benzo[f]isoindole (2j)
White solid; yield: 303 mg (66%); mp 217–219 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
13C NMR (75.5 MHz, CDCl3): δ = 143.8, 137.8, 134.5, 133.9,
133.5, 132.9, 132.2, 131.7, 129.9, 128.9, 128.5, 127.7, 127.4, 126.5,
124.1, 122.8, 117.9, 115.6, 99.1, 84.6, 54.0, 53.8, 21.5, 19.7.
HRMS (APCI): m/z [M + H]+ calcd for C28H24NO2S: 438.1522;
found: 438.1518.
FTIR (neat): 3064.9, 3049.5, 2945.3, 2922.2, 2856.6, 2378.2,
2308.8, 1599.0, 1504.5, 1446.6, 1402.3, 1340.5, 1321.2, 1155.4,
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1547–1554

1552
L. Li et al.
PAPER
8-Methyl-4-(4-tolylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2n)
White solid; yield: 347 mg (77%); mp 227–228 °C; Rf = 0.49 (PE–
EtOAc, 6:1).
FTIR (neat): 3059.1, 3032.1, 2966.5, 2818.3, 2845.0, 1599.0,
1489.1, 1460.1, 1396.5, 1346.3, 1159.2, 1099.4, 1012.6, 827.5,
802.4, 736.8, 706.0, 669.3 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.17–8.20 (d, J = 8.1 Hz, 1 H,
ArH), 7.82–7.84 (d, J = 7.2 Hz, 2 H, ArH), 7.77 (s, 1 H, ArH), 7.55–
7.57 (d, J = 6.9 Hz, 2 H, ArH), 7.38–7.44 (t, J = 7.8 Hz, 2 H, ArH),
7.32–7.34 (t, J = 7.2 Hz, 4 H, ArH), 4.89 (s, 2 H, NCH2), 4.81 (s, 2
H, NCH2), 2.65 (s, 3 H, ArCH3), 2.39 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.8, 138.0, 135.0, 134.6,
133.9, 133.6, 132.9, 132.8, 132.2, 129.9, 128.9, 127.7, 127.4, 126.6,
124.0, 121.3, 118.2, 115.2, 97.9, 85.5, 54.0, 53.8, 21.5, 19.7.
HRMS (APCI): m/z [M + H]+ calcd for C28H23ClNO2S: 472.1133;
found: 472.1127.
FTIR (neat): 3055.2, 2949.2, 2920.2, 2843.1, 1597.1, 1510.3,
1458.2, 1350.2, 1165.0, 1095.6, 814.0, 750.3, 706.0, 798.5, 663.5
cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.22–8.24 (d, J = 7.8 Hz, 1 H,
ArH), 7.82–7.84 (d, J = 8.1 Hz, 2 H, ArH), 7.75 (s, 1 H, ArH), 8.52–
7.55 (d, J = 8.1 Hz, 2 H, ArH), 7.40–7.43 (d, J = 7.8 Hz, 1 H, ArH),
7.31–7.33 (d, J = 7.8 Hz, 3 H, ArH), 7.22–7.24 (d, J = 8.4 Hz, 2 H,
ArH), 4.90 (s, 2 H, NCH2), 4.81 (s, 2 H, NCH2), 2.65 (s, 3 H,
ArCH3), 2.42 (s, 3 H, ArCH3), 2.39 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.8, 139.1, 137.7, 134.4,
133.9, 133.5, 132.8, 132.2, 131.6, 129.9, 129.3, 127.7, 127.3, 126.4,
124.2, 119.7, 117.7, 115.5, 99.3, 84.0, 54.0, 53.8, 21.6, 21.5, 19.7.
HRMS (APCI): m/z [M + H]+ calcd for C29H26NO2S: 452.1679;
found: 452.1681.
4-[(4-Methoxyphenyl)ethynyl]-8-methyl-2-tosyl-2,3-dihydro-
1H-benzo[f]isoindole (2r)
White solid; yield: 290 mg (62%); mp 211–213 °C; Rf = 0.43 (PE–
EtOAc, 6:1).
FTIR (neat): 3057.2, 3036.0, 2955.0, 2918.3, 2845.0, 1604.8,
1514.2, 1454.3, 1342.5, 1290.4, 1155.4, 1101.4, 1028.1, 839.0,
802.4, 752.2, 706.0, 663.5 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.17–8.22 (d, J = 15.3 Hz, 1 H,
ArH), 7.81–7.84 (d, J = 8.4 Hz, 2 H, ArH), 7.72 (s, 1 H, ArH), 7.55–
7.58 (t, J = 6.9 Hz, 2 H, ArH), 7.40–7.42 (d, J = 8.7 Hz, 2 H, ArH),
7.30–7.33 (d, J = 8.1 Hz, 2 H, ArH), 6.92–6.95 (d, J = 8.7 Hz, 2 H,
ArH), 4.89 (s, 2 H, NCH2), 4.80 (s, 2 H, NCH2), 3.87 (s, 3 H,
OCH3), 2.64 (s, 3 H, ArCH3), 2.38 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 160.1, 143.8, 137.5, 134.4,
133.9, 133.8, 133.2, 132.8, 132.3, 129.9, 127.7, 127.3, 126.4, 124.2,
117.5, 116.0, 115.0, 114.2, 99.2, 83.4, 55.4, 54.0, 53.8, 21.5, 19.6.
HRMS (APCI): m/z [M + H]+ calcd for C29H26NO3S: 468.1628;
found: 468.1626.
4-[(4-Ethylphenyl)ethynyl]-8-methyl-2-tosyl-2,3-dihydro-1H-
benzo[f]isoindole (2o)
White solid; yield: 385 mg (81%); mp 186–187 °C; Rf = 0.49 (PE–
EtOAc, 6:1).
FTIR (neat): 3053.3, 3026.3, 2964.6, 2924.11, 2845.0, 1595.1,
1510.3, 1454.3, 1344.4, 1197.5, 1068.6, 1016.5, 835.2, 800.5,
740.7, 661.6 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.20–8.24 (d, J = 8.1 Hz, 1 H,
ArH), 7.82–7.87 (t, J = 7.5 Hz, 2 H, ArH), 7.74 (s, 1 H, ArH), 7.55–
7.57 (d, J = 7.2 Hz, 1 H, ArH), 7.40–7.45 (t, J = 8.1 Hz, 2 H, ArH),
7.31–7.33 (d, J = 6.9 Hz, 3 H, ArH), 7.27 (s, 2 H, ArH), 4.89 (s, 2
H, NCH2), 4.81 (s, 2 H, NCH2), 2.65–2.75 (m, 2 H, ArCH2CH3),
2.65 (s, 3 H, ArCH3), 2.39 (s, 3 H, ArCH3), 1.26–1.30 (t, J = 6.9 Hz,
3 H, ArCH2CH3).
13C NMR (75.5 MHz, CDCl3): δ = 145.5, 143.8, 137.7, 134.4,
133.9, 133.5, 132.9, 132.2, 131.8, 129.9, 128.1, 127.7, 127.3, 126.4,
124.2, 120.0, 117.7, 115.8, 99.4, 84.0, 54.0, 53.8, 29.0, 21.5, 19.7,
15.5.
6-Chloro-4-(phenylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2s)
White solid; yield: 311 mg (68%); mp 235–237 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
HRMS (APCI): m/z [M + H]+ calcd for C30H28NO2S: 466.1835;
found: 466.1839.
FTIR (neat): 3059.1, 3024.4, 2945.3, 2924.1, 2854.7, 1599.0,
1491.0, 1465.9, 1340.5, 1159.2, 1101.4, 1076.3, 1018.4, 895.0,
866.0, 808.2, 760.0, 665.4 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.27–8.28 (d, J = 1.5 Hz, 1 H,
ArH), 7.80–7.83 (d, J = 8.4 Hz, 2 H, ArH), 7.62–7.72 (m, 3 H,
ArH), 7.55 (s, 1 H, ArH), 7.40–7.44 (m, 4 H, ArH), 7.31–7.34 (d,
J = 7.8 Hz, 2 H, ArH), 4.86 (s, 2 H, NCH2), 4.75 (s, 2 H, NCH2),
2.38 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.9, 139.4, 134.6, 133.5,
133.4, 133.0, 131.8, 131.3, 129.9, 129.7, 129.1, 128.6, 127.7, 127.5,
124.8, 122.6, 121.4, 114.6, 99.8, 83.5, 53.7, 53.6, 21.5.
HRMS (APCI): m/z [M + H]+ calcd for C27H21ClNO2S: 458.0976;
found: 458.0975.
4-[(4-Fluorophenyl)ethynyl]-8-methyl-2-tosyl-2,3-dihydro-1H-
benzo[f]isoindole (2p)
White solid; yield: 314 mg (69%); mp 203–204 °C; Rf = 0.49 (PE–
EtOAc, 6:1).
FTIR (neat): 3055.2, 2941.4, 2852.7, 1599.0, 1508.3, 1452.4,
1344.4, 1232.5, 1155.4, 1097.5, 1016.5, 835.2, 802.4, 754.2, 706.0,
663.5 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.18–8.21 (d, J = 8.7 Hz, 1 H,
ArH), 7.82–7.84 (d, J = 6.9 Hz, 2 H, ArH), 7.76 (s, 1 H, ArH), 7.60–
7.62 (d, J = 5.4 Hz, 2 H, ArH), 7.41–7.46 (t, J = 8.1 Hz, 2 H, ArH),
7.26–7.34 (t, J = 8.1 Hz, 2 H, ArH), 7.09–7.12 (t, J = 6.9 Hz, 2 H,
ArH), 4.89 (s, 2 H, NCH2), 4.81 (s, 2 H, NCH2), 2.65 (s, 3 H,
ArCH3), 2.39 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 164.5, 143.8, 137.9, 134.5,
133.9, 133.7, 133.6, 132.8, 132.2, 129.9, 127.7, 127.4, 126.5, 124.0,
118.9, 118.0, 116.0, 115.7, 98.0, 84.2, 54.0, 53.8, 21.5, 19.7.
HRMS (APCI): m/z [M + H]+ calcd for C28H23FNO2S: 456.1428;
found: 456.1425.
6-Chloro-4-(4-tolylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2t)
White solid; yield: 334 mg (71%); mp 221–223 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
FTIR (neat): 3026.3, 2945.3, 2920.2, 2862.4, 1599.0, 1508.3,
1465.9, 1344.4, 1307.7, 1159.2, 1099.4, 1076.3, 1018.4, 931.6,
893.0, 866.0, 808.2, 761.9, 706.0, 665.4 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.28 (s, 1 H, ArH), 7.80–7.83 (d,
J = 8.4 Hz, 2 H, ArH), 7.69–7.71 (d, J = 8.4 Hz, 1 H, ArH), 7.52–
7.54 (d, J = 5.1 Hz, 3 H, ArH), 7.40–7.43 (m, 1 H, ArH), 7.31–7.34
(d, J = 7.8 Hz, 2 H, ArH), 7.23–7.26 (d, J = 8.4 Hz, 2 H, ArH), 4.87
(s, 2 H, NCH2), 4.75 (s, 2 H, NCH2), 2.42 (s, 3 H, ArCH3), 2.39 (s,
3 H, ArCH3).
4-[(4-Chlorophenyl)ethynyl]-8-methyl-2-tosyl-2,3-dihydro-1H-
benzo[f]isoindole (2q)
White solid; yield: 330 mg (70%); mp 236–238 °C; Rf = 0.49 (PE–
EtOAc, 6:1).
Synthesis 2014, 46, 1547–1554
© Georg Thieme Verlag Stuttgart · New York

PAPER
Domino Access to Yne-Functionalized Benzoisoindolines
1553
13C NMR (75.5 MHz, CDCl3): δ = 143.9, 139.5, 139.2, 134.6,
133.5, 133.4, 132.9, 131.7, 131.3, 129.9, 129.6, 129.4, 127.7, 127.4,
124.8, 121.2, 119.3, 114.8, 100.0, 83.0, 53.7, 53.7, 21.7, 21.5.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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HRMS (APCI): m/z [M + H]+ calcd for C28H23ClNO2S: 472.1133;
found: 472.1128.
References
(1) (a) Joule, J. A.; Mills, K. Heterocyclic Chemistry, 4th ed.;
Blackwell: Oxford, 2000. (b) Le Bras, J.; Muzart, J. Chem.
Rev. 2011, 111, 1170. (c) Dediu, V. A.; Hueso, L. E.;
Bergenti, I.; Taliani, C. Nature Mater. 2009, 8, 707.
(d) Pozharskii, A. F.; Soldatenkov, A. T.; Katritzky, A. R.
Heterocycles in Life and Society: An Introduction to
Heterocyclic Chemistry, Biochemistry and Applications;
Wiley: Chichester, 1997. (e) Platon, M.; Amardeil, R.;
Djakovitch, L.; Hierso, J.-C. Chem. Soc. Rev. 2012, 41,
3929. (f) Ackermann, L. Pure Appl. Chem. 2010, 82, 1403.
(2) (a) Stuart, D. R.; Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am.
Chem. Soc. 2010, 132, 18326. (b) Ding, Z. H.; Yoshikai, N.
Angew. Chem. Int. Ed. 2012, 51, 4698. (c) Dunetz, J. R.;
Danheiser, R. L. J. Am. Chem. Soc. 2005, 127, 5776.
(d) Yao, B.; Wang, Q.; Zhu, J. P. Angew. Chem. Int. Ed.
2012, 51, 12311.
6-Methyl-4-(4-tolylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2u)
White solid; yield: 379 mg (84%); mp 224–225 °C; Rf = 0.48 (PE–
EtOAc, 6:1).
FTIR (neat): 3028.2, 2951.1, 2920.2, 2858.5, 1599.0, 1510.3,
1452.4, 1342.5, 1099.4, 1064.7, 877.6, 829.4, 669.3 cm–1.
1H NMR (300 MHz, CDCl3): δ = 8.07 (s, 1 H, ArH), 7.81–7.83 (d,
J = 7.5 Hz, 2 H, ArH), 7.65–7.68 (d, J = 8.4 Hz, 1 H, ArH), 7.52–
7.55 (d, J = 9.3 Hz, 3 H, ArH), 7.30–7.33 (d, J = 7.5 Hz, 3 H, ArH),
7.22 (s, 2 H, ArH), 4.87 (s, 2 H, NCH2), 4.75 (s, 2 H, NCH2), 2.54
(s, 3 H, ArCH3), 2.42 (s, 3 H, ArCH3), 2.38 (s, 3 H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.8, 139.1, 138.2, 136.8,
133.5, 133.1, 132.9, 131.7, 131.3, 129.9, 129.3, 128.8, 128.0, 127.7,
124.8, 121.2, 119.8, 114.5, 99.2, 83.6, 53.8, 53.7, 22.0, 21.7, 21.5.
HRMS (APCI): m/z [M + H]+ calcd for C29H26NO2S: 452.1679;
found: 452.1683.
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6-Methoxy-4-(phenylethynyl)-2-tosyl-2,3-dihydro-1H-ben-
zo[f]isoindole (2v)
White solid; yield: 358 mg (79%); mp 193–194 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
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FTIR (neat): 3059.1, 2989.7, 2945.3, 2868.2, 1614.4, 1502.6,
1464.0, 1342.5, 1246.0, 1107.1, 804.3, 758.0, 663.5 cm–1.
1H NMR (300 MHz, CDCl3): δ = 7.81–7.84 (m, 2 H, ArH), 7.61–
7.69 (m, 4 H, ArH), 7.50 (s, 1 H, ArH), 7.41–7.44 (m, 3 H, ArH),
7.31–7.33 (d, J = 7.8 Hz, 2 H, ArH), 7.13–7.16 (m, 1 H, ArH), 4.87
(s, 2 H, NCH2), 4.74 (s, 2 H, NCH2), 3.95 (s, 3 H, OCH3), 2.38 (s, 3
H, ArCH3).
13C NMR (75.5 MHz, CDCl3): δ = 158.6, 143.8, 138.7, 134.2,
133.6, 131.7, 129.9, 129.7, 128.9, 128.6, 128.4, 127.7, 122.9, 121.5,
119.2, 113.6, 108.8, 104.2, 99.1, 84.4, 55.3, 53.9, 53.7, 21.5.
HRMS (APCI): m/z [M + H]+ calcd for C28H24NO3S: 454.1471;
found: 454.1479.
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4-Hex-1-yn-1-yl-2-tosyl-2,3-dihydro-1H-benzo[f]isoindole (2w)
White solid; yield: 326 mg (81%); mp 130–131 °C; Rf = 0.42 (PE–
EtOAc, 6:1).
FTIR (neat): 3057.2, 2953.0, 2929.9, 2858.5, 1595.1, 1465.9,
1346.3, 1159.2, 1095.6, 746.5, 667.4, 594.1 cm–1;
1H NMR (300 MHz, CDCl3): δ = 8.21–8.23 (d, J = 7.8 Hz, 1 H,
ArH), 7.80–7.82 (d, J = 7.8 Hz, 2 H, ArH), 7.72–7.75 (d, J = 7.5 Hz,
1 H, ArH), 7.44–7.51 (t, J = 7.2 Hz, 3 H, ArH), 7.30–7.33 (d, J = 7.8
Hz, 2 H, ArH), 4.78 (s, 2 H, NCH2), 4.74 (s, 2 H, NCH2), 2.56–2.61
(t, J = 6.9 Hz, 2 H, C≡CCH2), 2.38 (s, 3 H, ArCH3), 1.65–1.72 (q,
J = 6.9 Hz, 2 H, C≡CCH2CH2), 1.52–1.59 (q, J = 6.9 Hz, 2 H,
CH2CH3), 0.98–1.03 (t, J = 6.9 Hz, 3 H, CH2CH3).
13C NMR (75.5 MHz, CDCl3): δ = 143.8, 138.0, 133.9, 133.4,
132.9, 129.9, 128.1, 127.7, 126.6, 126.3, 125.8, 120.7, 116.0, 113.9,
100.9, 75.6, 53.8, 53.8, 31.0, 22.2, 21.5, 19.6, 13.8.
HRMS (APCI): m/z [M + H]+ calcd for C25H26NO2S: 404.1684;
found: 404.1681.
Acknowledgment
The authors thank the National Science Foundation of China
(21272005, 21072003) for financial support.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1547–1554

1554
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Synthesis 2014, 46, 1547–1554
© Georg Thieme Verlag Stuttgart · New York