Palladium-catalyzed intramolecular direct arylation for phosphorus heterocycle synthesis

Article abstract of DOI:10.1055/s-0033-1340832

A palladium-catalyzed intramolecular direct arylation of bromo-substituted phosphine oxides is reported for the synthesis of phosphorus-containing heterocycles with good to excellent yields (78-98%). Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1340832

PAPER
▌1067
paper
Palladium-Catalyzed Intramolecular Direct Arylation for Phosphorus
Heterocycle Synthesis
Phosphorus Heterocycle Synthesis
Yun-Rong Chen, Wei-Liang Duan*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road,
Shanghai 200032, P. R. of China
Fax +86(21)64166128; E-mail: wlduan@mail.sioc.ac.cn
Received: 06.12.2013; Accepted after revision: 27.01.2014
tive yield as that obtained with the combination of simple
Abstract: A palladium-catalyzed intramolecular direct arylation of
triphenylphosphine as the ligand and potassium carbonate
bromo-substituted phosphine oxides is reported for the synthesis of
as the base (entry 18).
phosphorus-containing heterocycles with good to excellent yields
(78–98%)
With the optimum conditions determined, the scope of
Key words: C–H activation, direct arylation, palladium, phospho- substrates was explored; the results are shown in Scheme
rus heterocycles
1. Substrates bearing either electron-rich or electron-poor
groups, such as methoxy, alkyl, and halide groups, can be
employed to afford the corresponding products in high
yields. More sterically hindered substrates require higher
temperature (130 °C) to achieve high conversion (2j and
2k). Attempts to develop an asymmetric variant of the
current reaction remain unsuccessful. Various chiral li-
gands, such as mono- or bisphosphine, phosphoramidate,
and N-heterocyclic carbene,8 were examined, but the
products were always isolated in racemic form (Scheme
2), which may be attributed to the high flexibility of the
carbon linker of substrate 1c.
Transition-metal-catalyzed C–H bond activation reac-
tions have gained considerable attention over the past de-
cades because these processes do not require substrates
bearing functionalized groups. Numerous methods have
been developed for the synthesis of complex molecules
from simple materials, which include various nitrogen-
and oxygen-containing heterocycles.1,2 In contrast, appli-
cation of C–H activation strategies to the synthesis of
phosphorus heterocycles has rarely been investigated, al-
though phosphorus compounds are widely used materials
in various fields, such as catalysis, pharmaceuticals, ag-
richemicals, and material chemistry.3 Examples based on
C–H bond activation strategies with palladium, rutheni-
um, or rhodium catalysts have only recently been reported
for the construction of phosphorus-containing heterocy-
cles.4,5 In this paper, we describe a palladium-catalyzed
intramolecular direct arylation reaction for the synthesis
of phosphorus heterocycles with high yield.6
Competition experiments with substrates bearing differ-
ent moieties were conducted, and the results show that
electron-deficient substrates have higher reactivity than
electron-rich substrates (Scheme 3), which is consistent
with the phenomenon observed in the concerted metala-
tion–deprotonation (CMD) pathway.9 On this basis, a pro-
posed mechanism for the current reaction is shown in
Scheme 4. Oxidative addition of the aryl bromide bond to
palladium(0) initially occurs to generate a palladium(II)
aryl intermediate. The bromide is then replaced by a piv-
alate anion, followed by an intramolecular CMD step, af-
fording intermediate C. Finally, reductive elimination of
C from the palladium(II) atom releases the coupling prod-
uct and regenerates the palladium(0) active catalyst
(Scheme 4).
Initially, we chose ortho-bromophenyl diphenylphosphi-
nate (1a) as the starting material. The expected coupled
product could be easily converted into a diverse range of
phosphorus compounds.7 Palladium acetate was used as
the metal catalyst for the current reaction. After screening
various reaction parameters, including solvents, ligands,
and bases (Table 1, entries 1–16), the highest product
yield was 54% (entry 16), which occurred with complete
consumption of 1a. The possible reason for this moderate
yield may be the decomposition of substrate 1a under the
reaction conditions. We then investigated the use of alter-
native substrates for the current reaction. Substrate 1b,
with one more carbon atom than 1a, did not produce the
corresponding arylation product (entry 17). In contrast,
with the oxygen atom in 1a replaced by a carbon atom,
substrate 1c was found to be a good candidate, yielding
the desired product with approximately the same quantita-
In conclusion, a palladium-catalyzed intramolecular di-
rect arylation of bromo-substituted phosphine oxides was
developed, yielding six-membered phosphorus heterocy-
cles in high yields.
Commercially available reagents were used without further purifi-
cation. Solvents were treated prior to use according to the standard
methods. Melting points were determined using an SGW X-4 melt-
ing point apparatus and are uncorrected. 1H NMR, 13C NMR and 31
P
NMR spectra were recorded at r.t. in CDCl3 with a Varian 400 MHz
spectrometer using tetramethylsilane as internal standard. Flash col-
umn chromatography was performed on silica gel (300–400 mesh).
SYNTHESIS 2014, 46, 1067–1072
Advanced online publication: 18.02.2014
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0
3
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7
8
8
1
1
4
3
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DOI: 10.1055/s-0033-1340832; Art ID: SS-2013-H0792-OP
© Georg Thieme Verlag Stuttgart · New York

1068
Y.-R. Chen, W.-L. Duan
PAPER
Table 1 Effect of Solvents, Bases, and Ligandsa
O
P
Pd(OAc)2 (10 mol%)
ligand (10 mol%)
O
P
Ph
X
Ph
Ph
X
base, solvent, temp
Br
1a: X = O
1b: X = OCH2
1c: X = CH2
2a–c
Entry
Substrate
Ligand
Base
Solvent
Temp (°C)
Time (h)
Yield (%)b
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
Ph3P
L1
K3PO4
K2CO3
Na2CO3
PivOK
AcOK
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMA
55
55
55
55
55
55
55
55
55
55
55
55
55
55
55
55
100
60
8
8
0
43
30
10
0
DMA
3
DMA
8
4
DMA
8
5
DMA
8
6
THF
8
0
7
DCE
8
0
8
DMF
8
9
9
toluene
DMA
8
0
10
11
12
13
14
15
16
17
18
8
11
14
0
L2
DMA
8
L3
DMA
8
t-Bu3P
binap
Ph3P
Ph3P
Ph3P
Ph3P
DMA
8
0
DMA
8
0
toluene/DMA(1:1)
toluene/DMA (1:2)
DMA
8
27
54
0
8
24
20
DMA
98
PCy2
PCy2
PPh2
i-Pr
i-Pr
i-Pr
L2
L1
L3
a Reaction conditions: 1 (0.20 mmol), Pd(OAc)2 (10 mol%), ligand (10 mol%), base (0.60 mmol), solvent (3 mL).
b Isolated yield.
Intramolecular Arylation of Bromo-Substituted Phosphine
Oxides; General Procedure
9,10-Dihydro-9-oxa-10-phenyl-10-phosphaphenanthrene-10-
oxide (2a)
Phosphine oxide (0.20 mmol), palladium acetate (4.5 mg, 0.020
mmol), triphenylphosphine (5.2 mg, 0.020 mmol), and pivalic acid
(6.2 mg, 0.060 mmol) were dissolved in dimethyl acetamide (2 mL)
under a nitrogen atmosphere, and the resulting mixture was stirred
at 100 °C for 12 h. After cooling to r.t., the mixture was filtered over
Celite and concentrated under vacuum. The residue was purified by
silica gel chromatography (CH2Cl2–EtOAc) to recover the product
as a white solid.
Yield: 32.8 mg (54%); white solid; mp 172–174 °C.
FTIR (neat): 3055, 2947, 2885, 1589, 1557, 1473, 1435, 1392,
1312, 1223, 1192, 1154, 1115, 1071, 832, 803, 746, 727, 716, 694
cm−1.
1H NMR (400 MHz, CDCl3): δ = 8.04 (dd, J = 8.0, 4.8 Hz, 1 H),
7.99 (dd, J = 8.0, 1.2 Hz, 1 H), 7.86–7.79 (m, 2 H), 7.68 (t, J =
8.0 Hz, 1 H), 7.63–7.56 (m, 2 H), 7.50–7.36 (m, 4 H), 7.29–7.24
(m, 2 H).
Synthesis 2014, 46, 1067–1072
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PAPER
Phosphorus Heterocycle Synthesis
1069
R1
O
P
Pd(OAc)2 (10 mol%)
Ph3P (10 mol%)
O
Ar
Ar
P
R2
K2CO3 (3.0 equiv)
PivOH (0.3 equiv)
DMA, 100 °C, 12 h
R2
Br
R1
O
O
O
O
Ph
Ph
Ph
Ph
P
P
P
P
Cl
OMe
NO2
2c 98%
2d 78%
2e 93%
2f 98%
O
P
Ph
O
O
O
Ph
Ph
Ph
P
P
F
P
Cl
CF3
2h 98%
2i 85%
Cl
2j 83%a
2g 94%
MeO
O
O
P
O
P
P
MeO
Cl
2k 79%a
2l 95%
2m 80%
Scheme 1 Reaction scope. Reagents and conditions: phosphine oxide (0.20 mmol), Pd(OAc)2 (10 mol%), Ph3P (10 mol%), K2CO3 (0.60
mmol), DMA (3 mL), 100 °C, 12 h; isolated yields given. a Reactions were conducted at 130 °C.
O
Pd(OAc)2 (10 mol%)/L (10 mol%)
[Pd(allyl)Cl]2 (5 mol%) for NHC
O
P
Ph
P
Ph
Ph
K2CO3 (3.0 equiv)
PivOH (0.3 equiv)
DMA, 60 or 140 °C, 12 h
Br
1c
2c
O
O
Ph
Ph
PPh2
OMe
PPh2
PPh2
O
O
P
N
N
N
t-Bu
t-Bu
OTf
48%, 0% ee
(60 °C)
98%, 0% ee
(140 °C)
40%, 0% ee
(60 °C)
95%, 0% ee
(140 °C)
Scheme 2 Investigations with chiral ligands
OMe
MeO
(a)
O
O
P
O
P
Ph Pd(OAc)2 (5 mol%)
Ph3P (5 mol%)
O
Ph
P
P
+
+
Ph
PivOH (30 mol%)
K2CO3 (3.0 equiv)
DMA, 100 °C
30 min
Br
Br
MeO
OMe
Cl
2c 50%
2l 25%
1l
1c
Cl
(b)
O
O
P
O
P
Ph
Ph
Pd(OAc)2 (5 mol%)
Ph3P (5 mol%)
O
P
Ph
P
+
+
PivOH (30 mol%)
K2CO3 (3.0 equiv)
DMA, 100 °C
60 min
Br
Br
Cl
Cl
2c 50%
2m 83%
1m
1c
Scheme 3 Competition experiments
© Georg Thieme Verlag Stuttgart · New York
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Y.-R. Chen, W.-L. Duan
PAPER
13C NMR (100 MHz, CDCl3): δ = 159.5 (d, JC–P = 0.7 Hz), 140.0 (d,
JC–P = 7.3 Hz), 132.9 (d, JC–P = 2.4 Hz), 131.7 (d, JC–P = 2.7 Hz),
Ph
P
O
131.2 (d, JC–P = 101.6 Hz), 130.8 (d, JC–P = 5.8 Hz), 130.7 (d, JC–P
6.6 Hz), 130.6 (d, JC–P = 9.7 Hz), 128.2 (d, JC–P = 12.0 Hz), 127.9
(d, JC–P = 2.7 Hz), 127.2 (d, JC–P = 11.2 Hz), 127.0 (d, JC–P
100.4 Hz), 126.8 (d, JC–P = 10.0 Hz), 125.1 (d, JC–P = 9.3 Hz), 116.4
=
Ph
P
=
Pd-L
O
Br
(d, JC–P = 10.0 Hz), 113.7 (d, JC–P = 1.5 Hz), 55.1, 34.4 (d, JC–P
=
69.3 Hz).
O
P
31P{1H} NMR (162 MHz, CDCl3): δ = 22.7 (s).
HRMS (ESI): m/z [M]+ calcd for C20H17O2P: 320.0966; found:
Ph
Ph
Pd
320.0960.
K2CO3
O
P
L
(c)
t-BuCO2H
5,6-Dihydro-8-nitro-5-phenyl-phosphanthridine 5-Oxide (2e)
Yield: 65.1 mg (93%); white solid; mp 183–185 °C.
Br Pd
L
KHCO3
t-BuCO2K
FTIR (neat): 3062, 2960, 2916, 1563, 1436, 1335, 1184, 1115,
1104, 1027, 927, 908, 844, 830, 810, 750, 740, 724, 708, 691 cm−1.
1H NMR (400 MHz, CDCl3): δ = 8.21 (d, J = 8.8 Hz, 1 H), 8.08 (d,
J = 2.0 Hz, 1 H), 7.98–7.91 (m, 3 H), 7.77 (t, J = 7.6 Hz, 1 H), 7.60
(t, J = 7.6 Hz, 1 H), 7.58–7.46 (m, 3 H), 7.39–7.35 (m, 2 H), 3.77
(dd, J = 20.4, 16.0 Hz, 1 H), 3.38 (dd, J = 16.0, 13.6 Hz, 1 H).
(a)
O
P
Ph
Ph
H
13C NMR (100 MHz, CDCl3): δ = 147.1, 140.0 (d, JC–P = 9.6 Hz),
O
Pd
P
O
L
O
137.9 (d, JC–P = 7.1 Hz), 133.5 (d, JC–P = 2.2 Hz), 132.4 (d, JC–P
2.6 Hz), 131.41 (d, JC–P = 6.7 Hz), 131.37 (d, JC–P = 6.3 Hz), 130.8
(d, JC–P = 10.0 Hz), 130.04 (d, JC–P = 103.8 Hz), 130.01 (d, JC–P
11.2 Hz), 128.7 (d, JC–P = 11.9 Hz), 128.6 (d, JC–P = 99.4 Hz), 127.6
(d, JC–P = 2.2 Hz), 126.8 (d, JC–P = 8.9 Hz), 126.1 (d, JC–P
10.0 Hz), 123.4 (d, JC–P = 1.5 Hz), 34.3 (d, JC–P = 69.4 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 20.3 (s).
HRMS (ESI): m/z [M]+ calcd for C19H14NO3P: 335.0711; found:
=
O
KBr
t-Bu
R
Pd
=
O
L
(b)
=
Scheme 4 Proposed catalytic pathway
31P{1H} NMR (162 MHz, CDCl3): δ = 25.3 (s).
335.0686.
5,6-Dihydro-5-phenyl-phosphanthridine 5-Oxide (2c)
Yield: 56.8 mg (98%); white solid; mp 119–121 °C.
5,6-Dihydro-7-chloro-5-phenyl-phosphanthridine 5-Oxide (2f)
Yield: 63.6 mg (98%); white solid; mp 165–167 °C.
FTIR (neat): 3055, 2947, 2885, 1589, 1557, 1473, 1435, 1392,
1312, 1223, 1192, 1154, 1115, 1071, 832, 803, 746, 727, 716, 694
cm−1.
FTIR (neat): 3069, 3055, 2991, 2883, 1589, 1552, 1475, 1439,
1419, 1233, 1196, 1158, 1142, 1119, 1076, 842, 830, 811, 797, 752,
726 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.93 (dd, J = 12.0, 7.2 Hz, 1 H),
7.84 (dd, J = 8.0, 4.8 Hz, 1 H), 7.74 (d, J = 7.6 Hz, 1 H), 7.64 (t, J =
8.0 Hz, 1 H), 7.54–7.49 (m, 2 H), 7.48–7.42 (m, 1 H), 7.40–7.32
(m, 2 H), 7.31–7.25 (m, 2 H), 7.20 (t, J = 7.2 Hz, 1 H), 7.14 (d, J =
7.6 Hz, 1 H), 3.69 (dd, J = 21.2, 16.0 Hz, 1 H), 3.43 (dd, J = 16.0,
14.0 Hz, 1 H).
1H NMR (400 MHz, CDCl3): δ = 7.97 (dd, J = 12.0, 7.6 Hz, 1 H),
7.82 (dd, J = 7.6, 5.2 Hz, 1 H), 7.70–7.64 (m, 2 H), 7.56–7.50 (m,
3 H), 7.43 (t, J = 7.2 Hz, 1 H), 7.36–7.23 (m, 4 H), 3.99 (dd, J =
16.0, 14.8 Hz, 1 H), 3.60 (dd, J = 20.0, 16.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.6 (d, JC–P = 7.8 Hz), 136.2 (d,
J
C–P = 10.7 Hz), 135.3 (d, JC–P = 9.3 Hz), 133.0 (d, JC–P = 2.6 Hz),
132.0 (d, JC–P = 2.6 Hz), 130.81 (d, JC–P = 6.7 Hz), 130.80 (d, JC–P
103.2 Hz), 129.4 (d, JC–P = 1.1 Hz), 128.7 (d, JC–P = 3.4 Hz), 128.6
(d, JC–P = 6.0 Hz), 128.4 (d, JC–P = 12.3 Hz), 127.8 (d, JC–P
13C NMR (100 MHz, CDCl3): δ = 140.0 (d, JC–P = 7.5 Hz), 134.1 (d,
=
JC–P = 10.0 Hz), 132.9 (d, JC–P = 2.6 Hz), 131.7 (d, JC–P = 2.6 Hz),
131.25 (d, JC–P = 10.1 Hz), 131.20 (d, JC–P = 101.8 Hz), 130.8 (d,
JC–P = 7.1 Hz), 130.6 (d, JC–P = 9.6 Hz), 129.2 (d, JC–P = 6.4 Hz),
128.8, 128.3 (d, JC–P = 1.9 Hz), 128.2 (d, JC–P = 11.9 Hz), 128.1 (d,
=
100.6 Hz), 127.7 (d, JC–P = 4.6 Hz), 126.4 (d, JC–P = 9.2 Hz), 125.3
(d, JC–P = 2.2 Hz), 123.4 (d, JC–P = 1.5 Hz), 29.6 (d, JC–P = 70.5 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 22.1 (s).
HRMS (ESI): m/z [M]+ calcd for C19H14ClOP: 324.0471; found:
324.0463.
JC–P = 11.2 Hz), 128.0 (d, JC–P = 99.2 Hz), 126.5 (d, JC–P = 2.2 Hz),
125.7 (d, JC–P = 9.3 Hz), 34.2 (d, JC–P = 69.6 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 21.8 (s).
HRMS (ESI): m/z [M]+ calcd for C19H15OP: 290.0861; found:
290.0863.
5,6-Dihydro-8-chloro-5-phenyl-phosphanthridine 5-Oxide (2g)
Yield: 61.1 mg (94%); white solid; mp 156–158 °C.
5,6-Dihydro-8-methoxy-5-phenyl-phosphanthridine 5-Oxide
(2d)
Yield: 50.1 mg (78%); white solid; mp 159–161 °C.
FTIR (neat): 3099, 3055, 3021, 2866, 1589, 1551, 1472, 1435,
1381, 1192, 1142, 1128, 1110, 885, 834, 825, 787, 765, 755, 739,
732, 713, 690, 651 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.92 (dd, J = 12.0, 7.6 Hz, 1 H),
7.82 (dd, J = 7.6, 4.8 Hz, 1 H), 7.71–7.64 (m, 2 H), 7.57–7.42 (m,
4 H), 7.37–7.31 (m, 3 H), 7.18 (d, J = 1.6 Hz, 1 H), 3.67 (dd, J =
20.8, 16.0 Hz, 1 H), 3.42 (dd, J = 16.0, 13.6 Hz, 1 H).
FTIR (neat): 3077, 3050, 3005, 2962, 2917, 2879, 2831, 1606,
1590, 1504, 1465, 1436, 1315, 1230, 1182, 1145, 1117, 1105, 1077,
1033, 938, 861, 839, 820, 771, 756, 745, 718, 709, 698 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.88 (ddd, J = 12.4, 7.6, 1.2 Hz,
1 H), 7.75 (dd, J = 8.0, 4.8 Hz, 1 H), 7.67 (d, J = 8.8 Hz, 1 H), 7.60
(t, J = 8.0 Hz, 1 H), 7.56–7.50 (m, 2 H), 7.41–7.36 (m, 2 H), 7.31–
7.26 (m, 2 H), 6.87 (dd, J = 8.8, 2.4 Hz, 1 H), 6.68 (d, J = 2.4 Hz,
1 H), 3.75 (s, 3 H), 3.67 (dd, J = 20.8, 16.0 Hz, 1 H), 3.38 (dd, J =
16.0, 14.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.0 (d, JC–P = 7.4 Hz), 134.3,
133.1 (d, JC–P = 2.6 Hz), 132.7 (d, JC–P = 10.0 Hz), 132.0 (d, JC–P
2.6 Hz), 131.1 (d, JC–P = 10.4 Hz), 131.0 (d, JC–P = 1.5 Hz), 130.9
(d, JC–P = 4.8 Hz), 130.69 (d, JC–P = 101.4 Hz), 130.67 (d, JC–P
=
=
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Phosphorus Heterocycle Synthesis
1071
9.6 Hz), 128.5, 128.42 (d, JC–P = 8.5 Hz), 128.41 (d, JC–P = 12.4 Hz),
130.6 (d, JC–P = 9.6 Hz), 130.5 (d, J = 102.1 Hz), 130.0 (d, JC–P
=
127.8 (d, JC–P = 2.2 Hz), 127.7 (d, JC–P = 99.9 Hz), 125.7 (d, JC–P
=
8.9 Hz), 129.9 (d, JC–P = 101.0 Hz), 129.5 (d, JC–P = 7.1 Hz), 128.5
(d, JC–P = 8.9 Hz), 128.1 (d, JC–P = 10.4 Hz), 128.0, 127.5 (d, J =
10.2 Hz), 35.3 (d, JC–P = 69.5 Hz), 22.6.
31P{1H} NMR (162 MHz, CDCl3): δ = 23.2 (s).
9.3 Hz), 34.0 (d, JC–P = 69.4 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 21.8 (s).
HRMS (ESI): m/z [M]+ calcd for C19H14ClOP: 324.0471; found:
324.0464.
HRMS (ESI): m/z [M]+ calcd for C20H17OP: 304.1017; found:
304.1010.
5,6-Dihydro-7-fluoro-5-phenyl-phosphanthridine 5-Oxide (2h)
Yield: 60.4 mg (98%); white solid; mp 137–138 °C.
4-Methyl-5,6-dihydro-5-(2-methylphenyl)phosphanthridine
5-Oxide (2k)
Yield: 50.3 mg (79%); white solid; mp 60–63 °C.
FTIR (neat): 3062, 2953, 2918, 2849, 1611, 1589, 1557, 1452,
1435, 1391, 1240, 1223, 1199, 1185, 1147, 1134, 1117, 1094, 887,
859, 832, 804, 768, 748, 721, 695, 665 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.97 (ddd, J = 12.4, 7.2, 1.2 Hz,
1 H), 7.86 (dd, J = 7.6, 4.8 Hz, 1 H), 7.69 (t, J = 7.6 Hz, 1 H), 7.58–
7.49 (m, 4 H), 7.43 (td, J = 7.6, 4.8 Hz, 1 H), 7.35–7.28 (m, 3 H),
7.02 (t, J = 8.4 Hz, 1 H), 3.72 (dd, J = 16.4, 14.0 Hz, 1 H), 3.47 (dd,
J = 20.4, 16.4 Hz, 1 H).
FTIR (neat): 3052, 3010, 2923, 2893, 2848, 1586, 1557, 1449,
1381, 1281, 1239, 1192, 1158, 1134, 1072, 1030, 874, 834, 803,
753, 678 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.67 (dd, J = 8.0, 4.4 Hz, 1 H),
7.58–7.53 (m, 2 H), 7.30–7.10 (m, 6 H), 7.05 (d, J = 7.6 Hz, 1 H),
6.96 (t, J = 7.2 Hz, 1 H), 3.72 (dd, J = 21.2, 16.0 Hz, 1 H), 3.51 (dd,
J = 15.6, 12.8 Hz, 1 H), 2.66 (s, 3 H), 2.60 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 143.8 (d, JC–P = 6.3 Hz), 141.5 (d,
JC–P = 7.4 Hz), 141.4 (d, J = 8.6 Hz), 135.0 (d, JC–P = 10.4 Hz),
132.7 (d, JC–P = 1.3 Hz), 132.1 (d, JC–P = 12.6 Hz), 131.75, 131.68
(d, JC–P = 7.8 Hz), 131.2 (d, JC–P = 10.0 Hz), 130.1 (d, J = 9.3 Hz),
129.2 (d, JC–P = 97.6 Hz), 129.0 (d, JC–P = 6.6 Hz), 128.4, 128.1 (d,
13C NMR (100 MHz, CDCl3): δ = 160.5 (dd, JC–F = 245.3 Hz, JC–P
=
8.3 Hz), 139.4 (d, J = 7.2, 3.1 Hz), 136.1 (d, J = 10.6, 3.4 Hz), 133.1
(d, JC–P = 2.5 Hz), 132.0 (d, JC–P = 3.0 Hz), 131.1 (d, JC–P = 6.8 Hz),
131.0 (d, JC–P = 103.5 Hz), 130.6 (d, JC–P = 9.9 Hz), 129.0 (d, J =
9.1, 1.9 Hz), 128.7 (d, JC–P = 11.0 Hz), 128.5 (d, JC–P = 12.9 Hz),
127.9 (d, JC–P = 100.0 Hz), 126.2 (d, JC–P = 8.7 Hz), 122.1 (d, J =
3.0, 2.3 Hz), 116.9 (d, J = 17.8, 5.3 Hz), 115.5 (d, J = 23.2, 0.8 Hz),
24.7 (d, J = 61.6, 4.6 Hz).
J
C–P = 1.9 Hz), 127.5 (d, JC–P = 2.6 Hz), 125.9 (d, JC–P = 99.5 Hz),
125.3 (d, J = 12.6 Hz), 124.3 (d, JC–P = 9.0 Hz), 34.7 (d, JC–P
=
69.7 Hz), 22.1 (d, JC–P = 4.9 Hz), 21.1 (d, JC–P = 3.7 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 25.7 (s).
HRMS (ESI): m/z [M + H]+ calcd for C21H20OP: 319.1246; found:
319.1249.
31P{1H} NMR (162 MHz, CDCl3): δ = 22.0 (s).
HRMS (ESI): m/z [M]+ calcd for C19H14FOP: 308.0766; found:
308.0760.
5,6-Dihydro-8-trifluoromethyl-5-phenyl-phosphanthridine
5-Oxide (2i)
Yield: 60.9 mg (85%); white solid; mp 269–271 °C.
2-Methoxy-5,6-dihydro-5-(4-methoxyphenyl)-phosphanthri-
dine 5-Oxide (2l)
Yield: 66.5 mg (95%); white solid; mp 62–64 °C.
FTIR (neat): 3068, 2869, 1615, 1591, 1437, 1412, 1385, 1334,
1315, 1270, 1217, 1192, 1168, 1140, 1118, 1105, 1081, 1019, 930,
851, 837, 794, 781, 766, 743, 713, 695, 654 cm−1.
FTIR (neat): 3052, 3010, 2923, 2893, 2848, 1586, 1557, 1449,
1239, 1192, 1158, 1134, 834, 803, 753, 678, 642 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.82 (dd, J = 12.0, 8.4 Hz, 1 H),
7.73 (d, J = 7.6 Hz, 1 H), 7.43 (dd, J = 7.6, 4.8 Hz, 2 H), 7.36–7.30
(m, 2 H), 7.22 (t, J = 7.6 Hz, 1 H), 7.15 (d, J = 7.6 Hz, 1 H), 6.98
(dd, J = 8.4, 0.8 Hz, 1 H), 6.80 (dd, J = 8.8, 2.0 Hz, 2 H), 3.91 (s,
3 H), 3.74 (s, 3 H), 3.64 (dd, J = 20.4, 16.0 Hz, 1 H), 3.38 (dd, J =
16.0, 14.0 Hz, 1 H).
1H NMR (400 MHz, CDCl3): δ = 8.01 (s, 1 H), 7.92–7.88 (m, 2 H),
7.73 (t, J = 8.0 Hz, 1 H), 7.58–7.42 (m, 5 H), 7.38–7.30 (m, 3 H),
3.73 (dd, J = 20.8, 16.0 Hz, 1 H), 3.47 (dd, J = 16.0, 13.6 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 138.8 (d, JC–P = 27.4 Hz), 135.9
(d, JC–P = 10.0 Hz), 133.5 (dd, J = 6.7, 1.5 Hz), 133.4 (d, JC–P
=
2.2 Hz), 132.2 (d, JC–P = 2.6 Hz), 131.8 (d, JC–P = 9.7 Hz), 131.2 (d,
JC–P = 7.1 Hz), 130.82 (d, JC–P = 10.0 Hz), 130.80 (dd, J = 32.6,
1.9 Hz), 130.6 (d, JC–P = 103.3 Hz), 129.1 (d, JC–P = 11.2 Hz), 128.6
13C NMR (100 MHz, CDCl3): δ = 163.0 (d, JC–P = 2.7 Hz), 162.0 (d,
J
C–P = 2.7 Hz), 141.7 (d, J = 8.3 Hz), 133.8 (d, JC–P = 9.9 Hz), 132.5
(d, JC–P = 7.6 Hz), 132.3 (d, JC–P = 10.0 Hz), 131.1 (d, JC–P
9.8 Hz), 129.7 (d, JC–P = 6.5 Hz), 128.6, 128.0 (d, J = 1.5 Hz), 126.2
(d, JC–P = 1.9 Hz), 122.2 (d, JC–P = 108.7 Hz), 119.5 (d, JC–P
=
(d, JC–P = 12.3 Hz), 128.1 (d, JC–P = 99.5 Hz), 126.1 (d, JC–P
=
9.3 Hz), 125.3 (q, J = 3.7 Hz), 123.8 (q, JC–F = 273.1 Hz), 123.5 (m),
34.4 (d, JC–P = 69.0 Hz).
=
106.1 Hz), 113.6 (d, JC–P = 12.9 Hz), 112.9 (d, JC–P = 11.8 Hz),
111.7 (d, J = 9.9 Hz), 55.1, 54.8, 34.3 (d, JC–P = 70.8 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 19.6 (s).
HRMS (ESI): m/z [M + H]+ calcd for C21H20O3P: 351.1145; found:
351.1149.
31P{1H} NMR (162 MHz, CDCl3): δ = 20.9 (s).
HRMS (ESI): m/z [M]+ calcd for C20H14F3OP: 358.0734; found:
358.0726.
5,6-Dihydro-10-methyl-5-phenyl-phosphanthridine 5-Oxide
(2j)
Yield: 50.5 mg (83%); white solid; mp 158–159 °C.
2-Chloro-5,6-dihydro-5-(4-chlorophenyl)phosphanthridine
5-Oxide (2m)
Yield: 57.4 mg (80%); white solid; mp 80–82 °C.
FTIR (neat): 3055, 2986, 2943, 2873, 1587, 1574, 1557, 1471,
1447, 1434, 1208, 1171, 1156, 1141, 1116, 845, 809, 784, 770, 753,
746, 727, 694 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.99 (dd, J = 12.8, 8.0 Hz, 1 H),
7.66–7.62 (m, 2 H), 7.50–7.44 (m, 3 H), 7.39 (d, J = 6.8 Hz, 1 H),
7.29–7.25 (m, 2 H), 7.20 (d, J = 7.6 Hz, 1 H), 7.08 (t, J = 7.6 Hz,
1 H), 6.98 (d, J = 7.6 Hz, 1 H), 3.58 (dd, J = 20.0, 15.6 Hz, 1 H),
3.34 (t, J = 15.2 Hz, 1 H), 2.54 (s, 3 H).
FTIR (neat): 3055, 2944, 2873, 1643, 1580, 1546, 1480, 1437,
1384, 1222, 1195, 1159, 1119, 1085, 1013, 884, 810, 786, 766, 745,
720, 694, 632, 624, 607 cm−1.
1H NMR (400 MHz, CDCl3): δ = 7.90–7.84 (m, 2 H), 7.73 (d, J =
8.0 Hz, 1 H), 7.48–7.38 (m, 4 H), 7.30–7.25 (m, 3 H), 7.18 (d, J =
8.0 Hz, 1 H), 3.73 (dd, J = 21.2, 16.4 Hz, 1 H), 3.59 (dd, J = 16.0,
14.0 Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 139.5 (d, JC–P = 7.5 Hz), 135.4 (d,
13C NMR (100 MHz, CDCl3): δ = 142.0 (d, JC–P = 8.0 Hz), 139.9 (d,
J = 3.4 Hz), 138.7 (d, JC–P = 3.5 Hz), 133.1 (d, JC–P = 9.5 Hz), 132.5
JC–P = 2.6 Hz), 134.2 (d, J = 9.6 Hz), 131.8 (d, JC–P = 2.2 Hz), 131.6
(d, JC–P = 2.6 Hz), 131.4 (d, JC–P = 2.3 Hz), 130.8 (d, JC–P = 7.0 Hz),
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 1067–1072

1072
Y.-R. Chen, W.-L. Duan
PAPER
(d, JC–P = 7.2 Hz), 132.1 (d, JC–P = 10.3 Hz), 131.6 (d, JC–P
10.3 Hz), 129.8, 129.45 (d, J = 102.6 Hz), 129.40 (d, JC–P = 6.5 Hz),
128.87 (d, JC–P = 12.5 Hz), 128.86 (d, JC–P = 1.9 Hz), 128.5 (d, JC–P
1.8 Hz), 126.8 (d, JC–P = 2.7 Hz), 126.4 (d, J = 9.5 Hz), 126.1 (d,
JC–P = 101.1 Hz), 34.2 (d, JC–P = 70.2 Hz).
31P{1H} NMR (162 MHz, CDCl3): δ = 21.1 (s).
HRMS (ESI): m/z [M + H]+ calcd for C19H14Cl2OP: 359.0154;
=
Ye, M.; Xiao, K.-J.; Li, S.; Yu, J.-Q. J. Am. Chem. Soc. 2013,
135, 9322. (d) Meng, X.; Kim, S. Org. Lett. 2013, 15, 1910.
(e) Chan, L. Y.; Kim, S.; Ryu, T.; Lee, P. H. Chem.
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(m) Itoh, M.; Hashimoto, Y.; Hirano, K.; Satoh, T.; Miura,
M. J. Org. Chem. 2013, 78, 8098. (n) Li, C.; Yano, T.;
Ishida, N.; Murakami, M. Angew. Chem. Int. Ed. 2013, 52,
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Int. Ed. 2013, 52, 11892. (p) Wang, H.-Li.; Hu, R.-B.;
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=
found: 359.0154.
Acknowledgment
We are grateful for financial support from the National Basic Re-
search Program (2010CB833300), the National Science Foundation
of China (20902099, 21172238), and the Chinese Academy of Sci-
ences.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
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Synthesis 2014, 46, 1067–1072
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