Three-component reaction of 2-alkynylbenzaldehyde, amine, and nucleophile using Lewis acid-surfactant combined catalyst in water

Article abstract of DOI:10.1016/j.tet.2007.11.055

Lewis acid-surfactant combined catalyst (LASC) catalyzed three-component reactions of 2-alkynylbenzaldehyde, amines, and nucleophiles (alkyne, nitromethane, or diethyl phosphate) in water under ultrasonic conditions afforded the corresponding 1,2-dihydroisoquinoline derivatives in good yields.

Full text of DOI:10.1016/j.tet.2007.11.055

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 1378e1382
www.elsevier.com/locate/tet
Three-component reaction of 2-alkynylbenzaldehyde, amine, and
nucleophile using Lewis acid-surfactant combined catalyst in water
Yang Ye a, Qiuping Ding a,c, Jie Wu a,b,
*
a Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032, China
c Analytical Centre for Physics and Chemistry, Jiangxi Normal University, 437 West Beijing Road, Nanchang 330027, China
Received 26 September 2007; received in revised form 14 November 2007; accepted 16 November 2007
Available online 21 November 2007
Abstract
Lewis acid-surfactant combined catalyst (LASC) catalyzed three-component reactions of 2-alkynylbenzaldehyde, amines, and nucleophiles
(alkyne, nitromethane, or diethyl phosphate) in water under ultrasonic conditions afforded the corresponding 1,2-dihydroisoquinoline derivatives
in good yields.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Lewis acid-surfactant combined catalyst; Water; Ultrasonic; 1,2-Dihydroisoquinoline
1. Introduction
in many natural products with remarkable biological activi-
ties.6 The prominence of 1,2-dihydroisoquinoline in natural
products and biologically active molecules has promoted con-
siderable efforts toward their synthesis.7,8 For instance, Yama-
moto and Takemoto described recently the synthesis of
functionalized 1,2-dihydroisoquinoline skeletons through the
direct addition of various carbon pronucleophiles to ortho-
alkynylaryl aldimines catalyzed by Lewis acid.7aec Based on
these results, we conceived that this kind of reaction may be
performed in water via combination of 2-alkynylbenzalde-
hyde, amine, and nucleophile under suitable conditions instead
of ortho-alkynylaryl aldimine. This three-component one-pot
procedure in water will provide a new, rapid, and environmen-
tally benign route to prepare 1,2-dihydroisoquinoline deriva-
tives. Thus, we started to investigate the possibility of this
reaction.
Lewis acid catalysis has received continuous attention in
organic synthesis.1 Recently, ‘Lewis acid-surfactant combined
catalyst (LASC)’, shows high efficiency in various organic
transformations as a new type of catalyst. These reactions are
promoted in water without organic cosolvents.2 Proposed by
Kobayashi,3 this kind of catalyst acts both as a Lewis acid to
activate the substrate molecules and as a surfactant to form
emulsions in water. High efficiency of LASC in reactions, as
well as the environmentally benign processes promoted us to
explore the possibility to develop scaffold construction of
natural product-like compounds.
Availability of practical route for generation of small mole-
cules based natural products is of utmost urgency and impor-
tance in the biomedical research.4 Realizing such a critical
need, we have focused on the development of methodologies
for facile synthesis of natural product-like molecules.5 As
a privileged fragment, 1,2-dihydroisoquinoline is a subunit
2. Results and discussion
Initial studies were performed by treatment of 2-alkynyl-
benzaldehyde 1, aniline 2a, and phenylacetylene 3a in water
in the presence of a catalytic amount of various Lewis
* Corresponding author. Tel.: þ86 2155664619; fax: þ86 2165102412.
E-mail address: jie_wu@fudan.edu.cn (J. Wu).
0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.055

Y. Ye et al. / Tetrahedron 64 (2008) 1378e1382
1379
acid-surfactant combined catalysts (LASC) (10 mol %), and
the results are shown in Table 1. To our delight, we found
that the desired product 4a could be afforded in 39% yield
when AgC12H25SO3 (10 mol %) was utilized as the catalyst
(Table 1, entry 1). However, when other metals were employed
in the reaction, inferior results were observed (Table 1, entries
2e13). For example, only trace amount of product 4a was de-
tected in the presence of Yb(C12H25OSO3)3 (10 mol %) (Table
1, entry 9). Further studies revealed that the yield could be dra-
matically improved under ultrasonic conditions [Table 1, entry
14: 80% yield, AgC12H25SO3 (10 mol %)]. Using AgOTf in-
stead of AgC12H25SO3 afforded 4a in 32% yield (Table 1, en-
try 20). Meanwhile, trace amount of product was detected
when only C12H25SO3Na (10 mol %) was utilized (Table 1,
entry 21). We also found that the reaction proceeded smoothly
to generate the corresponding product 4a in 89% yield in the
presence of combination of C12H25SO3Na (10 mol %) and
CuSO4 (10 mol %) (Table 1, entry 17). Similar result (87%
yield) was observed when the amount of catalyst was de-
creased to 5 mol % (Table 1, entry 18). However, prolonged
reaction time was necessary to complete the reaction. Again,
surfactant is crucial for this reaction, since only trace amount
of product 4a was generated when CuSO4 (10 mol %) was em-
ployed without C12H25SO3Na (10 mol %) (Table 1, entry 19).
To demonstrate the generality of this method, we next inves-
tigated the scope of substrates under optimized conditions
[C12H25SO3Na (10 mol %), CuSO4 (10 mol %), ultrasonic],
and the results are summarized in Table 2. 2-Alkynylbenzalde-
hyde 1 reacted with various aromatic amines and phenylacetyl-
ene to afford the corresponding products 4aef in good to
excellent yields, catalyzed by C12H25SO3Na/CuSO4 under
ultrasonic conditions (Table 2, entries 1e6). Aromatic amines
with electron-donating or electron-withdrawing group attached
to the aromatic ring were all good partners in this transforma-
tion. For example, p-toluidine 2c reacted with 2-alkynylbenzal-
dehyde 1 and phenylacetylene 3a leading to the corresponding
product 4c in 77% yield (Table 2, entry 3), and almost quanti-
tative yield (98%) of product 4e was obtained when 4-chloro-
benzeneamine 2e was utilized in the reaction (Table 2, entry 5).
However, aliphatic amines were not suitable in this reaction.
Table 2
Reaction of 2-alkynylbenzaldehyde 1, amine 2, and alkyne 3 in water cata-
lyzed by Lewis acid-surfactant combined catalyst (LASC)
R2
CuSO4 (10 mol%)
CHO
C12H25SO3Na (10 mol%)
R1
Ph
+ R1 NH2
R2
+
N
H2O, ultrasonic
Ph
3
1
2
4
Entry
1
Amine 2
Alkyne 3
Product Yield (%)a
NH2
4a
4b
4c
4d
4e
4f
89
2a
NH2
NH2
2
63
Table 1
Conditions screening for Lewis acid-catalyzed reaction of 2-alkynylbenzalde-
hyde 1, aniline 2a, and phenylacetylene 3a in water
2b
MeO
Me
F
Ph
3
77
2c
CHO
Cat.
H2O
NH2
NH2
+
+
Ph
Ph
N
4
84
Ph
4a
3a
2a
1
2d
NH2
3a
Yield (%)a
5
98
Entry Conditions
Cl
2e
NH2
2f
1
Ag(C12H25SO3) (10 mol %), 50e60 ꢀC
Y(C12H25SO3)3 (10 mol %), 70e80 ꢀC
Fe(C12H25SO3)3 (10 mol %), 70e80 ꢀC
Dy(C12H25SO3)3 (10 mol %), 70e80 ꢀC
Gd(C12H25SO3)3 (10 mol %), 70e80 ꢀC
Sm(C12H25SO3)3 (10 mol %), 70e80 ꢀC
Yb(C12H25SO3)3 (10 mol %), 70e80 ꢀC
Gd(C12H25OSO3)3 (10 mol %), 70e80 ꢀC
Yb(C12H25OSO3)3 (10 mol %), 70e80 ꢀC
Y(C12H25OSO3)3 (10 mol %), 70e80 ꢀC
Fe(C12H25OSO3)3 (10 mol %), 70e80 ꢀC
Dy(C12H25OSO3)3 (10 mol %), 70e80 ꢀC
Sm(C12H25OSO3)3 (10 mol %), 70e80 ꢀC
AgC12H25SO3 (10 mol %), ultrasonic
39
17
2
O2N
6
88
3
16
30
4
5
7
NH2
2g
6
7
12
7
4g
4h
4i
Trace
86
7
8
Trace
Trace
Trace
Trace
Trace
Trace
80
NH2
2a
9
8
10
11
12
13
14
15
16
17
18
19
20
21
a
3b
NH2
NH2
9
66
n
2a
C5H11
3c
C
12H25SO3Na (10 mol %)/AgOTf (10 mol %), ultrasonic 65
C12H25SO3Na (10 mol %)/CuI (10 mol %), ultrasonic 76
C12H25SO3Na (10 mol %)/CuSO4 (10 mol %), ultrasonic 89
10
4j
37
3d
2a
C12H25SO3Na (5 mol %)/CuSO4 (5 mol %), ultrasonic
CuSO4 (10 mol %), ultrasonic
AgOTf (10 mol %), ultrasonic
87
NH2
2b
Trace
32
Trace
11
4k
36
3d
MeO
C12H25SO3Na (10 mol %), ultrasonic
a
Isolated yield based on 2-alkynylbenzaldehyde 1.
Isolated yield based on 2-alkynylbenzaldehyde 1.

1380
Y. Ye et al. / Tetrahedron 64 (2008) 1378e1382
Only trace amount of product 4g was obtained when benzyl
amine 2g was employed in the reaction with 2-alkynylbenzal-
dehyde 1 and phenylacetylene 3a (Table 2, entry 7). Other
substituted phenylacetylenes 3b and 3c were also effective in
this kind of reaction and good yields of products 4h and 4i
were observed (Table 2, entries 8 and 9). However, only low
yield of product 4j or 4k was obtained when 1-hexyne 3d
was used in the reaction (Table 2, entries 10 and 11).
Other nucleophiles instead of acetylene, such as nitrometh-
ane and diethylphosphite, were also tested in this kind of
transformation. As outlined in Scheme 1, reaction of 2-alky-
nylbenzaldehyde 1, aniline 2a, and nitromethane 5 in water
catalyzed by C12H25SO3Na/CuSO4 (10 mol %) under ultra-
sonic conditions afforded the desired product 6 in 49% yield
(Scheme 1, Eq. 1). When diethylphosphite 7 was employed
under the same conditions, the corresponding product 8 was
generated in 65% yield (Scheme 1, Eq. 2). Silver catalyst was
also effective in this reaction and 79% yield of compound 8
was obtained (Scheme 1, Eq. 3).
indicator (254 nm). Solvents and other commercial reagents
were used as received. 2-Alkynylbenzaldehyde 1 was synthe-
sized via Sonogashira coupling according to the literature
report.8e
4.2. General procedure for synthesis of compound 4
A mixture of 2-alkynylbenzaldehyde 1 (0.5 mmol), amine 2
(0.5 mmol, 1.0 equiv), alkyne 3 (0.6 mmol, 1.2 equiv), CuSO4
(10 mol %), and C12H25SO3Na (5 mol %) in water (3.0 mL)
was stirred under ultrasonic conditions. After completion of
the reaction as indicated by TLC, the reaction mixture was fil-
tered and the filtrate was extracted with EtOAc (2ꢁ10 mL).
Evaporation of the organic solvent followed by purification
of the residue on silica gel afforded pure 1,2-dihydroisoquino-
lin-1-ylphosphonate 4.
4.2.1. 2,3-Diphenyl-1-(2-phenylethynyl)-1,2-
dihydroisoquinoline (4a)7a
1
Yield 89%. H NMR (400 MHz, CDCl3) d 6.03 (s, 1H),
CH2NO2
CHO
CuSO4 (10 mol%)
C12H25SO3Na (10 mol%)
NH2
2a
Ph
6.48 (s, 1H), 6.83 (t, J¼7.3 Hz, 1H), 6.98 (d, J¼7.4 Hz, 2H),
7.09 (t, J¼7.4 Hz, 2H), 7.17e7.26 (m, 10H), 7.33e7.35 (m,
2H), 7.50 (d, J¼7.8 Hz, 2H); m/z: 383 (Mþ).
N
+
(1)
H2O, ultrasonic
49% yield
CH3NO2
Ph
5
Ph
1
6
OEt
OEt
CHO
O
O
4.2.2. 2-(4-Methoxyphenyl)-3-phenyl-1-(2-phenylethynyl)-
CuSO4 (10 mol%)
NH2
2a
P
C12H25SO3Na (10 mol%)
+
1,2-dihydroisoquinoline (4b)
Ph
(2)
(3)
N
1
Yield 63%. H NMR (400 MHz, CDCl3) d 3.65 (s, 3H),
H2O, ultrasonic
65% yield
HP(O)(OEt)2
Ph
Ph
5.92 (s, 1H), 6.44 (s, 1H), 6.64 (d, J¼9.2 Hz, 2H), 6.95 (d,
J¼8.7 Hz, 2H), 7.16e7.26 (m, 10H), 7.34e7.36 (m, 2H),
7.50 (d, J¼8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 55.3, 56.7, 84.3, 88.9, 109.7, 113.8, 123.0, 123.8, 124.3,
125.3, 126.4, 127.7, 127.8, 127.9, 128.0, 128.1, 128.8, 131.8,
132.1, 137.8, 139.6, 141.6, 155.0; m/z: 413 (Mþ). HRMS calcd
for C30H23NO: 413.1780, found: 413.1792.
1
7
8
OEt
N
CHO
NH2
2a
OEt
Ph
P
Ag(C12H25SO3) (10 mol%)
H2O, ultrasonic
+
HP(O)(OEt)2
Ph
79% yield
Ph
1
7
8
Scheme 1.
4.2.3. 3-Phenyl-1-(2-phenylethynyl)-2-p-tolyl-1,2-
dihydroisoquinoline (4c)
3. Conclusion
1
Yield 77%. H NMR (400 MHz, CDCl3) d 2.17 (s, 1H),
In summary, we have described that Lewis acid-surfactant
combined catalyst shows efficiency in the three-component
reaction of 2-alkynylbenzaldehydes, amines, and nucleophiles
in water. This method offers a mild and efficient route for the
synthesis of 1,2-dihydroisoquinoline derivatives. The advan-
tages of this method include good yields, environmentally
benign, and experimentally operational ease.
5.99 (s, 1H), 6.46 (s, 1H), 6.90 (s, 4H), 7.16e7.26 (m, 10H),
7.34e7.36 (m, 2H), 7.50 (dd, J¼1.8, 8.3 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d 20.6, 56.3, 84.2, 88.8, 110.5, 122.0,
123.0, 124.5, 125.3, 126.4, 127.7, 127.9, 128.1, 128.2, 129.1,
129.2, 131.4, 131.8, 132.0, 137.9, 141.2, 143.5; m/z: 397
(Mþ). HRMS calcd for C30H23N: 397.1830, found: 397.1845.
4. Experimental section
4.2.4. 2-(4-Fluorophenyl)-3-phenyl-1-(2-phenylethynyl)-
1,2-dihydroisoquinoline (4d)
1
Yield 84%. H NMR (400 MHz, CDCl3) d 5.93 (s, 1H),
4.1. General
6.48 (s, 1H), 6.79 (t, J¼8.7 Hz, 2H), 6.93e6.96 (m, 2H),
7.18e7.26 (m, 10H), 7.34e7.36 (m, 2H), 7.48 (dd, J¼1.8,
8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3) d 56.4, 84.5, 88.4,
110.7, 115.2 (2JCF¼21.9 Hz), 122.8, 123.5, 123.6, 124.6,
125.3, 126.7, 127.9, 128.0, 128.1, 128.2, 128.3, 129.1, 131.8,
137.4, 141.1, 142.1, 158.2 (1JCF¼241.2 Hz); m/z: 401 (Mþ).
HRMS calcd for C29H20FN: 401.1580, found: 401.1598.
All reactions were performed in test tubes under nitrogen
atmosphere. Flash column chromatography was performed
˚
using silica gel (60 A pore size, 32e63 mm, standard grade,
Sorbent Technologies). Analytical thin layer chromatography
was performed using glass plates pre-coated with 0.25 mm
230e400 mesh silica gel impregnated with a fluorescent

Y. Ye et al. / Tetrahedron 64 (2008) 1378e1382
1381
4.2.5. 2-(4-Chlorophenyl)-3-phenyl-1-(2-phenylethynyl)-
4.2.10. 1-(Hex-1-ynyl)-2-(4-methoxyphenyl)-3-phenyl-
1,2-dihydroisoquinoline (4e)
1,2-dihydroisoquinoline (4k)
Yield 36%. 1H NMR (400 MHz, CDCl3) d 0.83 (t,
J¼6.8 Hz, 3H), 1.26e1.43 (m, 4H), 2.15 (t, J¼7.8 Hz, 2H),
3.66 (s, 3H), 5.68 (s, 1H), 6.38 (s, 1H), 6.63 (d, J¼8.8 Hz,
2H), 6.89 (d, J¼8.8 Hz, 2H), 7.09 (d, J¼7.8 Hz, 2H),
7.13e7.25 (m, 6H), 7.46 (dd, J¼2.0, 8.5 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d 18.6, 21.8, 30.8, 55.3, 56.2, 79.7, 85.0,
109.4, 113.7, 123.6, 124.2, 125.0, 126.2, 127.6, 127.9, 128.1,
129.6, 131.9, 137.9, 139.7, 141.5, 145.8, 154.8; m/z: 393
(Mþ). HRMS calcd for C28H27NO: 393.2093, found: 393.2098.
1
Yield 98%. H NMR (400 MHz, CDCl3) d 5.95 (s, 1H),
6.50 (s, 1H), 6.90 (d, J¼8.8 Hz, 2H), 7.05 (d, J¼8.8 Hz,
2H), 7.19e7.27 (m, 10H), 7.33e7.35 (m, 2H), 7.48 (dd, J¼
1.8, 8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3) d 56.0, 84.6,
88.1, 111.5, 122.7, 122.9, 124.7, 125.3, 126.8, 127.0, 127.8,
128.0, 128.1, 128.2, 128.4, 128.5, 129.4, 131.6, 131.8, 137.5,
140.7, 144.4; m/z: 417 (Mþ). HRMS calcd for C29H20ClN:
417.1284, found: 417.1290.
4.2.6. 2-(3-Nitrophenyl)-3-phenyl-1-(2-phenylethynyl)-
4.2.11. Synthesis of compound 6
1,2-dihydroisoquinoline (4f)
1
Yield 88%. H NMR (400 MHz, CDCl3) d 6.04 (s, 1H),
A mixture of 2-alkynylbenzaldehyde 1 (0.5 mmol), aniline
2a (0.5 mmol, 1.0 equiv), nitromethane 5(0.6 mmol, 1.2 equiv),
CuSO4 (10 mol %), and C12H25SO3Na (5 mol %) in water
(3.0 mL) was stirred under ultrasonic conditions. After com-
pletion of the reaction as indicated by TLC, the reaction
mixture was filtered and the filtrate was extracted with EtOAc
(2ꢁ10 mL). Evaporation of the organic solvent followed by
purification of the residue on silica gel afforded the correspond-
ing 2-(4-methoxyphenyl)-1-(nitromethyl)-3-phenyl-1,2-dihy-
droisoquinoline (6).7a Yield 49%. 1H NMR (400 MHz,
CDCl3) d 4.35 (dd, J¼3.9, 11.7 Hz, 1H), 4.79 (t, J¼11.2 Hz,
1H), 5.74 (dd, J¼3.9, 11.2 Hz, 1H), 6.77 (s, 1H), 6.85e6.91
(m, 3H), 7.05e7.12 (m, 3H), 7.19e7.29 (m, 4H), 7.32 (d,
J¼3.9 Hz, 2H), 7.53 (d, J¼7.8 Hz, 2H).
6.61 (s, 1H), 7.16e7.38 (m, 14H), 7.49 (dd, J¼1.8, 8.3 Hz,
2H), 7.66 (dt, J¼1.8, 7.8 Hz, 1H), 7.89 (t, J¼1.8 Hz, 1H).
13C NMR (100 MHz, CDCl3) d 55.6, 85.1, 87.1, 113.3,
115.4, 116.2, 122.4, 125.1, 125.3, 127.1, 127.3, 127.7, 128.1,
128.2, 128.3, 128.4, 128.5, 128.6, 129.1, 131.3, 131.8, 136.7,
139.7, 146.5, 148.6; m/z: 428 (Mþ). HRMS calcd for
C29H20N2O2: 428.1525, found: 428.1543.
4.2.7. 2,3-Diphenyl-1-(2-p-tolylethynyl)-1,2-
dihydroisoquinoline (4h)
1
Yield 86%. H NMR (400 MHz, CDCl3) d 2.28 (s, 3H),
6.02 (s, 1H), 6.47 (s, 1H), 6.83 (t, J¼7.4 Hz, 1H), 6.98e7.03
(m, 4H), 7.09 (t, J¼7.4 Hz, 2H), 7.17e7.27 (m, 9H), 7.49
(dd, J¼1.9, 8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 21.4, 56.0, 84.4, 87.8, 111.0, 119.8, 121.8, 121.9, 124.5,
125.3, 126.5, 127.7, 127.8, 127.9, 128.2, 128.5, 128.8, 129.6,
131.7, 131.8, 137.8, 138.2, 140.9, 145.8; m/z: 397 (Mþ). HRMS
calcd for C30H23N: 397.1830, found: 397.1852.
4.2.12. Synthesis of compound 8
A mixture of 2-alkynylbenzaldehyde 1 (0.5 mmol), aniline
2a (0.5 mmol, 1.0 equiv), diethylphosphite 7 (0.6 mmol,
1.2 equiv), CuSO4 (10 mol %), and C12H25SO3Na (5 mol %)
in water (3.0 mL) was stirred under ultrasonic conditions. Af-
ter completion of the reaction as indicated by TLC, the reac-
tion mixture was filtered and the filtrate was extracted with
EtOAc (2ꢁ10 mL). Evaporation of the organic solvent fol-
lowed by purification of the residue on silica gel afforded
the diethyl 2,3-diphenyl-1,2-dihydroisoquinolin-1-ylphospho-
nate (8)5d as yellow liquid in 65% yield. 1H NMR
(400 MHz, CDCl3) d 1.20e1.25 (m 6H), 3.90e4.10 (m, 4H),
5.45 (d, J¼18.6 Hz, 1H), 6.50 (s, 1H), 6.85e6.87 (m, 1H),
7.07e7.25 (m, 11H), 7.58 (d, J¼6.8 Hz, 2H). 13C NMR
(100 MHz, CDCl3) d 16.4, 62.5, 62.7, 64.2, 112.2, 122.3,
122.6, 124.3, 125.6, 126.5, 127.2, 127.6, 127.9, 128.2, 128.5,
133.0, 137.3, 142.0, 147.6. 31P NMR (161 MHz, CDCl3)
d 21.33. IR (cmꢂ1) nmax 1025 (PeO), 1052 (PeO), 1251
(P]O). MS (ESI) m/z 420.20 (Mþþ1). HRMS calcd for
C25H26NO3P: 419.1650, found: 419.1654.
4.2.8. 1-(2-(4-Pentylphenyl)ethynyl)-2,3-diphenyl-
1,2-dihydroisoquinoline (4i)
Yield 66%. 1H NMR (400 MHz, CDCl3) d 0.85 (t,
J¼6.9 Hz, 3H), 1.22e1.30 (m, 6H), 2.53 (t, J¼7.8 Hz, 2H),
6.02 (s, 1H), 6.47 (s, 1H), 6.83 (t, J¼6.8 Hz, 1H), 6.98 (d,
J¼7.8 Hz, 2H), 7.03 (d, J¼7.8 Hz, 2H), 7.05e7.29 (m,
11H), 7.49 (d, J¼6.8 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 14.1, 22.5, 31.0, 31.5, 35.8, 56.1, 87.9, 111.1, 121.9,
122.0, 124.7, 125.4, 126.7, 127.8, 127.9, 128.3, 128.6,
131.8, 138.1, 140.8, 137.8, 138.2, 140.9 146.1; m/z: 453
(Mþ). HRMS calcd for C34H31N: 453.2457, found: 453.2468.
4.2.9. 1-(Hex-1-ynyl)-2,3-diphenyl-1,2-dihydro-
isoquinoline (4j)
Yield 37%. 1H NMR (400 MHz, CDCl3) d 0.83 (t,
J¼7.4 Hz, 3H), 1.24e1.43 (m, 4H), 2.15 (t, J¼7.8 Hz, 2H),
5.78 (s, 1H), 6.43 (s, 1H), 6.82 (t, J¼7.4 Hz, 1H), 6.93 (d,
J¼7.3 Hz, 2H), 7.07 (d, J¼7.3 Hz, 2H), 7.09e7.25 (m, 8H),
7.45 (dd, J¼1.5, 8.3 Hz, 2H). 13C NMR (100 MHz, CDCl3)
d 18.5, 21.8, 29.7, 30.8, 55.5, 79.5, 85.0, 110.7, 121.6,
124.5, 125.0, 126.4, 127.6, 127.7, 127.8, 128.1, 128.4, 130.3,
131.6, 137.8, 140.3, 145.9; m/z: 363 (Mþ). HRMS calcd for
C27H25N: 363.1987, found: 363.1956.
Acknowledgements
We thank Dr. Renhua Fan for his invaluable advice during
the course of this research. Financial support from National
Natural Science Foundation of China (20772018), Program
for New Century Excellent Talents in University (NCET-
07-0208), and Shanghai Pujiang Program is gratefully
acknowledged.

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Y. Ye et al. / Tetrahedron 64 (2008) 1378e1382
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