An approach to 1-phosphorylated isoquinolines through silver(I)-catalyzed tandem reaction involving C-N and C-P bond formation

Article abstract of DOI:10.1016/j.tet.2014.06.060

A novel silver-catalyzed tandem reaction of 2-alkynylbenzaldoximes with H-phosphinate esters, and H-phosphine oxides has been developed, providing a general and powerful tool for the synthesis of various 1-phosphorylated isoquinolins in moderate to excellent yield. This reaction proceeded smoothly to construct C-N and C-P bonds in one-pot with good functional group tolerance under mild conditions.

Full text of DOI:10.1016/j.tet.2014.06.060

Tetrahedron 70 (2014) 5720e5724
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An approach to 1-phosphorylated isoquinolines through
silver(I)-catalyzed tandem reaction involving CeN and CeP
bond formation
,
Xianbo Wang a, Zhiyong Wang b
*
a Department of Chemistry, Nanchang University, Nanchang 330031, China
b School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400044, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 April 2014
Received in revised form 27 May 2014
Accepted 17 June 2014
Available online 20 June 2014
A novel silver-catalyzed tandem reaction of 2-alkynylbenzaldoximes with H-phosphinate esters, and
H-phosphine oxides has been developed, providing a general and powerful tool for the synthesis of
various 1-phosphorylated isoquinolins in moderate to excellent yield. This reaction proceeded smoothly
to construct CeN and CeP bonds in one-pot with good functional group tolerance under mild conditions.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
2-Alkynylbenzaldoxime
P(O)eH compounds
Silver triflate
Tandem reaction
Isoquinoline
1. Introduction
easily available precursors of dipoles in 1,3-dipolar cycloaddition
reactions, reacted with ketenes to afford the isoquinolin-1-yl
Aromatic organophosphorus compounds are an extremely im-
portant class of chemicals, which have recently received significant
attention due to their extensive application in medicinal chemis-
try,1 materials science,2 and organic synthesis.3 Among these
compounds, arylphosphine oxides exhibit prime applications as
ligands in catalytic chemistry,4 and as metal extractants.5 There-
fore, the development of new methodologies for the introduction of
phosphorus-containing groups into organic compounds has be-
come the subject of intensive research.6 Recently, tremendous
progress has been made in the development of a transition metal
catalyzed reaction of aryl halides,7 triflates,8a imidazolylsulfonat,8b
dizaonium salts,8c boronic acids,8d-f and triarylbismuths8g with H-
phosphonates for the construction of Csp2 eP bond. However, these
methods suffer from relatively strict reaction condition or poor
substrate scope in most cases. Therefore, the development of effi-
cient and complementary methods for Csp2 eP bond formation is
still highly desirable.
2-arylacetates.9h Moreover, 1-aroxyisoquinolines can be readily
prepared by reaction of 2-alkynylbenzaldoximes and phenols.9i
In the process, isoquinoline N-oxide in situ derived from 2-
alkynylbenzaldoxime via 6-endo cyclization in the presence of
a catalytic amount of a Lewis acid was identified as the key in-
termediate, which would proceed furthercyclization or nucleophilic
addition. In the meantime, recent studies have revealed that the
presence of phosphorus-containing substituents can impart favor-
able properties to heterocycles.11 Encouraged by aforementioned
results, we envisioned that 1-phosphorylated isoquinolines could be
produced through the tandem reaction of 2-alkynylbenzaldoxime
with H-phosphonates. Herein, we would like to disclose our work
on the direct and efficient synthesis of 1-phosphorylated iso-
quinolins through silver(I)-catalyzed tandem reaction of 2-
alkynylbenzaldoximes 1 with P(O)eH compounds 2 involving CeN
and CeP bond formation.
Recently, 2-alkynylbenzaldoxime has continuously drawn at-
tention as a versatile building block in tandem reactions for the
preparation of isoquinoline derivatives.9,10 Along these lines, we
have disclosed that 2-alkynylbenzaldoximes can be used as
2. Results and discussion
At the beginning of this study, the reaction of 2-(phenylethynyl)
benzaldehyde oxime 1a with diphenylphosphine oxide 2a was ex-
amined (Table 1). In the presence of 10 mol % silver triflate in ace-
tonitrile, the tandem reaction proceeded smoothly at 80 ꢀC to afford
the desired product 1-(diphenylphosphoryl)-3-phenylisoquinoline
* Corresponding author. Tel./fax: þ86 23 65102531; e-mail address: zwang@cqu.
edu.cn (Z. Wang).
http://dx.doi.org/10.1016/j.tet.2014.06.060
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

X. Wang, Z. Wang / Tetrahedron 70 (2014) 5720e5724
5721
Table 1
additives (entries 13e20). Gratifyingly, the optimized yield 73% was
obtained in the presence of 4 A molecular sieve (MS) as an additive
Optimization of the reaction conditionsa
ꢀ
(entry 21). Reducing the amount of reactant 2a from 1.5 equiv to
1.1 equiv resulted in a slightly lower yield (64%, entry 23). No im-
provement was observed when the amount of 2a was increased to
3.0 equiv (73%, entry 24).
With the optimized reaction conditions in hand, we then ex-
amined the substrate scope of this tandem reaction. The results are
summarized in Table 2. Reactions of diphenylphosphine oxide 2a
with various 2-alkynylbenzaldoxime 1 were evaluated first. For
most cases, the reactionworked well to furnish the desired products
3 in fair to good yields (Table 2). It was found that higher yields were
obtained when electron-rich groups were located on the aromatic
backbone of the 2-alkynylbenzaldoxime 1 than electron-deficient
groups in this tandem reaction (entries 2e6). On the other hand,
with respect to the alkyne portion of the 2-alkynylbenzaldoxime 1,
the reaction tolerated electron-deficient and-rich aryl and alkyl
groups on the R2 position, affording the corresponding products in
yields ranging from 53% to 81% (entries 7e13). However, only a trace
amount of product was detected when 2-(phenylethynyl)nic-
otinaldehyde oxime 1n was utilized in reaction of diphenylphos-
phine oxide 2a (entry 14). Furthermore, we showed that H-
phosphonate diesters are also suitable partners for this trans-
formation. For instance, diethyl H-phosphonate 2b gave 3o in
moderate yield, while its isopropyl analogue 2c afforded the desired
product 3p in a lower yield (entries 15 and 16). In addition, di-p-
tolylphosphine oxide 2d and bis(3,5-dimethylphenyl)phosphine
oxide 2e were also used as the reactants, gave the corresponding
products 3q and 3r in 68% and 64% yields, respectively (entries 17
and 18).
Entry
Solvent
T (ꢀC)
Additive
Yieldb (%)
1
2
3
4
5
6
7
8
CH3CN
CH3CN
CH3CN
CH3CN
THF
1,4-Dioxane
DMF
Toluene
DCE
80
60
40
25
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
40
d
40
45
46
42
52
63
30
43
47
45
23
52
25
40
60
59
24
47
47
50
73
66
64
73
d
d
d
d
d
d
d
9
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23c
24d
DCM
EtOH
DMSO
d
d
d
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-DIOXANE
1,4-Dioxane
Na2CO3
Et3N
t-BuOK
Pyridine
i-Pr2EtN
K3PO4
TsCl
PyBroP
ꢀ
4 A MS
Na2SO4
ꢀ
4 A MS
ꢀ
4 A MS
a
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), solvent (2.0 mL), AgOTf
(0.02 mmol), additive (2.0 equiv).
b
Table 2
Substrates scope
Isolated yields based on 2-(phenylethynyl)benzaldehyde oxime 1a.
Diphenylphosphine oxide 2a of 1.1 equiv was used.
c
d
Diphenylphosphine oxide 2a of 3.0 equiv was used.
3a in moderate yield (40%, entry 1). The structure of compound 3a
was unambiguously demonstrated by X-ray diffraction analysis
(Fig. 1). Motivated by this result, we further optimized the tandem
reaction by varying the reaction temperature, solvent and additive.
Temperature screening led to identification of 40 ꢀC as the best
choice for the transformation (entry 3). Various solvents were sur-
veyed next, revealing that 1,4-dioxane is best suited to run this re-
action to provide 3a in 63% yield (entry 6). Other solvents including
THF, DMF, toluene, DCE, DMF, ethanol, and DMSO were less effective
(entries 5e12). We next turned our attention to further improve
the yield of 3a by investigating the effect of additives. We found
that the yield could not be improved by using various bases, TsCl
or tri(pyrrolidino)phosphonium hexafluorophosphate (PyBroP) as
Entry
R1, R2 (1)
R3 (2)
Yielda (%)
1
2
3
4
5
6
7
8
H, C6H5 (1a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
C6H5 (2a)
73 (3a)
87 (3b)
90 (3c)
76 (3d)
71 (3e)
56 (3f)
72 (3g)
70 (3h)
81 (3i)
75 (3j)
53 (3k)
71 (3l)
81 (3m)
5-Me, C6H5 (1b)
4,5-OMe, C6H5 (1c)
5-Cl, C6H5 (1d)
5-F, C6H5 (1e)
4-F, C6H5 (1f)
H, p-ClC6H4 (1g)
H, p-MeOC6H4 (1h)
H, p-EtO2CC6H4 (1i)
H, c-Pr (1j)
9
10
11
12
13
5-F, c-Pr (1k)
5-F, n-Bu (1l)
H, t-Bu (1m)
14
C6H5 (2a)
Trace (3n)
15b
16b
17
H, C6H5 (1a)
H, C6H5 (1a)
H, C6H5 (1a)
H, C6H5 (1a)
OEt (2b)
60 (3o)
45 (3p)
68 (3q)
64 (3r)
OiPr (2c)
4-MeC6H4 (2d)
3,5-Me2C6H3 (2e)
18
a
Isolated yields based on 2-alkynylbenzaldoxime 1.
b
At 80 ꢀC.
It has been reported that P-centered radicals can be formed from
diarylphosphine oxides with Ag-based oxidants.6fei To further de-
termine whether the reaction proceeded via a radical process, we
included 3 equiv of TEMPO, a radical trap in the model tandem
Fig. 1. X-ray ORTEP illustration of 3a (30% probability ellipsoids).

5722
X. Wang, Z. Wang / Tetrahedron 70 (2014) 5720e5724
reaction. No TEMPO-trapped compound 2a0 was detected and the
desired product 3a was formed in 30% yield (Scheme 1). This result
indicated a radical pathway is less likely in this transformation. On
the basis of this experimental result and previous reports,11beg
we proposed a possible mechanism of this reaction outlined in
Scheme 2. Initially, as mentioned above, the presence of silver
would promote the 6-endo cyclization of 2-alkynylbenzaldoxime 1
to generate isoquinoline N-oxide B. Subsequently, the tautomer A of
2 as a nucleophile would attack isoquinoline N-oxide B to afford the
intermediate C. Finally, the intermediate C would undergo a proton
transfer and rearomatization of D would occur to furnish the cor-
responding product 3.
4.2. General procedure for the synthesis of 3
A mixture of silver triflate (0.02 mmol, 5.1 mg) and 2-
alkynylbenzaldoxime 1 (0.2 mmol) in 1,4-dioxane (1.0 mL) was
stirred at 70 ꢀC under N2 for 2 h. P(O)eH 2 (0.3 mmol), 4 A MS
ꢀ
(100 mg), and 1, 4-dioxane (1.0 mL) were added subsequently. The
reaction mixture was stirred at 40 ꢀC until completion of the re-
action as indicated by TLC. Evaporation of the solvent followed by
purification on silica gel afforded the corresponding product 3.
4.2.1. 1-(Diphenylphosphoryl)-3-phenylisoquinoline (3a). White solꢁid1;
mp 180.2e181.1 ꢀC; IR (neat) 3057, 1588, 1551, 1497, 1452, 1188 cm
;
1H NMR (400 MHz, CDCl3)
d 7.34e7.41 (m, 3H), 7.42e7.48 (m, 4H),
7.53 (t, J¼7.2 Hz, 2H), 7.59 (t, J¼7.4 Hz, 1H), 7.68 (t, J¼7.3 Hz, 1H),
7.86e7.91 (m, 7H), 8.17 (d, J¼2.0 Hz, 1H), 9.31 (d, J¼8.5 Hz, 1H); 13C
NMR (100 MHz, CDCl3)
d 118.3, 126.6, 127.2, 127.8, 128.2 (d,
JPC¼11.8 Hz), 128.8 (d, JPC¼8.5 Hz), 130.4, 130.6, 131.3 (d, JPC¼97.9 Hz),
132.3 (d, JPC¼9.2 Hz), 133.3, 137.2, 137.3, 138.4, 148.9, 149.2, 155.9; 31
P
NMR (162 MHz, CDCl3) d 29.48 (s); HRMS (ESI) calcd for C27H20NOP:
406.1355 (MþHþ), found: 406.1384.
Scheme 1. Mechanical experiment.
Crystallographic data for the structure 3a have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 993924. Copies of the data can be obtained free
of charge on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK [fax: þ44 1223 336 033; e-mail: deposit@ccdc.cam.ac.uk].
4.2.2. 1-(Diphenylphosphoryl)-7-methyl-3-phenylisoquinoline
(3b). White solid; mp 163.5e164.2 ꢀC; IR (neat) 3055, 2918, 2849,
1588, 1546, 1502, 1414, 1187 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 2.50
(s, 3H), 7.33e7.40 (m, 3H), 7.44e7.49 (m, 7H), 7.77 (d, J¼8.2 Hz, 2H),
7.88 (t, J¼6.3 Hz, 7H), 8.10 (s, J¼1H), 9.13 (s, 1H); 13C NMR (100 MHz,
CDCl3)
d
22.3, 118.2, 125.8, 126.5, 127.6,128.2 (d, JPC¼12.0 Hz), 128.7 (d,
JPC¼7.7 Hz), 130.8, 131.7, 132.4 (d, JPC¼9.2 Hz), 133.1 (d, JPC¼104.1 Hz),
133.2, 135.6 (d, JPC¼7.1 Hz), 138.5, 148.2, 148.4, 153.5, 154.8; 31P NMR
(162 MHz, CDCl3)
d 29.21 (s); HRMS (ESI) calcd for C28H22NOP:
420.1512 (MþHþ), found: 420.1523.
4.2.3. 1-(Diphenylphosphoryl)-6,7-dimethoxy-3-phenylisoquinoline
Scheme 2. Proposed reaction mechanism.
(3c). White solid; mp 167.3e168.1 ꢀC; IR (neat) 3057, 2958, 2840,
1589, 1557, 1504, 1468, 1437, 1337, 1160 cmꢁ1 1H NMR (400 MHz,
;
3. Conclusion
CDCl3)
d 4.01 (s, 6H), 7.12 (s,1H), 7.37e7.50 (m, 7H), 7.67e7.72 (m, 2H),
7.89e7.95 (m, 6H), 8.03 (s, 1H), 8.84 (s, 1H); 13C NMR (100 MHz, CDCl3)
In summary, we have developed a facile approach to the syn-
thesis of 1-phosphorylated isoquinolins starting from readily ac-
cessible 2-alkynylbenzaldoxime and commercially available H-
phosphine oxides, and H-phosphinate esters. The reaction proceeds
smoothly to provide the corresponding products in moderate to
excellent yields. This methodology will serve as an important tool
for the efficient synthesis of a variety of useful 1-phosphonylated
isoquinolines, which can be used as remarkably versatile building
blocks for further biological screening and medical application.
d
56.0, 56.3,105.1,105.3,117.2,126.4,128.2 (d, JPC¼12.0 Hz),128.5,128.7,
128.9 (d, JPC¼12.8 Hz), 130.7 (d, JPC¼11.4 Hz), 132.1 (d, JPC¼98.5 Hz),
132.4 (d, JPC¼9.1 Hz), 133.8, 134.5 (d, JPC¼7.5 Hz), 138.8, 150.8 (d,
JPC¼14.8 Hz), 152.2, 153.2; 31P NMR (162 MHz, CDCl3)
d 28.39 (s);
HRMS (ESI) calcd for C29H24NO3P: 466.1567 (MþHþ), found: 466.1575.
4.2.4. 7-Chloro-1-(diphenylphosphoryl)-3-phenylisoquinoline
(3d). White solid; mp 182.6e183.4 ꢀC; IR (neat) 3055, 1585, 1544,
1475, 1435, 1106 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.39 (d, J¼7.4 Hz,
3H), 7.46 (d, J¼5.5 Hz, 4H), 7.52 (d, J¼6.8 Hz, 2H), 7.59 (d, J¼8.5 Hz,
1H), 7.81 (d, J¼8.6 Hz,1H), 7.87e7.93 (m, 6H), 8.01 (s,1H), 9.49 (s,1H);
4. Experimental
4.1. General
13C NMR (100 MHz, CDCl3)
d
117.9,126.1, 126.6,128.3 (d, JPC¼12.1 Hz),
128.9, 129.1 (d, JPC¼13.0 Hz), 131.1, 131.3 (d, JPC¼105.1 Hz), 132.0, 132.3
(d, JPC¼9.2 Hz), 133.3, 133.9, 135.5 (d, JPC¼6.8 Hz), 138.0, 149.4, 149.6,
NMR spectra were recorded with a Bruker DRX-400 spectrom-
eter (400 MHz for 1H, 100 for 13C, 162 MHz for 31P, and 378 MHz for
19F) with CDCl3 as a solvent at 20e25 ꢀC. High-resolution mass
spectra (HRMS) were recorded on a micrOTOF II MS spectrometer.
IR spectra were recorded on a Shimidazu IR-400 spectrometer and
wave number was reported in unit of cmꢁ1. Unless otherwise
stated, all commercial materials were used without further purifi-
cation. All solvents were dried and distilled according to standard
procedures. Column chromatography was performed using silica
gel (300e400 mesh).
154.0, 155.2; 31P NMR (162 MHz, CDCl3)
d 29.48 (s); HRMS (ESI) calcd
for C27H19ClNOP: 440.0966 (MþHþ), found: 440.0979.
4.2.5. 1-(Diphenylphosphoryl)-7-fluoro-3-phenylisoquinoline
(3e). White solid; mp 160.4e161.1 ꢀC; IR (neat) 3058, 1624, 1587,
1502, 1450, 1188 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 7.37e7.41 (m,
3H), 7.44e7.48 (m, 5H), 7.53 (t, J¼7.4 Hz, 2H), 7.88e7.93 (m, 7H), 8.14
(d, J¼2.0 Hz, 1H), 9.11e9.14 (m, 1H); 13C NMR (100 MHz, CDCl3)
2
2
d
111.0 (d, JCF¼23.2 Hz), 118.0, 121.8 (d, JCF¼26.0 Hz), 128.3 (d,
JPC¼12.1 Hz),128.8 (d, JPC¼10.4 Hz),130.2 (d, JPC¼8.6 Hz),132.4,132.8

X. Wang, Z. Wang / Tetrahedron 70 (2014) 5720e5724
5723
(d, JPC¼98.5 Hz), 134.4 (d, JPC¼6.9 Hz), 138.2, 148.8, 149.0, 154.0,
7.72e7.81 (m, 5H), 9.02e9.05 (m, 1H); 13C NMR (100 MHz, CDCl3)
155.4, 161.5 (d, 1JCF¼249.7 Hz); 31P NMR (162 MHz, CDCl3)
d
28.35
d
9.8, 16.5, 110.6 (d, JCF¼23.0 Hz), 119.5, 121.5 (d, JCF¼26.2 Hz), 128.1
(s); 19F NMR (378 MHz, CDCl3)
C
d
ꢁ107.9 (s); HRMS (ESI) calcd for
(d, JPC¼12.1 Hz), 128.8 (d, JPC¼8.3 Hz), 131.7, 132.2 (d, JPC¼9.2 Hz),
132.9 (d, JPC¼104.5 Hz), 133.9 (d, JPC¼7.2 Hz), 154.3, 154.5, 159.7 (d,
27H19FNOP: 424.1261 (MþHþ), found: 424.1270.
JCF¼247.2 Hz); 31P NMR (162 MHz, CDCl3)
d
28.42 (s); 19F NMR
4.2.6. 1-(Diphenylphosphoryl)-6-fluoro-3-phenylisoquinoline
(3f). White solid; mp 211.5e212.2 ꢀC; IR (neat) 3060, 1591, 1555, 1491,
(378 MHz, CDCl3)
d
ꢁ110.1 (s); HRMS (ESI) calcd for C24H19FNOP:
410.1081 (MþNaþ), found: 410.1071.
1454, 1116 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 7.32e7.41 (m, 4H),
7.43e7.55 (m, 7H), 7.87e7.92 (m, 6H), 8.10 (d, J¼2.0 Hz, 1H), 9.46e9.50
4.2.12. 3-Butyl-1-(diphenylphosphoryl)-7-fluoroisoquinoline (3l). White
solid; mp 148.8e149.7 ꢀC; IR (neat) 3083, 3060, 2950, 2922, 2867,
(m, 1H); 13C NMR (100 MHz, CDCl3)
d
110.8 (d, 2JCF¼20.9), 117.7, 118.6
2
(d, JCF¼25.0), 126.7, 127.7, 127.9, 128.2 (d, JPC¼12.1 Hz), 128.8, 129.2,
130.7, 131.3 (d, JPC¼109.7 Hz), 132.3 (d, JPC¼9.3 Hz), 133.3, 138.0, 139.2,
2856, 1627, 1587, 1481, 1457, 1341, 1180 cmꢁ1 1H NMR (400 MHz,
;
CDCl3)
d
0.85 (t, J¼7.3 Hz, 3H), 1.19e1.28 (m, 2H), 1.61e1.69 (m, 2H), 2.86
2
149.8, 150.0, 154.9, 156.2, 163.8 (d, JCF¼253.1); 31P NMR (162 MHz,
(t, J¼7.4 Hz, 2H), 7.38e7.45 (m, 5H), 7.47e7.49 (m, 3H), 7.75 (t, J¼7.8 Hz,
CDCl3)
d
28.76 (s); 19F NMR (378 MHz, CDCl3)
d
ꢁ106.4 (s); HRMS (ESI)
1H), 7.88e7.93 (m, 4H), 9.18e9.21 (m, 1H); 13C NMR (100 MHz, CDCl3)
calcd for C27H29FNOP: 424.1261 (MþHþ), found: 424.1258.
d
14.0, 22.1, 31.4, 37.0,110.5 (d, JCF¼23.1 Hz),120.5,121.3 (d, JCF¼26.1 Hz),
128.1 (d, JPC¼12.0 Hz), 129.2 (d, JPC¼8.5 Hz),130.4 (d, JPC¼10.2 Hz), 130.7
(d, JPC¼10.3 Hz), 132.0 (d, JPC¼100.9 Hz), 132.4 (d, JPC¼9.1 Hz), 133.7,
134.2 (d, JPC¼7.4 Hz), 153.9, 154.1, 160.5 (d, JCF¼160.5 Hz); 31P NMR
4.2.7. 3-(4-Chlorophenyl)-1-(diphenylphosphoryl)isoquinoline
(3g). White solid; mp 206.6e207.3 ꢀC; IR (neat) 3056, 1595, 1551,
1483, 1437, 1119 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
7.34 (d, J¼8.3 Hz,
(162 MHz, CDCl3)
d
26.54 (s); 19F NMR (378 MHz, CDCl3)
d
ꢁ108.8 (s);
2H), 7.45e7.47 (m, 4H), 7.51e7.59 (m, 3H), 7.66 (t, J¼7.1 Hz, 1H), 7.78
HRMS (ESI) calcd for C25H23FNOP: 426.1394 (MþNaþ), found: 426.1410.
(t, J¼8.3 Hz, 2H), 7.84e7.89 (m, 5H), 8.10 (s, 1H), 9.29 (d, J¼8.6 Hz,
1H); 13C NMR (100 MHz, CDCl3)
d
118.2, 127.3, 127.8 (d, JPC¼7.3 Hz),
4.2.13. 3-tert-Butyl-1-(diphenylphosphoryl)isoquinoline (3m). White
solid; mp 178.8e179.2 ꢀC; IR (neat) 3057, 2956, 2864, 1580, 1552,
128.2 (d, JPC¼12.2 Hz), 128.9, 131.5 (d, JPC¼86.9 Hz), 132.3 (d,
JPC¼9.2 Hz),134.3 (d, JPC¼152.5 Hz),136.9,137.1 (d, JPC¼7.0 Hz),147.8,
1480, 1461, 1437, 1336, 1188 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d 1.26
148.0, 155.1, 156.4; 31P NMR (162 MHz, CDCl3)
d
29.32 (s); HRMS
(s, 9H), 7.41e7.45 (m, 4H), 7.48e7.56 (m, 3H), 7.62e7.65 (m, 2H),
(ESI) calcd for C27H19ClNOP: 440.0966 (MþHþ), found: 440.0960.
7.80e7.87 (m, 5H), 9.32 (d, J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
29.9, 37.3, 116.8, 126.9, 127.3 (d, JPC¼8.4 Hz), 128.0(d, JPC¼11.9 Hz),
4.2.8. 1-(Diphenylphosphoryl)-3-(4-methoxyphenyl)isoquinoline
130.3, 131.5, 132.2 (d, JPC¼9.1 Hz), 133.3 (d, JPC¼104.5 Hz), 137.0 (d,
(3h). White solid; mp 181.8e182.5 ꢀC; IR (neat) 3055, 2933, 2835,1607,
JPC¼6.9 Hz), 153.6, 154.9; 31P NMR (162 MHz, CDCl3)
d 28.86 (s);
1551, 1514, 1483, 1437, 1368, 1182 cmꢁ1
;
1H NMR (400 MHz, CDCl3)
HRMS (ESI) calcd for C25H24NOP: 386.1668 (MþHþ), found: 386.1669.
d
3.83 (s, 3H), 6.91 (d, J¼8.6 Hz, 2H), 7.45e7.46 (m, 4H), 7.51e7.55 (m,
3H), 7.64 (t, J¼7.0 Hz, 1H), 7.81e7.91 (m, 7H), 8.06 (s, 1H), 9.29 (d,
4.2.14. Diethyl 3-phenylisoquinolin-1-ylphosphonate (3o). White
solid; mp 90.6e91.1 ꢀC; IR (neat) 3065, 2982, 2850,1589,1557,1497.8,
J¼8.2 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d 55.4, 114.2, 117.1, 127.2,
127.6, 127.7, 127.9, 128.2 (d, JPC¼12.0 Hz), 130.6 (d, JPC¼106.1 Hz), 131.2
(d, JPC¼101.2 Hz), 132.3 (d, JPC¼9.2 Hz), 133.1 (d, JPC¼104.5 Hz), 137.3,
1452, 1368, 1245 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.42 (t, J¼7.0 Hz,
6H), 4.35e4.46 (m, 4H), 7.43 (t, J¼7.0 Hz, 1H), 7.52 (t, J¼7.3 Hz, 2H),
7.66 (t, J¼7.8 Hz, 1H), 7.72 (t, J¼6.9 Hz, 1H), 7.91 (t, J¼7.6 Hz, 1H), 8.18
(t, J¼7.7 Hz, 3H), 8.92 (d, J¼8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3)
148.8, 149.0, 154.5, 155.8, 160.4; 31P NMR (162 MHz, CDCl3)
d 29.16 (s);
HRMS (ESI) calcd for C28H22NO2P: 436.1461 (MþHþ), found: 436.1471.
d
16.4, 16.5, 63.5, 63.6, 119.3, 126.9, 127.1, 127.7, 128.2, 128.9, 130.7,
4.2.9. Ethyl
(3i). White solid; mp 217.5e218.3 ꢀC; IR (neat) 3057, 2929, 2852,
1609, 1552, 1510, 1437, 1365, 1187 cmꢁ1 1H NMR (400 MHz, CDCl3)
4-(1-(diphenylphosphoryl)isoquinolin-3-yl)benzoate
137.1 (d, JPC¼10.7 Hz), 138.7, 149.8, 150.0, 151.3, 153.5; 31P NMR
(162 MHz, CDCl3)
d 10.05 (s); HRMS (ESI) calcd for C19H20NO3P:
;
342.1254 (MþHþ), found: 342.1270.
d
1.41 (t, J¼7.1 Hz, 3H), 4.37e4.42 (m, 2H), 7.47e7.48 (m, 4H), 7.55 (t,
J¼7.1 Hz, 2H), 7.61 (t, J¼7.8 Hz,1H), 7.70 (t, J¼7.2 Hz,1H), 7.86e7.94 (m,
4.2.15. Diisopropyl 3ꢀ-phenylisoquinolin-1-ylphosphonate (3p). White
7H), 8.06 (d, J¼8.2 Hz, 2H), 8.22 (s,1H), 9.32 (d, J¼4.4 Hz,1H); 13C NMR
solid; mp 78.9e79.4 C; IR (neat) 3059, 2978, 2856, 1626, 1556, 1500,
(100 MHz, CDCl3)
d
14.4, 61.1, 119.2, 127.4, 127.9, 128.2 (d, JPC¼12.1 Hz),
1452, 1377, 1242 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
1.41 (d, J¼6.1 Hz,
128.7, 130.4, 130.6 (d, JPC¼101.3 Hz), 133.2 (d, JPC¼9.2 Hz), 132.3 (d,
12H), 4.92e5.01 (m, 2H), 7.43 (t, J¼7.3 Hz, 1H), 7.52 (t, J¼7.3 Hz, 2H),
7.65e7.72 (m, 2H), 7.91 (d, J¼8.1 Hz,1H), 8.19 (d, J¼6.7 Hz, 3H), 8.98 (d,
JPC¼104.8 Hz), 137.0, 137.1, 142.5, 147.7, 147.9, 155.3, 155.6, 166.4; 31P
NMR (162 MHz, CDCl3)
d
29.29 (s); HRMS (ESI) calcd for C30H24NO3P:
J¼8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
24.0 (d, JPC¼5.2 Hz), 24.1
478.1567 (MþHþ), found: 478.1592.
(d, JPC¼2.9 Hz), 72.3 (d, JPC¼6.0 Hz), 119.2, 127.1, 127.4, 127.7, 128.0,
128.7, 130.5, 138.9, 154.5; 31P NMR (162 MHz, CDCl3)
d 8.29 (s); HRMS
4.2.10. 3-Cyclopropyl-1-(diphenylphosphoryl)isoquinoline (3j). White
solid; mp 158.6e159.3 ꢀC; IR (neat) 3053, 2918, 2849, 1585, 1552,
(ESI) calcd for C21H24NO3P: 392.1386 (MþNaþ), found: 392.1391.
1482, 1454, 1368, 1188 cmꢁ1; 1H NMR (400 MHz, CDCl3)
d
0.69e0.72
4.2.16. 1-(Dip-tolylphosphoryl)-3-phenylisoquinoline(3q). White solid;
mp 168.7e169.3 ꢀC; IR (neat) 3055, 2920, 2859, 1601, 1552, 1497, 1452,
(m, 2H), 0.83e0.86 (m, 2H), 2.03e2.09 (m, 1H), 7.41e7.45 (m, 4H),
7.47e7.52 (m, 3H), 7.59e7.63 (m, 2H), 7.73e7.80 (m, 5H), 9.26 (d,
1366, 1183 cmꢁ1 1H NMR (400 MHz, CDCl3)
; d 2.37 (s, 6H), 7.25 (d,
J¼8.5 Hz, 1H); 13C NMR (100 MHz, CDCl3)
d
9.7, 16.7, 119.7, 126.4,
J¼5.7 Hz, 4H), 7.34e7.42 (m, 3H), 7.56 (t, J¼7.6 Hz, 1H), 7.66 (t,
J¼7.2 Hz, 1H), 7.75e7.80 (m, 4H), 7.87 (d, J¼8.2 Hz, 1H), 7.92 (d,
J¼7.0 Hz, 2H), 8.14 (d, J¼2.0 Hz, 1H), 9.34 (d, J¼8.5 Hz, 1H); 13C NMR
126.9, 127.1, 128.1 (d, JPC¼12.0 Hz), 129.8, 131.0 (d, JPC¼109.2 Hz),
132.1 (d, JPC¼9.2 Hz), 133.1 (d, JPC¼104.7 Hz), 136.8 (d, JPC¼7.5 Hz),
154.5, 154.7, 155.4; 31P NMR (162 MHz, CDCl3)
d
29.06 (s); HRMS
(100 MHz, CDCl3) d 21.6, 118.1, 126.7, 127.4, 127.7, 128.0, 128.8, 128.9 (d,
(ESI) calcd for C24H20NOP: 392.1175 (MþNaþ), found: 392.1192.
JPC¼12.7 Hz), 130.0 (d, JPC¼107.2 Hz), 130.6 (d, JPC¼11.3 Hz), 132.3 (d,
JPC¼9.9 Hz), 137.2 (d, JPC¼7.0 Hz), 138.5, 142.1, 148.9, 149.1, 155.2, 156.5;
4.2.11. 3-Cyclopropyl-1-(diphenylphosphoryl)-7-fluoroisoquinoline
(3k). White solid; mp 182.5e183.1 ꢀC; IR (neat) 3059, 2920, 2847,
1585, 1560, 1493, 1437, 1380, 1190 cmꢁ1; 1H NMR (400 MHz, CDCl3)
31P NMR (162 MHz, CDCl3)
d 29.41 (s); HRMS (ESI) calcd for
C
29H24NOP: 434.1668 (MþHþ), found: 434.1698.
d
0.70e0.74 (m, 2H), 0.85e0.89 (m, 2H), 2.02e2.08 (m, 1H),
4.2.17. 1-(Bis(3,5-dimethylphenyl)phosphoryl)-3-phenylisoquinoline
(3r). White solid; mp 166.6e167.4 ꢀC; IR (neat) 3036, 2919, 2857,
7.37e7.45 (m, 5H), 7.51 (t, J¼7.3 Hz, 2H), 7.58 (d, J¼2.0 Hz, 1H),

5724
X. Wang, Z. Wang / Tetrahedron 70 (2014) 5720e5724
Hoboken, NJ, 2000; (d) Bhattacharta, A. K.; Thyagarajan, G. Chem. Rev. 1981, 81,
1588, 1551, 1497, 1452, 1365, 1185 cmꢁ1
;
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Tang, W.; Zhang, X. Chem. Rev. 2003, 103, 3029.
d
2.31 (s, 12H), 7.14 (s, 2H), 7.37e7.44 (m, 3H), 7.52 (d, J¼8.4 Hz, 4H),
7.58 (t, J¼7.7 Hz, 1H), 7.67 (t, J¼7.0 Hz,1H), 7.89 (d, J¼8.0 Hz, 1H), 7.98
4. (a) Shaikh, T. M.; Weng, C.-M.; Hong, F.-E. Coord. Chem. Rev. 2012, 256, 771; (b)
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(100 MHz, CDCl3)
d 21.3, 118.1, 126.7, 127.4, 127.7, 128.1, 128.8 (d,
JPC¼5.8 Hz), 129.9 (d, JPC¼9.1 Hz), 130.7, 132.7 (d, JPC¼103.2 Hz), 133.5,
137.2 (d, JPC¼6.5 Hz), 137.7 (d, JPC¼12.6 Hz), 138.6, 148.8, 149.0, 154.9,
156.2; 31P NMR (162 MHz, CDCl3)
d 29.33 (s); HRMS (ESI) calcd for
C
31H28NOP: 462.1981 (MþHþ), found: 462.1993.
Acknowledgements
We thank Professor Jie Wu for his invaluable advice during the
course of this research. Financial support from National Natural
Science Foundation of China (No. 21302236), Fundamental Research
Funds for the Central Universities (CDJRC11220001, CQDXWl-2013-
023) and the Scientific Research Foundation for the Returned
Overseas Chinese Scholars, State Education Ministry (No. [2013]693)
is gratefully acknowledged.
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Supplementary data
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