An efficient route to 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonates via CuI-catalyzed three-component reactions

Article abstract of DOI:10.1016/j.tet.2007.09.044

Copper(I) iodide catalyzed three-component reactions of 2-alkynyl benzaldehyde, amine, and diethyl phosphite provide a facile and efficient route to 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonate. Palladium(II) chloride gives the similar results. An isoquinolinium intermediate may be involved in the reaction process.

Full text of DOI:10.1016/j.tet.2007.09.044

Tetrahedron 63 (2007) 12166–12171
An efficient route to 2,3-disubstituted-1,2-dihydroisoquinolin-1-
ylphosphonates via CuI-catalyzed three-component reactions
a,c
Qiuping Ding, Bing Wang and Jie Wu
a,*
a,b,*
a
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
54 Fenglin Road, Shanghai 200032, China
b
3
c
Analytical Centre for Physics and Chemistry, Jiangxi Normal University, 437 West Beijing Road, Nanchang 330027, China
Received 2 August 2007; revised 18 September 2007; accepted 21 September 2007
Available online 26 September 2007
Abstract—Copper(I) iodide catalyzed three-component reactions of 2-alkynyl benzaldehyde, amine, and diethyl phosphite provide a facile
and efficient route to 2,3-disubstituted-1,2-dihydroisoquinolin-1-ylphosphonate. Palladium(II) chloride gives the similar results. An isoqui-
nolinium intermediate may be involved in the reaction process.
Ó 2007 Elsevier Ltd. All rights reserved.
1
. Introduction
Yamamoto and Takemoto described that functionalized 1,2-
dihydroisoquinoline skeletons could be generated through
the direct addition of various carbon pronucleophiles to
A goal of chemical genetics is to find small molecules that
modulate the individual functions of gene products with
high potency and high specificity. Natural products and nat-
ural product-derived compounds provide many of the most
striking examples, particularly, in terms of their specificity.
Efficient methods for preparing natural product-like com-
pounds are in great demand in the field of chemical genet-
1
0a–c
ortho-alkynylaryl aldimines catalyzed by Lewis acid.
Yamamoto also reported that the reaction could be per-
formed in the absence of catalyst when chloroform was uti-
1
1
0d
lized as carbon pronucleophile.
In connection with our
ongoing program for the construction of natural product-
1
2
like compounds, we conceived that we could employ
2-alkynyl benzaldehyde 1 as substrate in the reaction of
amine and diethyl phosphite in the presence of catalytic
Lewis acid, with the hope to generate 1,2-dihydroisoquino-
lin-1-ylphosphonate scaffold (Scheme 1). Indeed, the reac-
tion occurred in the presence of silver triflate as the
1
ics. On the other hand, multicomponent reactions (MCR)
have emerged as a powerful tool for delivering the molecular
diversity needed in the combinatorial approaches for the
preparation of bioactive compounds. However, the range
of easily accessible and functionalized small heterocycles
is rather limited. Thus, the development of new, rapid, and
robust routes toward focused libraries of such heterocycles
is of great importance.
2
1
2c
10b
catalyst. As described by Asao and Yamamoto, ortho-
alkynylaryl aldimines reacted with AgOTf leading to isoqui-
noliniums in good yields. The observation indicated that, in
the presence of silver salt, the triple bond might coordinate to
the silver salt, and subsequently, the nitrogen atom could at-
tack on the triple bond via 6-endo-cyclization to afford an
isoquinolinium intermediate. Based on this result, we con-
ceive that reaction of 2-alkynyl benzaldehyde 1, amine,
and diethyl phosphite catalyzed by other soft Lewis acid
may undergo similar process. The results are disclosed
herein.
Recently, we have described three-component reactions of
aldehydes, amines, and diethyl phosphite catalyzed by
Lewis acid affording the corresponding a-amino phospho-
3
nates in excellent yields. Inspired by these results, we envis-
aged that the resulting a-amino phosphonate could serve as
nucleophile if an electrophile is available in the reaction sys-
tem. It is well-precedented that the transition metal or Lewis
acid catalyzed cyclization of alkynes possessing a nucleo-
phile in proximity to the triple bond is an important process
in organic synthesis, which can construct various heterocy-
2. Results and discussion
4
–11
cles in an efficient and atom-economic way.
Meanwhile,
We tested this idea with 2-alkynyl benzaldehyde 1a,
p-anisidine 2a, and diethyl phosphite 3, which are either
commercially available or can be readily synthesized
*
Corresponding authors. Tel.: +86 2155664619; fax: +86 2165102412
J.W.); e-mail: jie_wu@fudan.edu.cn
(
0
040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.044

Q. Ding et al. / Tetrahedron 63 (2007) 12166–12171
12167
CHO
these salts, CuI is one of the most popular reagents for induc-
ing transformations, which takes advantage of its affinity to
carbon–carbon unsaturated bonds rather than oxygen func-
+
R2 NH2
+
HP(O)(OEt)2
R1
2
3
13
tional groups. Compound 4a could be generated in 83%
ꢀ
1
yield when the reaction was performed at 60 C in dichloro-
EtO
P
EtO
O
ethane and catalyzed by 10 mol % of CuI. Further studies
showed that dichloroethane or toluene was the best solvent.
Decreasing the temperature or the amount of catalyst
retarded the reaction.
EtO
O
N
EtO
P
R2
R1
R2
N
H
Lewis acid
R1
4
[M]
With this promising result in hand, we started to investigate
the three-component reactions of 2-alkynyl benzaldehyde 1
and amine 2 with diethyl phosphite 3 catalyzed by copper(I)
iodide under optimized reaction conditions [CuI (10 mol %),
Scheme 1.
(
Table 1). First, various Lewis acids were screened and the
results are summarized in Table 1. We found that the desired
,2-dihydroisoquinolin-1-ylphosphonate 4a could be ob-
tained when copper(II) triflate or copper(I) iodide was
utilized as the catalyst; while a-amino phosphonate 5a was
obtained when Sc(OTf) , Bi(OTf) , In(OTf) , FeCl , AuCl,
or AuCl was employed as the catalyst in the reaction. It is
3
well-documented that copper salts have mild Lewis acidity
and have been used as catalysts in organic synthesis. Among
ꢀ
dichloroethane, and 60 C]. The results are shown in Table 2.
From Table 2, we found that these conditions were highly ef-
fective for the three-component reactions. For most cases,
1
2
-alkynyl benzaldehydes 1 reacted smoothly with amines 2
and diethyl phosphite 3 leading to 1,2-dihydroisoquinolin-
-ylphosphonates 4 in good to excellent yields. However, re-
3
3
3
3
1
actions of 2-alkynyl benzaldehydes 1, aliphatic amines, and
diethyl phosphite 3 displayed inferior results. For example,
reaction of 1a, aniline 2g, and diethyl phosphite 3 gave
the corresponding product 4g in 91% yield (Table 2, entry
7
), while 61% yield of 4i or 27% yield of 4j was obtained,
Table 1. Reaction of 2-alkynyl benzaldehyde 1a and p-anisidine with
diethyl phosphite catalyzed by various Lewis acids
a
respectively, when benzyl amine or n-hexylamine was
employed in this reaction (Table 2, entries 9 and 10). And
also, a range of different aniline derivatives bearing elec-
tron-donating or electron-withdrawing groups are tolerated.
Interestingly, this three-component reaction could also be
CHO
+
NH2
OCH3 + HP(O)(OEt)2
Ph
1a
2a
3
EtO
EtO
EtO P
Lewis acid
cat.)
O
OCH3
O
OCH3
Table 2. Reaction of 2-alkynyl benzaldehyde 1 and amine 2 with diethyl
phosphate 3 catalyzed by CuI (10 mol %)
EtO
P
a
(
+
ClCH2CH2Cl
N
N
H
EtO
O
CHO
EtO
P
Ph
CuI (10 mol%)
ClCH2CH2Cl
R2 NH2
R2
R1
+
+
HP(O)(OEt)2
Ph
Yield (%)
4
a
5a
N
R1
ꢀ
b
Entry
Lewis acid
mol %)
Solvent
T ( C)
1
2
3
4
(
4
a
5a
1
2
b
Entry
R
R
Product Yield (%)
(2a) 4a
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
Sc(OTf)
Sc(OTf)
Bi(OTf)
In(OTf)
FeCl
Dy(OTf)
Yb(OTf)
Cu(OTf)
Cu(OTf)
3
3
(10)
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
MeCN
25
60
60
60
60
60
60
60
60
60
60
60
60
60
25
60
60
60
60
60
—
—
—
—
—
—
16
68
60
83
67
44
—
—
67
55
77
83
81
41
72
82
86
86
79
89
72
—
—
—
—
—
91
84
—
—
—
—
—
—
(10)
(10)
(10)
1
2
3
4
5
6
7
8
C
C
C
C
C
C
C
C
C
C
6
H
6
H
6
H
6
H
6
H
6
H
6
H
6
H
6
H
6
H
5
5
5
5
5
5
5
5
5
5
(1a)
(1a)
(1a)
(1a)
(1a)
(1a)
(1a)
(1a)
(1a)
(1a)
4-MeOC
4-FC
6 4
4-ClC H
6
H
4
83
78
79
79
83
83
91
78
61
27
82
98
96
65
67
58
53
79
64
80
38
3
6
H
4
(2b)
(2c)
4b
4c
4d
4e
3
3
(10)
C
6
H
5
(2d)
4-MeC
3-NO
3-CF
3
(10)
6 4
H (2e)
3
(10)
(10)
(5)
2
C
6
H
4
(2f) 4f
(2g) 4g
2
3
C
6
H
4
2
2-Pyridinyl (2h) 4h
0
1
2
3
4
5
6
7
8
9
0
CuI (10)
CuI (5)
CuI (1)
9
C
6
H
5
CH
n-Hexyl (2j)
4-MeOC
4-FC
2
(2i)
4i
4j
10
11
12
13
14
15
16
17
18
19
n-C
n-C
n-C
n-C
n-C
n-C
n-C
5
H
H
H
H
H
H
H
11
11
11
11
C
C
C
C
(1c)
(1c)
(1c)
6
6
6
6
H
H
H
H
4
4
4
4
(1b)
6
H
4
(2a) 4k
AuCl
3
(10)
5
5
5
4
4
4
(1b)
(1b)
(1b)
6
H
4
(2b)
(2d)
2
CH (2i)
4l
4m
4n
AuCl (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
CuI (10)
C
C
6
H
H
5
6
5
9
9
9
4-MeOC
4-FC
6 5
C H (2d)
6 4
H (2a) 4o
(2b)
CH Cl
Toluene
THF
2
2
6
H
4
4p
4q
1-Cyclohexenyl (1d) 4-MeOC
1-Cyclohexenyl (1d) 4-FC
1-Cyclohexenyl (1d)
1-Cyclohexenyl (1d)
6
H
4
(2a) 4r
c
H
2
O
6
H
4
(2b)
(2d)
CH
4s
4t
4u
2
2
0
1
C
C
6
H
H
5
DCE: 1,2-dichloroethane.
Reaction conditions: 2-alkynyl benzaldehyde 1a (0.50 mmol), p-anisidine
0.50 mmol), diethyl phosphite (1.2 equiv), Lewis acid (cat.), solvent
3.0 mL).
Isolated yield based on 2-alkynyl benzaldehyde 1a.
In the presence of 20% SDS.
6
5
2
(2i)
a
a
(
(
Reaction conditions: 2-alkynyl benzaldehyde 1 (0.50 mmol), amine 2
(0.50 mmol), diethyl phosphate 3 (1.2 equiv), CuI (10 mol %), DCE
(3.0 mL), 60 C, 4 h.
Isolated yield based on 2-alkynyl benzaldehyde 1.
b
c
ꢀ
b

12168
Q. Ding et al. / Tetrahedron 63 (2007) 12166–12171
applied to pyridine derivative 2h, and 78% yield of the
desired product 4h was furnished (Table 2, entry 8).
0.25 mm 230–400 mesh silica gel impregnated with a fluo-
rescent indicator (254 nm). Solvents were re-distilled prior
to use in the reactions. Other commercial reagents were
used as-received. 2-Alkynyl benzaldehyde 1 was synthe-
sized via Sonogashira coupling according to the literature
As shown in Table 1, the reaction of 2-alkynyl benzaldehyde
1
a, p-anisidine 2a, and diethyl phosphate 3 proceeded
6
a
through compound 5a, which may presumably involve the
formation of p-complex via coordination of the alkynyl moi-
ety of 5a to Cu(I), thus activating the triple bond for nucleo-
philic attack by the amino group in the endo mode. However,
the reaction of compound 5a in the presence of CuI
report.
4.2. General procedure
A mixture of 2-alkynyl benzaldehyde 1 (0.5 mmol), amine 2
(0.5 mmol, 1.0 equiv), diethyl phosphite 3 (0.6 mmol,
1.2 equiv), and CuI (10 mol %) in dichloroethane (3.0 mL)
(
5 mol %) afforded the desired product 4a only in 14% yield.
Recently, an unexpected result for the reaction of compound
a catalyzed by Pd(II) was observed. 2H-Isoindol-1-yl-
phosphonate 6 was generated instead of 1,2-dihydro-
ꢀ
5
was stirred at 60 C under nitrogen atmosphere. After com-
pletion of the reaction as indicated by TLC, the reaction mix-
ture was quenched with water (10 mL) and extracted with
EtOAc (2ꢁ10 mL). Evaporation of the solvent followed by
purification of the residue on silica gel afforded pure 1,2-
dihydroisoquinolin-1-ylphosphonate 4.
1
2
isoquinolin-1-ylphosphonate 4a (Scheme 2, Eq. 1).
Interestingly, when palladium(II) was employed in the reac-
tion of 2-alkynyl benzaldehyde 1a, p-anisidine 2a, and
diethyl phosphate 3, 1,2-dihydroisoquinolin-1-ylphospho-
nate 4a was obtained in good yield [Pd(PPh ) Cl : 79%
3
2
2
yield, PdCl : 81% yield] (Scheme 2, Eq. 2). This observation
2
4.2.1. Diethyl 2-(4-methoxyphenyl)-3-phenyl-1,2-dihy-
droisoquinolin-1-ylphosphonate (4a). Yield 83%, yellow
liquid. H NMR (400 MHz, CDCl ) d 1.20–1.25 (m, 6H),
3
indicated that the reaction mechanism might be similar to
that described by Asao and Yamamoto.
1
0b
1
3
6
.65 (s, 3H), 3.90–4.12 (m, 4H), 5.33 (d, J¼19.0 Hz, 1H),
13
.44 (s, 1H), 6.63 (d, J¼8.8 Hz, 2H), 7.05 (d, J¼8.8 Hz,
EtO
EtO
O
2H), 7.06–7.28 (m, 7H), 7.57 (d, J¼8.8 Hz, 2H); C NMR
EtO
P
O
R
EtO
P
Pd(PhCN)2Cl2
(5 mol%)
(100 MHz, CDCl ) d 16.5, 55.3, 62.5, 62.6, 64.9, 111.1,
113.9, 124.1, 124.5, 125.0, 126.4, 127.3, 127.5, 127.8,
3
NHR
N
(1)
CH3CN
31
1
27.9, 128.2, 133.3, 137.5, 141.5, 142.6, 155.4; P NMR
9
2% yield
Ph
Ph
ꢂ1
(161 MHz, CDCl ) d 21.25; IR (cm ) nmax 1031 (P–O),
R = 4-MeOC6H4
3
5a
6
+
1050 (P–O), 1246 (P]O); MS (ESI) m/z 450.20 (M +1).
HRMS calcd for C H NO P: 449.1756, found: 449.1752.
Pd(PhCN) Cl
OMe
2
2
EtO
or
CHO
O
N
26 28
4
EtO
P
PdCl2 (5 mol%)
CH3CN
+
+ HP(O)(OEt)2
R (2)
4.2.2. Diethyl 2-(4-fluorophenyl)-3-phenyl-1,2-dihydro-
isoquinolin-1-ylphosphonate (4b). Yield 78%, yellow liq-
uid. H NMR (400 MHz, CDCl ) d 1.20–1.25 (m, 6H),
3
Ph
79 or 81% yield
R = 4-MeOC6H4
NH2
Ph
1
1
a
2a
3
4a
3
6
.90–4.12 (m, 4H), 5.34 (d, J¼18.6 Hz, 1H), 6.47 (s, 1H),
Scheme 2.
.7 (t, J¼10.6 Hz, 2H), 7.04–7.28 (m, 9H), 7.56 (d,
1
3
J¼8.0 Hz, 2H); C NMR (100 MHz, CDCl ) d 16.4, 62.6,
3
64.5, 111.8, 115.0, 115.3, 124.3, 124.4, 125.2, 126.6, 127.2,
127.7, 128.0, 128.3, 133.0, 137.1, 142.1, 143.9, 158.5;
3
1
3. Conclusion
P
NMR (161 MHz, CDCl ) d 20.92; IR (cm ) nmax 1025 (P–
ꢂ1
3
In summary, we have described copper(I) iodide catalyzed
three-component reactions of 2-alkynyl benzaldehydes,
amines, and diethyl phosphite, which provide a facile and
efficient route to 2,3-disubstituted-1,2-dihydroisoquinolin-
O), 1050 (P–O), 1251 (P]O); MS (ESI) m/z 438.20
(M +1). HRMS calcd for C H FNO P: 437.1556, found:
437.1561.
+
2
5
25
3
1
-ylphosphonates. Isoquinolinium intermediate may be in-
4.2.3. Diethyl 2-(4-chlorophenyl)-3-phenyl-1,2-dihydro-
isoquinolin-1-ylphosphonate (4c). Yield 79%, white solid.
H NMR (400 MHz, CDCl ) d 1.20–1.25 (m, 6H), 3.90–4.12
3
volved in the reaction process. The efficiency of this method
combined with the operational simplicity of the present pro-
cess makes it potentially attractive for library construction.
The focused library generation and screening for biological
activity of these small molecules are under investigation in
our laboratory.
1
(m, 4H), 5.37 (d, J¼18.6 Hz, 1H), 6.49 (s, 1H), 7.02–7.05
1
3
(m, 4H), 7.10–7.26 (m, 7H), 7.55 (d, J¼6.8 Hz, 2H);
C
NMR (100 MHz, CDCl ) d 16.4, 62.6, 62.7, 64.0, 112.5,
3
123.7, 124.4, 125.5, 126.7, 127.2, 127.5, 127.6, 128.1,
1
31
28.4, 128.5, 132.8, 136.9, 141.6, 146.2; P NMR
161 MHz, CDCl ) d 20.59; IR (cm ) nmax 1026 (P–O),
ꢂ1
(
1051 (P–O), 1265 (P]O); MS (ESI) m/z 454.20 (M +1).
3
+
4
. Experimental section
HRMS calcd for C H ClNO P: 453.1261, found:
2
5
25
3
4
.1. General
453.1257. Anal. Calcd for C H ClNO P: C, 66.15; H,
25 25 3
5
.55; N, 3.09. Found: C, 66.34; H, 5.86; N, 3.21.
All reactions were performed in test tubes under nitrogen at-
mosphere. Flash column chromatography was performed us-
˚
ing silica gel (60 A pore size, 32–63 mm, standard grade,
4.2.4. Diethyl 2,3-diphenyl-1,2-dihydroisoquinolin-1-yl-
phosphonate (4d). Yield 79%, yellow liquid. H NMR
1
Sorbent Technologies). Analytical thin-layer chromato-
graphy was performed using glass plates pre-coated with
(400 MHz, CDCl ) d 1.20–1.25 (m, 6H), 3.90–4.10 (m,
3
4H), 5.45 (d, J¼18.6 Hz, 1H), 6.50 (s, 1H), 6.85–6.87 (m,

Q. Ding et al. / Tetrahedron 63 (2007) 12166–12171
12169
1
3
ꢂ1
1
(
H), 7.07–7.25 (m, 11H), 7.58 (d, J¼6.8 Hz, 2H); C NMR
IR (cm ) nmax 1029 (P–O), 1050 (P–O), 1265 (P]O);
MS (ESI): m/z 421.20 (M +1). HRMS calcd for
+
100 MHz, CDCl ) d 16.4, 62.5, 62.7, 64.2, 112.2, 122.3,
3
1
1
22.6, 124.3, 125.6, 126.5, 127.2, 127.6, 127.9, 128.2,
28.5, 133.0, 137.3, 142.0, 147.6; P NMR (161 MHz,
C H N O P: 420.1603, found: 420.1606. Anal. Calcd for
2
C H N O P: C, 68.56; H, 5.99; N, 6.66. Found: C,
24 25 2 3
68.33; H, 5.82; N, 6.83.
4 25 2 3
3
1
ꢂ1
CDCl ) d 21.33; IR (cm ) nmax 1025 (P–O), 1052 (P–O),
3
1251 (P]O); MS (ESI) m/z 420.20 (M +1). HRMS calcd
for C H NO P: 419.1650, found: 419.1654.
+
4.2.9. Diethyl 2-benzyl-3-phenyl-1,2-dihydroisoquinolin-
1-ylphosphonate (4i). Yield 61%, colorless liquid.
25
26
3
1
H
4
1
.2.5. Diethyl 3-phenyl-2-p-tolyl-1,2-dihydroisoquinolin-
-ylphosphonate (4e). Yield 83%, yellow liquid. H NMR
NMR (400 MHz, CDCl ) d 1.15 (t, J¼7.2 Hz, 3H), 1.22 (t,
3
1
J¼7.2 Hz, 3H), 3.80–3.95 (m, 3H), 4.00–4.16 (m, 2H),
4.30 (d, J¼15.6 Hz, 1H), 4.81 (d, J¼18.6 Hz, 1H), 5.97 (s,
1H), 6.90–6.95 (m, 1H), 7.04–7.08 (m, 2H), 7.15–7.20 (m,
(
400 MHz, CDCl ) d 1.20–1.25 (m, 6H), 2.16 (s, 3H),
3
3
6
.88–4.13 (m, 4H), 5.40 (d, J¼19.0 Hz, 1H), 6.47 (s, 1H),
1
3
.88 (d, J¼8.4 Hz, 2H), 6.98 (d, J¼8.4 Hz, 2H), 7.09–7.25
6H), 7.35–7.40 (m, 3H), 7.69 (d, J¼6.8 Hz, 2H);
C
NMR (100 MHz, CDCl ) d 16.4, 16.5, 55.9, 59.2, 62.2,
1
3
(
(
m, 7H), 7.58 (dd, J¼8.8, 2.0 Hz, 2H); C NMR
100 MHz, CDCl ) d 16.4, 20.5, 62.4, 62.6, 64.4, 111.7,
3
62.4, 107.1, 123.6, 124.3, 125.9, 127.1, 127.2, 127.8,
128.0, 128.1, 128.3, 128.4, 128.5, 134.0, 137.5, 138.5,
146.9; P NMR (161 MHz, CDCl ) d 21.92; IR (cm )
3
1
1
22.7, 124.1, 125.3, 126.4, 127.2, 127.6, 127.8, 128.1,
28.2, 129.1, 131.8, 133.1, 137.4, 142.2, 145.4; P NMR
3
1
31
ꢂ1
3
ꢂ1
(
161 MHz, CDCl ) d 21.31; IR (cm ) nmax 1026 (P–O),
3
nmax 1027 (P–O), 1052 (P–O), 1248 (P]O); MS (ESI): m/z
434.20 (M +1). HRMS calcd for C H NO P: 433.1807,
found: 433.1802.
+
+
1
HRMS calcd for C H NO P: 433.1807, found 433.1804.
052 (P–O), 1248 (P]O); MS (ESI): 434.20 (M +1);
2
6
28
3
2
6
28
3
Anal. Calcd for C H NO P: C, 72.04; H, 6.51; N, 3.23.
3
2
6
28
Found: C, 72.41; H, 6.33; N, 3.42.
4.2.10. Diethyl 2-hexyl-3-phenyl-1,2-dihydroisoquinolin-
1-ylphosphonate (4j). Yield 27%, yellow liquid. H NMR
1
4
.2.6. Diethyl 2-(3-nitrophenyl)-3-phenyl-1,2-dihydroiso-
quinolin-1-ylphosphonate (4f). Yield 83%, yellow liquid.
(400 MHz, CDCl ) d 0.74 (t, J¼6.8 Hz, 3H), 1.00–1.17
3
(m, 6H), 1.19 (t, J¼7.2 Hz, 3H), 1.25 (t, J¼7.2 Hz, 3H),
1.40–1.42 (m, 2H), 2.91–2.95 (m, 1H), 3.17–3.21 (m, 1H),
3.86–4.11 (m, 4H), 4.86 (d, J¼18.6 Hz, 1H), 5.87 (s, 1H),
7.00 (d, J¼8.0 Hz, 1H), 7.12–7.15 (m, 2H), 7.18–7.22 (m,
1
H NMR (400 MHz, CDCl ) d 1.20–1.25 (m, 6H), 3.94–
3
3
6
1
.98 (m, 2H), 4.07–4.09 (m, 2H), 5.43 (d, J¼18.6 Hz, 1H),
.57 (s, 1H), 7.18–7.34 (m, 10H), 7.55 (d, J¼8.0 Hz, 2H),
48.3 (d, J¼7.0 Hz), 7.68 (d, J¼7.2 Hz, 1H), 7.93 (s, 1H);
1
3
1H), 7.32–7.40 (m, 3H), 7.58–7.62 (m, 2H); C NMR
1
3
C NMR (100 MHz, CDCl ) d 16.4, 62.8, 62.9, 63.4,
(100 MHz, CDCl ) d 13.8, 16.4, 16.5, 22.3, 26.1, 28.6,
3
3
1
1
1
13.9, 116.4, 116.6, 124.8, 125.8, 127.1, 127.2, 127.5,
27.8, 128.4, 128.6, 128.7, 129.0, 132.4, 136.3, 140.7,
48.3, 148.5; P NMR (161 MHz, CDCl ) d 20.19; IR
31.3, 53.3, 60.5, 62.2, 62.4, 106.7, 123.4, 124.4, 125.8,
126.9, 128.1, 128.2, 134.3, 137.8, 146.8; P NMR
(161 MHz, CDCl ) d 21.59; IR (cm ) nmax 1027 (P–O),
3
1
3
1
ꢂ1
3
3
ꢂ1
+
(cm ) nmax 1022 (P–O), 1050 (P–O), 1264 (P]O); MS
ESI): m/z 465.20 (M +1). HRMS calcd for C H N O P:
1050 (P–O), 1245 (P]O); MS (ESI): m/z 428.20 (M +1).
HRMS calcd for C H NO P: 427.2276, found: 427.2273.
+
(
2
5
25
2
5
25 34
3
4
64.1501, found: 464.1505.
4.2.11. Diethyl 2-(4-methoxyphenyl)-3-(4-pentylphenyl)-
1,2-dihydroisoquinolin-1-ylphosphonate (4k). Yield 82%,
yellow liquid. H NMR (400 MHz, CDCl ) d 0.86 (t,
3
4
1
.2.7. Diethyl 3-phenyl-2-(3-(trifluoromethyl)phenyl)-
,2-dihydroisoquinolin-1-ylphosphonate (4g). Yield 91%,
1
1
white solid. H NMR (400 MHz, CDCl ) d 1.20 (t,
3
J¼6.8 Hz, 3H), 1.21–1.25 (m, 6H), 1.28–1.32 (m, 4H),
1.55–1.60 (m, 2H), 2.51 (t, J¼8.0 Hz, 2H), 3.65 (s, 3H),
3.90–4.12 (m, 4H), 5.32 (d, J¼19.0 Hz, 1H), 6.41 (s, 1H),
6.62 (d, J¼8.8 Hz, 2H), 7.02–7.05 (m, 4H), 7.06–7.18 (m,
J¼7.2 Hz, 3H), 1.25 (t, J¼7.2 Hz, 3H), 3.94–3.96 (m, 2H),
4
7
7
2
1
1
1
.07–4.09 (m, 2H), 5.42 (d, J¼18.6 Hz, 1H), 6.53 (s, 1H),
.08–7.10 (m, 1H), 7.16–7.18 (m, 4H), 7.19–7.24 (m, 3H),
.25–7.29 (m, 2H), 7.34 (s, 1H), 7.53 (dd, J¼6.8, 1.6 Hz,
1
3
3H), 7.22 (d, J¼7.2 Hz, 1H), 7.47 (d, J¼8.4 Hz, 2H);
C
13
H); C NMR (100 MHz, CDCl ) d 16.4, 62.6, 62.9, 63.6,
NMR (100 MHz, CDCl ) d 13.9, 16.4, 22.4, 30.8, 31.5,
3
3
13.2, 118.6, 123.9, 124.6, 125.4, 125.7, 126.9, 127.2,
27.6, 128.2, 128.4, 128.5, 128.9, 130.9, 132.7, 136.8,
41.3, 147.8; P NMR (161 MHz, CDCl ) d 20.72; IR
35.6, 55.2, 62.4, 62.6, 64.85, 110.3, 113.7, 123.9, 124.4,
124.8, 126.1, 127.2, 127.6, 128.1, 128.2, 133.3, 134.6,
141.6, 142.5, 142.7, 155.1; P NMR (161 MHz, CDCl3)
3
1
31
3
ꢂ1
ꢂ1
(
(
cm ) nmax 1026 (P–O), 1050 (P–O), 1250 (P]O); MS
ESI): m/z 488.20 (M +1). HRMS calcd for C H F NO P:
d 21.26; IR (cm ) nmax 1028 (P–O), 1054 (P–O), 1264
(P]O); MS (ESI): m/z 520.30 (M +1). HRMS calcd for
+
+
2
6
25
3
3
4
C, 64.06; H, 5.17; N, 2.87. Found: C, 64.43; H, 5.11; N, 3.21.
87.1524, found 487.1521. Anal. Calcd for C H F NO P:
C H NO P: 519.2538, found: 519.2534.
31 38 4
2
6
25
3
3
4
.2.12. Diethyl 2-(4-fluorophenyl)-3-(4-pentylphenyl)-
1,2-dihydroisoquinolin-1-ylphosphonate (4l). Yield 98%,
4.2.8. Diethyl 3-phenyl-2-(pyridin-2-yl)-1,2-dihydroiso-
quinolin-1-ylphosphonate (4h). Yield 78%, white solid.
1
yellow liquid. H NMR (400 MHz, CDCl ) d 0.86 (t,
3
1
H NMR (400 MHz, CDCl ) d 1.12 (t, J¼7.2 Hz, 3H),
J¼7.2 Hz, 3H), 1.21–1.25 (m, 6H), 1.28–1.34 (m, 4H),
1.56–1.62 (m, 2H), 2.52 (t, J¼7.6 Hz, 2H), 3.90–4.12 (m,
4H), 5.32 (d, J¼18.6 Hz, 1H), 6.44 (s, 1H), 6.77 (t,
J¼8.8 Hz, 2H), 7.03–7.06 (m, 4H), 7.09–7.19 (m, 3H),
3
1
2
.19 (t, J¼7.2 Hz, 3H), 3.95–3.98 (m, 2H), 4.11–4.13 (m,
H), 6.60 (t, J¼4.4 Hz, 1H), 6.65 (s, 1H), 6.80 (d,
J¼21.0 Hz, 1H), 7.19–7.37 (m, 8H), 7.62 (d, J¼7.2 Hz,
1
3
13
2
d 16.2, 16.3, 55.8, 62.5, 62.6, 113.0, 116.3, 125.5, 125.9,
H), 8.24 (d, J¼4.4 Hz, 2H); C NMR (100 MHz, CDCl )
7.24 (t, J¼7.2 Hz, 1H), 7.45 (d, J¼8.4 Hz, 2H); C NMR
3
(100 MHz, CDCl ) d 13.9, 16.4, 22.4, 30.8, 31.5, 35.6,
3
1
1
26.9, 127.0, 127.1, 127.3, 128.1, 129.1, 132.8, 138.4,
39.8, 157.2, 160.0; P NMR (161 MHz, CDCl ) d 21.82;
62.6, 64.5, 110.1, 115.1, 124.1, 124.2, 124.3, 125.1, 126.3,
127.1, 127.5, 128.2, 133.1, 134.3, 142.1, 143.0, 144.0,
31
3

12170
Q. Ding et al. / Tetrahedron 63 (2007) 12166–12171
3
1
ꢂ1
1
nmax 1025 (P–O), 1051 (P–O), 1253 (P]O); MS (ESI): m/z
58.43; P NMR (161 MHz, CDCl ) d 20.92; IR (cm
)
32.9, 62.3, 62.7, 64.8, 109.1, 115.4, 123.2, 125.6, 125.8,
125.9, 127.0, 128.1, 133.1, 143.3, 144.0, 159.4; P NMR
3
3
1
+
ꢂ1
508.30 (M +1). HRMS calcd for C H FNO P: 507.2339,
3
found: 507.2335.
(161 MHz, CDCl ) d 20.70; IR (cm ) nmax 1025 (P–O),
3
0
35
3
+
1049 (P–O), 1250 (P]O); MS (ESI): m/z 416.20 (M ꢂ1).
HRMS calcd for C H FNO P: 417.1869, found 417.1864.
3
2
3
29
4.2.13. Diethyl 3-(4-pentylphenyl)-2-phenyl-1,2-dihy-
droisoquinolin-1-ylphosphonate (4m). Yield 96%, yellow
4.2.17. Diethyl 3-butyl-2-phenyl-1,2-dihydroisoquinolin-
1-ylphosphonate (4q). Yield 53%, yellow liquid. H NMR
1
1
liquid. H NMR (400 MHz, CDCl ) d 0.86 (t, J¼7.2 Hz,
3
3
2
H), 1.22–1.26 (m, 6H), 1.26–1.30 (m, 4H), 1.55–1.60 (m,
H), 2.51 (t, J¼8.0 Hz, 2H), 3.89–4.12 (m, 4H), 5.44 (d,
(400 MHz, CDCl ) d 0.84 (t, J¼7.2 Hz, 3H), 1.22–1.28
3
(m, 8H), 1.56–1.60 (m, 2H), 2.17–2.21 (m, 1H), 2.33–2.36
(m, 1H), 3.86–4.02 (m, 4H), 5.15 (d, J¼19.0 Hz, 1H), 6.04
J¼18.6 Hz, 1H), 6.47 (s, 1H), 6.85–6.90 (m, 1H), 7.03 (d,
1
3
J¼8.0 Hz, 2H), 7.07–7.10 (m, 4H), 7.12–7.16 (m, 2H),
(s, 1H), 6.97–7.06 (m, 4H), 7.18–7.26 (m, 5H); C NMR
(100 MHz, CDCl ) d 13.8, 16.4, 22.4, 30.3, 32.9, 62.2,
7
2
3
1
1
.18–7.22 (m, 1H), 7.23–7.25 (m, 1H), 7.47 (d, J¼8.0 Hz,
3
1
3
H); C NMR (100 MHz, CDCl ) d 13.9, 16.4, 22.4, 30.8,
3
62.7, 64.6, 109.8, 123.2, 123.3, 123.6, 123.7, 125.6, 127.0,
128.1, 128.7, 133.2, 144.0, 147.2; P NMR (161 MHz,
3
1
1.4, 35.5, 62.4, 62.6, 64.1, 111.5, 122.1, 122.6, 124.1,
25.5, 126.3, 127.1, 127.4, 128.1, 128.2, 128.4, 133.2,
34.6, 142.0, 142.8, 147.8; P NMR (161 MHz, CDCl3)
ꢂ1
CDCl ) d 20.91; IR (cm ) nmax 1024 (P–O), 1050 (P–O),
3
3
1
+
1253 (P]O); MS (ESI): m/z 400.20 (M +1). HRMS calcd
for C H NO P: 399.1963, found 399.1967.
ꢂ1
d 21.34; IR (cm ) nmax 1027 (P–O), 1053 (P–O), 1251
(P]O); MS (ESI): m/z 490.30 (M +1). HRMS calcd for
C H NO P: 489.2433, found: 489.2437.
23
30
3
+
4.2.18. Diethyl 3-cyclohexenyl-2-(4-methoxyphenyl)-1,2-
dihydroisoquinolin-1-ylphosphonate (4r). Yield 79%,
3
0
36
3
1
4
.2.14. Diethyl 2-benzyl-3-(4-pentylphenyl)-1,2-dihydro-
isoquinolin-1-ylphosphonate (4n). Yield 65%, yellow liq-
yellow liquid. H NMR (400 MHz, CDCl ) d 1.24–1.30
3
(m, 6H), 1.46–1.52 (m, 4H), 1.92–2.12 (m, 4H), 3.74 (s,
3H), 3.93–4.07 (m, 4H), 5.16 (d, J¼19.6 Hz, 1H), 6.13 (t,
J¼4.0 Hz, 1H), 6.20 (s, 1H), 6.73 (t, J¼8.8 Hz, 2H), 7.02–
1
uid. H NMR (400 MHz, CDCl ) d 0.89 (t, J¼6.8 Hz, 3H),
3
1
.15 (t, J¼7.2 Hz, 3H), 1.22 (t, J¼7.2 Hz, 3H), 1.34–1.40
1
3
(
4
m, 4H), 1.63–1.66 (m, 2H), 2.62 (t, J¼7.6 Hz, 2H), 3.83–
7.08 (m, 5H), 7.18–7.22 (m, 1H); C NMR (100 MHz,
.09 (m, 4H), 4.13 (dd, J¼15.6, 3.2 Hz, 1H), 4.32 (d,
CDCl ) d 16.4, 22.0, 22.6, 25.6, 26.2, 55.3, 62.3, 62.5,
3
J¼15.6 Hz, 1H), 4.80 (d, J¼18.6 Hz, 1H), 5.94 (s, 1H),
64.6, 108.9, 113.6, 123.5, 123.9, 124.7, 125.8, 127.1,
127.9, 129.4, 133.3, 133.6, 142.4, 144.5, 155.2; P NMR
3
1
6
7
.90–6.95 (m, 1H), 7.02–7.05 (m, 2H), 7.14–7.21 (m, 8H),
.59 (d, J¼8.0 Hz, 2H); C NMR (100 MHz, CDCl3)
1
3
ꢂ1
(161 MHz, CDCl ) d 21.12; IR (cm ) nmax 1026 (P–O),
3
+
d 13.9, 16.4, 16.5, 22.4, 31.0, 31.5, 35.7, 55.8, 59.2, 62.1,
1050 (P–O), 1252 (P]O); MS (ESI): m/z 452.20 (M ꢂ1).
6
1
1
2.3, 106.4, 123.4, 124.2, 125.7, 127.0, 127.1, 127.7,
27.9, 128.0, 128.2, 128.4, 134.1, 134.7, 138.6, 143.5,
46.9; P NMR (161 MHz, CDCl ) d 21.05; IR (cm )
HRMS calcd for C H NO P: 453.2069, found: 453.2065.
2
6
32
4
3
1
ꢂ1
4.2.19. Diethyl 3-cyclohexenyl-2-(4-fluorophenyl)-1,2-di-
hydroisoquinolin-1-ylphosphonate (4s). Yield 64%, yel-
3
nmax 1026 (P–O), 1052 (P–O), 1264 (P]O); MS (ESI): m/z
+
1
5
found: 503.2584.
04.30 (M +1). HRMS calcd for C H NO P: 503.2589,
3
low liquid. H NMR (400 MHz, CDCl ) d 1.24–1.30 (m,
3
1
38
3
6H), 1.45–1.56 (m, 4H), 1.90–2.13 (m, 4H), 3.92–4.08 (m,
4
H), 5.17 (d, J¼19.6 Hz, 1H), 6.11 (t, J¼4.0 Hz, 1H), 6.24
4
.2.15. Diethyl 3-butyl-2-(4-methoxyphenyl)-1,2-dihy-
droisoquinolin-1-ylphosphonate (4o). Yield 67%, yellow
(s, 1H), 6.87 (t, J¼8.8 Hz, 2H), 7.04–7.10 (m, 5H), 7.20–
1
3
7.24 (m, 1H); C NMR (100 MHz, CDCl ) d 16.4, 22.0,
3
1
solid. H NMR (400 MHz, CDCl ) d 0.83 (t, J¼7.2 Hz,
22.6, 25.6, 26.2, 62.4, 62.5, 64.4, 109.7, 115.0, 123.4,
124.1, 125.0, 126.1, 127.1, 128.1, 129.7, 133.1, 133.2,
3
3H), 1.20–1.38 (m, 8H), 1.50–1.55 (m, 2H), 2.09–1.13 (m,
1H), 2.26–2.30 (m, 1H), 3.77 (s, 3H), 4.01–3.87 (m, 4H),
5.03 (d, J¼18.6 Hz, 1H), 5.93 (s, 1H), 6.79 (d, J¼8.0 Hz,
2H), 6.99 (d, J¼8.0 Hz, 2H), 7.05 (t, J¼7.6 Hz, 1H), 7.14–
7
3
1
144.0, 144.9, 158.47;
d 20.86; IR (cm ) nmax 1031 (P–O), 1050 (P–O), 1249
P NMR (161 MHz, CDCl3)
ꢂ1
+
(P]O); MS (ESI): m/z 442.20 (M +1). HRMS calcd for
C H FNO P: 441.1869, found: 441.1865.
1
3
.16 (m, 1H), 7.18 (d, J¼8.8 Hz, 2H);
C NMR
2
5
29
3
(
100 MHz, CDCl ) d 13.8, 16.4, 22.3, 30.2, 33.0, 55.4,
3
6
1
2.2, 62.6, 65.03, 107.8, 113.9, 123.0, 125.4, 126.0, 127.0,
28.0, 129.7, 133.4, 140.6, 144.7, 156.3;
4.2.20. Diethyl 3-cyclohexenyl-2-phenyl-1,2-dihydroiso-
quinolin-1-ylphosphonate (4t). Yield 80%, yellow liquid.
H NMR (400 MHz, CDCl ) d 1.24–1.31 (m, 6H), 1.45–
3
3
1
P NMR
ꢂ1
1
(
161 MHz, CDCl ) d 21.02; IR (cm ) nmax 1025 (P–O),
3
+
1
HRMS calcd for C H NO P: 429.2069, found: 429.2065.
Anal. Calcd for C H NO P: C, 67.12; H, 7.51; N, 3.26.
32
050 (P–O), 1251 (P]O); MS (ESI): m/z 428.30 (M ꢂ1).
1.58 (m, 4H), 1.92–2.15 (m, 4H), 3.92–4.05 (m, 4H), 5.29
(d, J¼19.6 Hz, 1H), 6.13 (t, J¼4.0 Hz, 1H), 6.27 (s, 1H),
6.92 (t, J¼6.8 Hz, 1H), 7.03–7.10 (m, 5H), 7.16–7.20 (m,
24
32
4
24
4
1
3
Found: C, 67.44; H, 7.70; N, 3.45.
3H); C NMR (100 MHz, CDCl ) d 16.4, 22.1, 22.6, 25.7,
3
2
6.2, 62.4, 62.6, 64.0, 110.0, 121.7, 122.0, 124.2, 125.5,
126.0, 127.1, 128.0, 128.4, 129.4, 133.2, 133.4, 144.0,
4.2.16. Diethyl 3-butyl-2-(4-fluorophenyl)-1,2-dihydro-
isoquinolin-1-ylphosphonate (4p). Yield 58%, yellow liq-
3
1
ꢂ1
148.7; P NMR (161 MHz, CDCl ) d 20.83; IR (cm )
3
1
uid. H NMR (400 MHz, CDCl ) d 0.84 (t, J¼7.2 Hz, 3H),
nmax 1025 (P–O), 1050 (P–O), 1248 (P]O); MS (ESI): m/z
424.30 (M +1). HRMS calcd for C H NO P: 423.1963,
found: 423.1966.
3
+
1
2
.20–1.38 (m, 8H), 1.52–1.56 (m, 2H), 2.12–2.15 (m, 1H),
.26–2.30 (m, 1H), 3.88–4.05 (m, 4H), 5.04 (d,
2
5
30
3
J¼18.6 Hz, 1H), 5.99 (s, 1H), 6.95 (t, J¼8.0 Hz, 2H), 7.00
(
d, J¼8.0 Hz, 2H), 7.08 (t, J¼7.6 Hz, 1H), 7.20–7.25 (m,
4.2.21. Diethyl 2-benzyl-3-cyclohexenyl-1,2-dihydroiso-
quinolin-1-ylphosphonate (4u). Yield 38%, yellow liquid.
1
3
3
H); C NMR (100 MHz, CDCl ) d 13.8, 16.4, 22.3, 30.1,
3

Q. Ding et al. / Tetrahedron 63 (2007) 12166–12171
12171
1
H NMR (400 MHz, CDCl ) d 1.20–1.25 (m, 6H), 1.58–1.78
3
38, 7687; (g) Khan, M. W.; Kundu, N. G. Synlett 1997, 1435;
(h) Ohe, K.; Ishihara, T.; Chatani, N.; Kawasaki, Y.; Murai,
S. J. Org. Chem. 1991, 56, 2267; (i) Nagarajan, A.;
Balasubramanian, T. R. Indian J. Chem., Sect. B 1989, 28,
67; (j) Sakamoto, T.; Kondo, Y.; Iwashita, S.; Nagano, T.;
Yamanaka, H. Chem. Pharm. Bull. 1988, 36, 1305; (k)
Taylor, E. C.; Katz, A. H.; Salgado-Zamora, H.; McKillop,
A. Tetrahedron Lett. 1985, 26, 5963.
(
(
(
m, 4H), 2.16–2.23 (m, 3H), 2.41–2.45 (m, 1H), 4.01–3.80
m, 4H), 4.14–4.20 (m, 2H), 4.61 (d, J¼19.6 Hz, 1H), 5.84
s, 1H), 6.31 (t, J¼4.0 Hz, 1H), 6.88 (d, J¼7.2 Hz, 1H),
6
.95 (d, J¼7.2 Hz, 1H), 7.00 (t, J¼7.2 Hz, 1H), 7.13 (t,
1
3
J¼7.2 Hz, 1H), 7.18–7.29 (m, 5H); C NMR (100 MHz,
CDCl ) d 16.4, 22.2, 22.7, 25.6, 27.1, 55.6, 58.5, 62.0,
3
6
1
2.2, 105.2, 123.6, 124.1, 125.5, 127.1, 127.3, 127.8,
27.9, 128.3, 128.4, 134.1, 134.2, 138.7, 149.0; P NMR
3
1
6. (a) Roesch, K. R.; Larock, R. C. J. Org. Chem. 2002, 67, 86; (b)
Zhang, H.; Larock, R. C. Tetrahedron Lett. 2002, 43, 1359.
7. (a) Melis, K.; Opstal, T.; Verpoort, F. Eur. J. Org. Chem. 2002,
22, 3779; (b) Anastasia, L.; Xu, C.; Negishi, E.-i. Tetrahedron
Lett. 2002, 43, 5673; (c) Bellina, F.; Ciucci, D.; Vergamini, P.;
Rossi, R. Tetrahedron 2000, 56, 2533; (d) Qing, F. L.; Gao,
W. Z. Tetrahedron Lett. 2000, 41, 7727; (e) Kundu, N. G.;
Pal, M.; Nandi, B. J. Chem. Soc., Perkin Trans. 1 1998, 561;
(f) Liao, H. Y.; Cheng, C. H. J. Org. Chem. 1995, 60, 3711;
(g) Ogawa, Y.; Maruno, M.; Wakamatsu, T. Heterocycles
1995, 41, 2587.
ꢂ1
(
161 MHz, CDCl ) d 21.32; IR (cm ) nmax 1025 (P–O),
3
+
1050 (P–O), 1252 (P]O); MS (ESI): m/z 438.30 (M +1).
HRMS calcd for C H NO P: 437.2120, found: 437.2122.
2
6
32
3
Acknowledgements
Financial support from National Natural Science Foundation
of China (20502004) and the Science & Technology Com-
mission of Shanghai Municipality (05ZR14013) is grate-
fully acknowledged.
8. (a) Trost, B. M.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124,
2
528; (b) Bates, C. G.; SaeJueng, P.; Murphy, J. M.;
Venkataraman, D. Org. Lett. 2002, 4, 4727; (c) Cutchins,
W. W.; McDonald, F. E. Org. Lett. 2002, 4, 749; (d)
Aschwanden, P.; Frantz, D. E.; Carreira, E. M. Org. Lett.
2000, 2, 2331; (e) McDonald, F. E.; Reddy, K. S.; Diaz, Y.
J. Am. Chem. Soc. 2000, 122, 4304.
References and notes
1
2
. (a) Schreiber, S. L. Science 2000, 287, 1964; (b) Mitchison,
T. J. Chem. Biol. 1994, 1, 3; (c) Schreiber, S. L. Bioorg. Med.
Chem. 1998, 6, 1127.
. For examples, see: (a) Ugi, I.; Domling, A.; Werner, B.
J. Heterocycl. Chem. 2000, 37, 647; (b) Bienaym ꢀe , H.;
Hulme, C.; Oddon, G.; Schmitt, P. Chem.—Eur. J. 2000, 6,
321; (c) Ugi, I.; Heck, S. Comb. Chem. High Throughput
Screen. 2001, 4, 1; (d) Zhu, J. Eur. J. Org. Chem. 2003, 1133;
e) Weber, L. Curr. Med. Chem. 2002, 9, 1241; (f) Orru,
R. V. A.; de Greef, M. Synthesis 2003, 1471; (g) D €o mling,
A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168; (h) Lee,
D.; Sello, J. K.; Schreiber, S. L. Org. Lett. 2000, 2, 709.
. (a) Wu, J.; Sun, W.; Sun, X.; Xia, H.-G. Green Chem. 2006, 8,
9. (a) Peng, A. Y.; Ding, Y. X. J. Am. Chem. Soc. 2003, 125,
15006; (b) Tang, W.; Ding, Y. X. J. Org. Chem. 2006, 71,
8489; (c) Peng, A. Y.; Ding, Y. X. Org. Lett. 2005, 7, 3299.
10. (a) Obika, S.; Kono, H.; Yasui, Y.; Yanada, R.; Takemoto, Y.
J. Org. Chem. 2007, 72, 4462 and references cited therein;
(b) Asao, N.; Yudha, S. S.; Nogami, T.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2005, 44, 5526; (c) Yanada, R.;
Obika, S.; Kono, H.; Takemoto, Y. Angew. Chem., Int. Ed.
2006, 45, 3822; (d) Asao, N.; Iso, K.; Yudha, S. S. Org. Lett.
2006, 8, 4149; (e) Mori, S.; Uerdingen, M.; Krause, N.;
Morokuma, K. Angew. Chem., Int. Ed. 2005, 44, 4715; (f)
Asao, N.; Chan, C. S.; Takahashi, K.; Yamamoto, Y.
Tetrahedron 2005, 61, 11322; (g) Ohtaka, M.; Nakamura, H.;
Yamamoto, Y. Tetrahedron Lett. 2004, 45, 7339; (h)
Witulski, B.; Alayrac, C.; Tevzadze-Saeftel, L. Angew.
Chem., Int. Ed. 2003, 42, 4257; (i) Yavari, I.; Ghazanfarpour-
Darjani, M.; Sabbaghan, M.; Hossaini, Z. Tetrahedron Lett.
2007, 48, 3749; (j) Shaabani, A.; Soleimani, E.; Khavasi,
H. R. Tetrahedron Lett. 2007, 48, 4743; (k) Wang, G.-W.; Li,
J.-X. Org. Biomol. Chem. 2006, 4, 4063; (l) Diaz, J. L.;
Miguel, M.; Lavilla, R. J. Org. Chem. 2004, 69, 3550.
3
(
3
4
365; (b) Wu, J.; Sun, W.; Xia, H.-G.; Sun, X. Org. Biomol.
Chem. 2006, 4, 1663.
. (a) Ma, C.; Liu, X.; Li, X.; Flippen-Anderson, J.; Yu, S.; Cook,
J. M. J. Org. Chem. 2001, 66, 4525; (b) Kondo, T.; Okada, T.;
Suzuki, T.; Mitusudi, T.-a. J. Organomet. Chem. 2001, 622,
1
49; (c) Muller, T. E.; Berger, M.; Grosche, M.; Herdtweck,
E.; Schmidtchen, F. P. Organometallics 2001, 20, 4384; (d)
Xu, L.; Lewis, I. R.; Davidsen, S. K.; Summers, J. B.
Tetrahedron Lett. 1998, 39, 5159; (e) Yu, M. S.; de Leon,
L. L.; McGuire, M. A.; Botha, G. Tetrahedron Lett. 1998, 39,
9
347; (f) Mahanty, J. S.; De, M.; Das, P.; Kundu, N. G.
11. (a) Huang, Q.; Larock, R. C. J. Org. Chem. 2003, 68, 980; (b)
Dai, G.; Larock, R. C. J. Org. Chem. 2003, 68, 920; (c) Dai, G.;
Larock, R. C. J. Org. Chem. 2002, 67, 7042; (d) Huang, Q.;
Hunter, J. A.; Larock, R. C. J. Org. Chem. 2002, 67, 3437;
(e) Roesch, K. R.; Zhang, H.; Larock, R. C. J. Org. Chem.
2001, 66, 8042; (f) Roesch, K. R.; Larock, R. C. Org. Lett.
1999, 1, 553.
12. For selected examples, see: (a) Zhang, L.; Wu, J. Adv. Synth.
Catal. 2007, 349, 1047; (b) Wang, W.; Ding, Q.; Fan, R.; Wu,
J. Tetrahedron Lett. 2007, 48, 3647; (c) Sun, W.; Ding, Q.;
Sun, X.; Fan, R.; Wu, J. J. Comb. Chem. 2007, 9, 690; (d)
Ding, Q.; Ye, Y.; Fan, R.; Wu, J. J. Org. Chem. 2007, 72, 5439.
13. Lewis Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-
VCH GmbH: D-69469, Germany, 2000.
Tetrahedron 1997, 53, 13397; (g) Cacchi, S.; Carnicelli, V.;
Marinelli, F. J. Organomet. Chem. 1994, 475, 289; (h)
Arcadi, A.; Cacchi, S.; Marinelli, F. Tetrahedron Lett. 1989,
30, 2581; (i) Utimoto, K.; Miwa, H.; Nozaki, H. Tetrahedron
Lett. 1981, 22, 4277.
. (a) Van Esseveldt, B. C. J.; van Delft, F. L.; de Gelder, R.;
Rutjes, F. P. J. T. Org. Lett. 2003, 5, 1717; (b) Kozawa, Y.;
Mori, M. Tetrahedron Lett. 2002, 43, 1499; (c) Torres, J. C.;
Pilli, R. A.; Vargas, M. D.; Violante, F. A.; Garden, S. J.;
Pinto, A. C. Tetrahedron 2002, 58, 4487; (d) Sashida, H.;
Kawamukai, A. Synthesis 1999, 1145; (e) Kobayashi, Y.;
Fukuyama, T. J. Heterocycl. Chem. 1998, 35, 1043; (f)
McDonald, F. E.; ChatterJee, A. K. Tetrahedron Lett. 1997,
5