Palladium-Catalyzed Hydroarylation of Diazocarboxylates and Diazophosphonates

Article abstract of DOI:10.1055/s-0039-1690758

A simple synthetic procedure for the Pd-catalyzed hydro-arylation of diazoacetic ester has been previously developed in our laboratory. Now we have applied this methodology for hydroarylation of α-diazocarboxylates/α-diazophosphonates. Diazo compounds reacted with aryl iodides and formic acid to afford diarylated esters or phosphonates in yields up to 71percent.

Full text of DOI:10.1055/s-0039-1690758

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–F
paper
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S. M. Golitsin et al.
Paper
Synthesis
Palladium-Catalyzed Hydroarylation of Diazocarboxylates and
Diazophosphonates
Sergey M. Golitsin
Irina P. Beletskaya
Igor D. Titanyuk*
N2
Ar
EWG
PdCl2(PPh3)2 (5 mol%)
Et3N
Ar
H
0
0
0
0-
0
0
0
2-7
5
1
9-5
6
0
2
HCO2H
+
EWG
R
17 examples
Department of Chemistry, Moscow State University, 119991,
Leninskie gory 1-3, Moscow, Russian Federation
titanyuk@org.chem.msu.ru
I
up to 71% yield
R
EWG = CO2Et; P(O)(OEt)2
Received: 13.09.2019
Accepted after revision: 10.11.2019
Published online: 27.11.2019
In the latter case, a organopalladium intermediate that
is generated can be captured with a nucleophile.4–6 The hy-
dride ion generated from formic acid is a suitable nucleo-
phile for this type reaction. Our research group has elaborat-
ed Pd-catalyzed three-component hydroarylation coupling:
aryl iodides reacted with -diazocarboxylates/-diazophos-
phonates and formic acid to generate mono- or diarylace-
tates and diarylphosphonates.
DOI: 10.1055/s-0039-1690758; Art ID: ss-2019-z0526-op
Abstract A simple synthetic procedure for the Pd-catalyzed hydro-
arylation of diazoacetic ester has been previously developed in our labo-
ratory. Now we have applied this methodology for hydroarylation of
-diazocarboxylates/-diazophosphonates. Diazo compounds reacted
with aryl iodides and formic acid to afford diarylated esters or phospho-
nates in yields up to 71%.
Recently, J. Wang and co-workers have reported Pd-cat-
alyzed reductive coupling of ethyl diazoacetate (EDA) with
aryl iodides leading to the formation of ,-diarylacetates.
Although their methodology provides high yield and wide
scope of products, it requires a stoichiometric amount of
silver carbonate.7
The coupling of aryl iodides with EDA in the presence of
formic acid and Et3N was investigated previously by our re-
search team (Scheme 2).8
Key words hydroarylation, diazo compounds, arylacetates, palladium
catalysis, cross coupling, phosphonates
The transition-metal-catalyzed transformation of -di-
azocarbonyl compounds has become a standard method in
organic synthesis. The approach has traditionally been used
for carbene generation in reactions such as X–H insertion
(X = C, N, O, S), cyclopropanation, and cycloaddition to ni-
triles and carbonyl compounds.1 More recently, the scope of
their application was widened significantly to include Pd-
catalyzed cross-coupling reactions, mostly due to the im-
portant contributions made by J. Wang and co-workers.2
Depending on the reaction conditions, two types of cross-
coupling reactions can be carried out: (i) with retention of
diazo group leading to formation of aryl-substituted diazo
compound;3 (ii) with the loss of diazo function (Scheme 1).4
I
PdCl2(PPh3)2, Et3N
CO2Et
EDA
R
+
R
HCO2H, MeCN
1
2, 50–85%
Scheme 2 Hydroarylation of EDA with aryl iodides8
A number of aryl iodides were subjected to three-com-
ponent hydroarylation under the optimized reaction condi-
tions. Exploration of substrates containing electron-with-
drawing groups (EWG) as well as iodobenzene allowed a
range of ethyl arylacetates 2 to be synthesized in respect-
able yields (50–85%).
In this context, we have been interested in continuing
our previous studies in an attempt to extend our method to
a wider range of substrates. Herein we report a solution to
this issue.
N2
N2
N2
Ar-
Ar
EWG
Pd
EWG
H
EWG
+
X
Ar
H
Ar-Pd-X
Pd
Pd
X
Ar
H
EWG
EWG
EWG = CO2R; P(O)(OR)2
Scheme 1
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–F
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
S. M. Golitsin et al.
Paper
Synthesis
The coupling of methyl 4-iodobenzoate (1a) with
phenyldiazoacetate (3a) in the presence of formic acid and
Et3N was investigated as a model reaction for the prepara-
tion of diarylated products (Table 1).
PdCl2(PPh3)2 as the catalyst, triethylamine as the base, 1,2-
DCE as the solvent, and reflux temperature (Table 1, entry
10).
The coupling of aryl iodides 1 with -aryldiazoacetates
3 in the presence of formic acid and triethylamine provided
diarylacetates 4a–l in a yield up to 71% (Table 2). The scope
of the proposed method was examined by application of
ethyl -aryldiazocarboxylates (3a–d) in the hydroarylation
reaction with a series of aryl iodides 1 under the optimized
reaction conditions.
Table 1 Optimization of the Reaction Conditions in the Model Reactiona
Ph
I
N2
HCO2H
+
CO2Et
[Pd], base
Ph
CO2Et
MeO2C
MeO2C
1a
3a
4a
Table 2 Hydroarylation of -Aryldiazoacetates 3 with Aryl Iodides 1a
Entry
Catalyst
PdCl2(PPh3)2
Base
Et3N
Solvent
Yield (%)b
N2
Ar
1
2
MeCN
MeCN
MeCN
MeCN
1,2-DCE
38
29
CO2Et
CO2Et
PdCl2(PPh3)2, Et3N
HCO2H, DCE
Pd2dba3+PPh3
PdCl2(PCy3)2
Pd(PPh3)4
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
DBU
Py
R
R
ArI
+
3
0
3a–d
1a–h
4a–l
4
42
Entry
R
Ar
Product
Yield (%)b
5
Pd(PPh3)4
60
6
Pd(PPh3)4
benzene
EtOH
42
1
2
H (3a)
H (3a)
H (3a)
H (3a)
H (3a)
H (3a)
H (3a)
H (3a)
p-MeO2CC6H4 (1a)
4a
4b
4c
4d
4e
4f
70
45
53
66
71
55
69
trace
37
35
43
64
7
Pd(PPh3)4
traces
52
m-MeO2CC6H4 (1b)
3-C5H4N (1c)
8
Pd(PPh3)4
THF
3
9
Pd(PPh3)4
CHCl3
20
4
p-NCC6H4 (1d)
p-O2NC6H4 (1e)
p-F3CC6H4 (1f)
10
11
12
13
14
15c
16d
17e
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
1,2-DCE
70
traces
20
5
6
7
p-AcC6H4 (1g)
4g
4h
4i
DIPEA
K2CO3
Et3N
24
8
m-MeC6H4 (1h)
p-O2NC6H4 (1e)
m-MeO2CC6H4 (1b)
p-MeO2CC6H4 (1a)
p-NCC6H4 (1d)
30
9
p-CN (3b)
0
10
11
12
p-CN (3b)
4j
Et3N
31
p-MeO2C(3c)
m-Me (3d)
4k
4l
Et3N
55
a Reaction conditions: 1a (0.5 mmol), 2a (0.75 mmol), base (2.5 mmol),
HCO2H (0.5 mmol), Pd catalyst (0.05 mmol), reflux.
b Isolated yield.
a Reaction conditions: 1 (0.5 mmol), 2 (0.75 mmol), Et3N (1.25 mmol),
HCO2H (0.5 mmol), Pd(PPh3)2Cl2 (0.025 mmol), DCE, reflux for 2 h.
b Isolated yield.
c Carried out at 20 °C.
d Carried out at 40 °C.
Exploration of EWG-containing aryl iodides and 3-io-
dopyridine allowed phenylarylacetates 4a–g to be synthe-
sized in good yields (40–71%). Aryl iodide containing elec-
tron-donating groups (m-tolyl iodide) exhibited poor reac-
tivity and provided product 4h in trace amounts (Table 2,
entry 8). A significant influence of the electronic effects of
substituents on the aromatic ring of the diazo compound
was observed. It was opposite to that of aryl iodides: the
presence of electron-withdrawing group on the benzene
ring of diazo compound 3 decreased the yield of product
compared with that of unsubstituted phenyldiazoacetate 3a
(entries 9–11). In contrast, diazocarboxylate 3d, containing
an electron-donating m-CH3 group, provided good yield of
product 4l (entry 12).
e Carried out at 60 °C.
Screening of catalytic systems revealed that application
of palladium catalysts Pd(PPh3)4 and PdCl2(PPh3)2 was more
effective than Pd2(dba)3 (Table 1, entries 1–3). The investi-
gated chemical reaction appeared to be sensitive not only
to the selected catalyst but also to the choice of solvent and
base. The reaction afforded hydroarylated product 4a with
higher yield (entries 5, 10) using 1,2-DCE as solvent. Tri-
ethylamine appeared to be the best base for this reaction;
other bases such as K2CO3, pyridine, DIPEA or DBU were
found to be ineffective or less effective in this reaction.
Reaction temperature variation was further investigat-
ed. Attempts to obtain hydroarylated product 4a at room
temperature failed. Increase of reaction temperature greatly
influenced the amount of synthesized product. In summa-
ry, it was found that the most favorable conditions were:
The phosphonate (PO32–) moiety is a common structural
fragment that is present in a wide range of biologically
active compounds.9,10 Despite structural and electronic dif-
ferences between phosphonate and carboxylic functional-
ities (in terms of size, shape, acidity, and geometry) the
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–F

C
S. M. Golitsin et al.
Paper
Synthesis
phosphonate functionality is regarded as a bioisostere of
the carboxylic group. -Diazophosphonates have received
much more attention in organic synthesis in recent years;
they are widely used for the preparation of derivatives of
phosphonic acids.11
We also applied the above procedure for the synthesis of
diarylmethylphosphonates 6a–e (Table 3). Diazophospho-
nates 5 exhibited comparable reactivity under analogous
reaction conditions yielding the corresponding ,-diaryl-
phosphonates 6a–e in good yield.
N2
PPh3
Ar Pd
PPh3
R
EWG
Ar Pd
R
I
I
EWG
– N2
– PPh3
PPh3
Ar-I
B
A
HCO2H
PdCl2(PPh3)2
[Pd(PPh3)2]
Ph3P
I
Pd
ArRCH-EWG
EWG
PPh3
Pd
Ar
R
Table 3 Hydroarylation of Diazophosphonates 5 with Aryl Iodides 1a
C
Ph3P
H
O
H
N2
–
HCO2
Ph3P
P(O)(OEt)2
EWG
O
Ar
R1
R1
Pd
R
5a,b
PdCl2(PPh3)2, Et3N
EWG
Ar
E
+
– CO2
HCO2H, DCE
P(O)(OEt)2
R
I
R
D
R
6
EWG = CO2Et, P(O)(OEt)2
1
Scheme 3 Mechanism of hydroarylation
Entry
R1
R
Product
Yield (%)b
1
2
3
4
5
p-MeO (5a)
H (5b)
p-MeO2C
p-O2N
6a
6b
6c
6d
6e
66
60
54
63
71
All solvents were distilled prior to use. Acetonitrile and 1,2-dichlo-
roethane were dried by distillation over P2O5. Chromatography was
carried out using 230–400 mesh silica gel (Merck 40/60). 1H NMR
spectra were recorded with a commercial Agilent 400-MR (400 MHz)
instrument. Chemical shifts are reported in ppm from tetramethylsi-
lane with the solvent resonance as the internal standard (CDCl3,  =
7.26 ppm). 13C{1H} NMR spectra were collected with commercial Agi-
lent 400-MR (100 MHz) instrument with complete proton decou-
pling. 31P and 19F NMR spectra were recorded with a commercial Agi-
lent 400-MR (162 MHz and 376 MHz respectively) instrument. HRMS
(ESI) were recorded with a commercial apparatus. Published proce-
dures were applied for the synthesis of aryldiazocarboxylates (3)3a
and aryldiazophosphonates (5).3b
H (5b)
p-MeO2C
p-NC
H (5b)
H (5b)
p-Ac
a Reaction conditions: 1 (0.5 mmol), 5 (0.5 mmol), Et3N (1.25 mmol),
HCO2H (0.5 mmol), Pd(PPh3)2Cl2 (0.025 mmol), DCE, reflux for 4 h.
b Isolated yield.
The proposed mechanism of hydroarylation is present-
ed in Scheme 3. Palladium dichloride complex can be easily
reduced by formic acid resulting in Pd(0) species. The cata-
lytic cycle starts with oxidative addition to form arylpalla-
dium iodide complex A. Then addition of diazo compound
to this complex could generate carbene complex B.12 Migra-
tion of the aryl group to the carbene center, which is now
described in several publications,13,14 would produce ben-
zylic intermediate C. The exchange complex D can be easily
produced by substitution of halogen with formate anion
followed by liberation of carbon dioxide (complex E). Re-
ductive elimination should provide the product simultane-
ously with regeneration of the Pd(0) species.
Pd-Catalyzed Cross-Coupling between Aryl Iodides and Aryldiazo-
acetates; Typical Procedure A
To a mixture of aryl iodide (1a–h; 0.5 mmol), aryldiazoacetate (3a–d;
0.75 mmol), and PdCl2(PPh3)2 (18 mg, 0.025 mmol) in a Schlenk flask
under argon atmosphere, Et3N (127 mg, 1.25 mmol) and formic acid
(23 mg, 0.5 mmol) in DCE (3 mL) were added. The mixture was stirred
and heated at 80 °C until 1a–h disappeared (2–4 h, monitoring by
TLC). Solvent was evaporated under reduced pressure. Pure product 4
was isolated by column chromatography (EtOAc/petrol ether, 1:5 v/v).
In conclusion, this report describes a simple method for
palladium-catalyzed hydroarylation of diazocarboxylates
and diazophosphonates in the presence of formic acid. The
proposed reaction can serve as a pathway for the prepara-
tion of diarylated carboxylic acid and phosphonic acid de-
rivatives that are otherwise difficult to access. A range of
arylated products were synthesized in 35–71% yield by ap-
plying this methodology.
Pd-Catalyzed Cross-Coupling between Aryl Iodides and Aryldiazo-
phosphonates; Typical Procedure B
To a mixture of aryl iodide 1 (0.5 mmol), aryldiazophosphonate (5a–
b; 0.5 mmol), and PdCl2(PPh3)2 (18 mg, 0.025 mmol) in a Schlenk flask
under argon atmosphere, Et3N (127 mg, 1.25 mmol) and formic acid
(23 mg, 0.5 mmol) in DCE (3 mL) were added. The mixture was stirred
and heated at 80 °C for 3 h. Solvent was evaporated under reduced
pressure. Pure product 6 was isolated by column chromatography
(EtOAc/petrol ether, 1:1 v/v).
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–F

D
S. M. Golitsin et al.
Paper
Synthesis
Characterization of Synthesized Products
IR (film): 2230, 1738, 1612 cm–1
.
Anal. Calcd for C17H15O2N: C, 76.68; H, 5.66; N, 5.28. Found: C, 76.91;
H, 5.54; N, 5.13.
Ethyl [4-(Methoxycarbonyl)phenyl](phenyl)acetate (4a)
Prepared according to general procedure A from methyl 4-iodobenzo-
ate and phenyldiazoacetate. Reaction time 2 h.
NMR spectral data for this compound were consistent with those in
the literature.7
Yield: 104 mg (70%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.99 (d, J = 8.4 Hz, 2 H), 7.39 (d, J =
8.3 Hz, 2 H), 7.26–7.38 (m, 5 H), 5.05 (s, 1 H), 4.26 (q, J = 7.1 Hz, 2 H),
3.94 (s, 3 H), 1.30 (t, J = 7.1 Hz, 3 H).
Ethyl (4-Nitrophenyl)(phenyl)acetate (4e)
Prepared according to general procedure A from 4-iodo-1-nitroben-
zene and phenyldiazoacetate. Reaction time 1.5 h.
13C{1H} NMR (100 MHz, CDCl3):  = 171.9, 166.8, 143.8, 138.0, 129.8,
Yield: 100 mg (71%); yellow oil.
129.2, 128.7, 128.5, 127.5, 127.2, 61.4, 57.1, 52.1, 14.1.
1H NMR (400 MHz, CDCl3):  = 8.17 (d, J = 8.8 Hz, 2 H), 7.49 (d, J =
8.8 Hz, 2 H), 7.39–7.28 (m, 5 H), 5.10 (s, 1 H), 4.24 (q, J = 7.1 Hz, 2 H),
1.27 (t, J = 7.1 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 171.4, 146.0, 137.4, 129.6, 129.0,
128.9, 128.5, 127.8, 123.7, 61.7, 56.8, 14.1.
IR (film): 1733, 1615, 1290 cm–1
.
Anal. Calcd for C18H18O4: C, 72.48; H, 6.04. Found: C, 72.67; H, 5.91.
NMR spectral data for this compound were consistent with those in
the literature.7
IR (film): 1735, 1520, 1355 cm–1
.
Ethyl [3-(Methoxycarbonyl)phenyl](phenyl)acetate (4b)
Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C, 67.49;
H, 5.31; N, 4.86.
Prepared according to general procedure A from methyl 3-iodobenzo-
ate and phenyldiazoacetate. Reaction time 2.5 h.
NMR spectral data for this compound were consistent with those in
the literature.7
Yield: 67 mg (45%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.02 (bs, 1 H), 7.95 (dt, 1J = 7.7 Hz, 2J =
1.3 Hz, 1 H), 7.53 (dt, 1J = 7.7 Hz, 2J = 1.9 Hz, 1 H), 7.43–7.25 (m, 6 H),
5.06 (s, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 3.90 (s, 3 H), 1.26 (t, J = 7.1 Hz,
3 H).
Ethyl [4-(Trifluoromethyl)phenyl](phenyl)acetate (4f)
Prepared according to general procedure A from 4-trifluoromethyl-1-
iodobenzene and phenyldiazoacetate. Reaction time 3 h.
13C{1H} NMR (100 MHz, CDCl3):  = 172.1, 166.8, 139.2, 138.3, 133.1,
Yield: 85 mg (55%); colorless oil.
130.5, 129.8, 128.9, 128.7, 128.6, 128.3, 127.5, 61.4, 56.9, 52.1, 14.1.
1H NMR (400 MHz, CDCl3):  = 7.57 (d, J = 8.2 Hz, 2 H), 7.44 (d, J =
8.6 Hz, 2 H), 7.38–7.28 (m, 5 H), 5.05 (s, 1 H), 4.23 (d, J = 7.0 Hz, 2 H),
1.25 (t, J = 7.0 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 171.8, 142.7, 137.9, 129.0, 128.8,
128.7 (q, JC–F = 33.4 Hz), 128.5, 127.6, 125.5 (q, JC–F = 3.8 Hz), 123.9 (q,
JC–F = 244 Hz, CF3), 61.5, 56.8, 14.1.
IR (film): 1740, 1610, 1281 cm–1
.
HRMS (ESI): m/z [M + H]+ calcd for C18H18O4: 299.1283; found:
299.1278.
Ethyl (Pyridin-3-yl)(phenyl)acetate (4c)
19F NMR (376 MHz, CDCl3):  = 62.6.
Prepared according to general procedure A from 3-iodopyridine and
phenyldiazoacetate. Reaction time 2.5 h.
Anal. Calcd for C17H15F3O2: C, 66.23; H, 4.90. Found: C, 66.31; H, 5.01.
Yield: 64 mg (53%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.57 (d, J = 2.0 Hz, 1 H), 8.50 (dd, 1J =
4.7 Hz, 2J = 1.5 Hz, 1 H), 7.68 (dt, 1J = 1.7 Hz, 2J = 8.0 Hz, 1 H), 7.21–
7.36 (m, 6 H), 5.01 (s, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 1.25 (t, J = 7.1 Hz,
3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 171.7, 149.9, 148.7, 137.8, 136.1,
134.6, 128.9, 128.4, 127.6, 123.4, 61.6, 54.6, 14.1.
Ethyl (4-Acetylphenyl)(phenyl)acetate (4g)
Prepared according to general procedure A from 4-iodoacetophenone
and phenyldiazoacetate. Reaction time 2 h.
Yield: 98 mg (69%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.92 (d, J = 8.4 Hz, 2 H), 7.44 (d, J =
8.5 Hz, 2 H), 7.36–7.26 (m, 5 H), 5.08 (s, 1 H), 4.23 (d, J = 7.1 Hz, 2 H),
2.58 (s, 3 H), 1.27 (t, J = 7.1 Hz, 3 H).
IR (film): 1730, 1600 cm–1
.
Anal. Calcd for C15H15O2N: C, 74.69; H, 6.22; N, 5.81. Found: C, 74.33;
H, 6.24; N, 5.51.
13C{1H} NMR (100 MHz, CDCl3):  = 197.6, 171.7, 143.9, 137.9, 135.9,
128.9, 128.7, 128.5, 128.4, 127.4, 61.4, 56.9, 26.5, 14.0.
NMR spectral data for this compound were consistent with those in
the literature.15
Anal. Calcd for C18H18O3: C, 76.57; H, 6.43. Found: C, 76.67; H, 6.51.
NMR spectral data for this compound were consistent with those in
the literature.16
Ethyl (4-Cyanophenyl)(phenyl)acetate (4d)
Prepared according to general procedure A from 4-iodobenzonitrile
Ethyl (4-Nitrophenyl)(4-cyanophenyl)acetate (4i)
and phenyldiazoacetate. Reaction time 2 h.
Prepared according to general procedure A from 4-iodo-1-nitroben-
Yield: 87 mg (66%); yellow oil.
zene and (4-cyanophenyl)diazoacetate. Reaction time 3 h.
1H NMR (400 MHz, CDCl3):  = 7.60 (d, J = 8.2 Hz, 2 H), 7.44 (d, J =
8.2 Hz, 2 H), 7.38–7.26 (m, 5 H), 5.06 (s, 1 H), 4.23 (d, J = 7.1 Hz, 2 H),
1.26 (t, J = 7.1 Hz, 3 H).
Yield: 57 mg (37%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 8.19 (d, J = 8.2 Hz, 2 H), 7.64 (d, J =
8.1 Hz, 2 H), 7.48 (d, J = 8.2 Hz, 2 H), 7.42 (d, J = 8.1 Hz, 2 H), 5.14 (s,
1 H), 4.24 (q, J = 7.1 Hz, 2 H), 1.26 (t, J = 7.1 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 171.5, 144.1, 137.5, 132.3, 129.5,
128.9, 128.5, 127.8, 118.7, 111.2, 61.6, 57.0, 14.1.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–F

E
S. M. Golitsin et al.
Paper
Synthesis
13C{1H} NMR (100 MHz, CDCl3):  = 170.4, 147.4, 144.5, 142.5, 132.7,
129.6, 129.4, 124.1, 118.3, 111.9, 62.2, 56.5, 14.0.
1H NMR (400 MHz, CDCl3):  = 7.96 (d, J = 8.2 Hz, 2 H), 7.57 (d, J =
8.2 Hz, 2 H), 7.41 (d, J = 8.5 Hz, 2 H), 6.84 (d, J = 8.5 Hz, 2 H), 4.43 (d,
J = 25.0 Hz, 1 H), 4.00–3.92 (m, 2 H), 3.87 (s, 3 H), 3.87–3.79 (m, 2 H),
3.76 (s, 3 H), 1.11 (t, J = 7.1 Hz, 6 H).
13C{1H} NMR (100 MHz, CDCl3):  = 166.8, 158.8, 142.5, 130.5, 129.8,
129.4, 128.8, 128.0, 114.1, 62.9 (d, J = 6.5 Hz), 62.6 (d, J = 6.5 Hz), 55.2,
52.1, 51.3 (d, J = 138.2 Hz), 16.2.
IR (film): 2235, 1739, 1542, 1347 cm–1
.
Anal. Calcd for C17H14N2O4: C, 65.81; H, 4.52; N, 9.03. Found: C, 65.93;
H, 4.73; N, 8.93.
Ethyl [3-(Methoxycarbonyl)phenyl](4-cyanophenyl)acetate (4j)
31P NMR (162 MHz, CDCl3):  = 24.5.
Prepared according to general procedure A from methyl 3-iodobenzo-
Anal. Calcd for C20H25O6P: C, 61.22; H, 6.42. Found: C, 61.18; H, 6.49.
ate and (4-cyanophenyl)diazoacetate. Reaction time 4 h.
Yield: 56 mg (35%); colorless oil.
Diethyl (4-Nitrophenyl)(phenyl)methylphosphonate (6b)
1H NMR (400 MHz, CDCl3):  = 7.98 (m, 2 H), 7.62 (d, J = 8.3 Hz, 2 H),
7.52–7.48 (m, 1 H), 7.46–7.40 (m, 3 H), 5.09 (s, 1 H), 4.24 (q, J = 7.1 Hz,
2 H), 3.91 (s, 3 H), 1.26 (t, J = 7.1 Hz, 3 H).
Prepared according to general procedure B from 4-iodo-1-nitroben-
zene and diethyl 1-diazo-phenylmethylphosphonate.
Yield: 104 mg (60%); yellow oil.
13C{1H} NMR (100 MHz, CDCl3):  = 172.0, 165.7, 143.5, 136.1, 132.9,
132.4, 131.6, 130.8, 129.7, 129.4, 129.0, 118.5, 108.9, 65.4, 57.2, 51.4,
14.0.
1H NMR (400 MHz, CDCl3):  = 8.15 (d, J = 8.7 Hz, 2 H), 7.70 (d, J =
8.7 Hz, 2 H), 7.49 (d, J = 8.0 Hz, 2 H), 7.35–7.30 (m, 2 H), 7.28–7.24 (m,
1 H), 4.52 (d, J = 25.1 Hz, 1 H), 4.06–3.75 (m, 4 H), 1.14 (t, J = 7.1 Hz,
3 H), 1.09 (t, J = 7.0 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 147.0, 144.6, 135.4, 130.3, 129.4,
128.9, 127.8, 123.7, 63.2 (d, J = 6.7 Hz), 62.7 (d, J = 6.7 Hz), 51.0 (d, J =
139.1 Hz), 16.2.
IR (film): 2232, 1736, 1614 cm–1
.
Anal. Calcd for C19H17NO4: C, 70.58; H, 5.30; N, 4.33. Found: C, 70.41;
H, 5.34; N, 4.24.
Ethyl Bis[4-(methoxycarbonyl)phenyl]acetate (4k)
31P NMR (162 MHz, CDCl3):  = 23.4.
Prepared according to general procedure A from methyl 4-iodobenzo-
Anal. Calcd for C17H20NO5P: C, 58.45; H, 5.77; N, 4.01. Found: C, 58.28;
H, 5.69; N, 4.09.
ate and (4-(methoxycarbonyl)phenyl)diazoacetate. Reaction time 2 h.
Yield: 76 mg (43%); colorless oil.
NMR spectral data for this compound were consistent with those in
the literature.17
1H NMR (400 MHz, CDCl3):  = 7.99 (d, J = 8.0 Hz, 4 H), 7.37 (d, J =
8.0 Hz, 4 H), 5.09 (s, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 3.89 (s, 6 H), 1.24 (t,
J = 7.1 Hz, 3 H).
13C{1H} NMR (100 MHz, CDCl3):  = 171.2, 166.6, 142.9, 129.9, 129.4,
128.6, 61.6, 56.9, 52.1, 14.1.
Diethyl[4-(Methoxycarbonyl)phenyl](phenyl)methylphosphonate
(6c)
Prepared according to general procedure B from methyl 4-iodobenzo-
ate and diethyl 1-diazo-phenylmethylphosphonate.
IR (film): 1725, 1610, 1280 cm–1
.
Anal. Calcd for C20H20O6: C, 67.41; H, 5.66. Found: C, 67.44; H, 5.69.
Yield: 97 mg (54%); colorless oil.
NMR spectral data for this compound were consistent with those in
the literature.7
1H NMR (400 MHz, CDCl3):  = 7.97 (d, J = 8.1 Hz, 2 H), 7.60 (d, J =
7.7 Hz, 2 H), 7.51 (d, J = 7.3 Hz, 2 H), 7.35–7.27 (m, 2 H), 7.27–7.21 (m,
1 H), 4.48 (d, J = 25.0 Hz, 1 H), 4.03–3.92 (m, 2 H), 3.88 (s, 3 H), 3.89–
3.79 (m, 2 H), 1.10 (q, J = 6.7 Hz, 6 H).
Ethyl (3-Methylphenyl)(4-cyanophenyl)acetate (4l)
Prepared according to general procedure A from 4-iodobenzonitrile
and (3-methylphenyl)diazoacetate. Reaction time 2 h.
13C{1H} NMR (100 MHz, CDCl3):  = 166.8, 142.2, 136.0, 129.8, 129.5,
129.4, 128.9, 128.7, 127.4, 62.9 (d, J = 6.7 Hz), 62.7 (d, J = 6.7 Hz), 52.1,
51.3 (d, J = 138.2 Hz), 16.2.
Yield: 89 mg (64%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.61 (d, J = 8.2 Hz, 2 H), 7.44 (d, J =
8.2 Hz, 2 H), 7.52–7.48 (m, 1 H), 7.46–7.40 (m, 3 H), 5.09 (s, 1 H), 4.24
(q, J = 7.1 Hz, 2 H), 3.91 (s, 3 H), 1.26 (t, J = 7.1 Hz, 3 H).
31P NMR (162 MHz, CDCl3):  = 24.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H24O5P: 363.1361; found:
363.1361.
13C{1H} NMR (100 MHz, CDCl3):  = 171.5, 144.1, 138.7, 137.3, 132.3,
129.4, 129.1, 128.8, 128.5, 125.4, 118.7, 111.1, 61.6, 56.9, 21.4, 14.1.
Diethyl (4-Cyanophenyl)(phenyl)methylphosphonate (6d)
IR (film): 2227, 1731, 1607 cm–1
.
Prepared according to general procedure B from 4-iodobenzonitrile
and diethyl 1-diazo-phenylmethylphosphonate.
Anal. Calcd for C18H17NO2: C, 77.40; H, 6.13; N, 5.01. Found: C, 77.18;
H, 5.94; N, 4.88.
Yield: 86 mg (63%); colorless oil.
1H NMR (400 MHz, CDCl3):  = 7.65 (d, J = 8.3 Hz, 2 H), 7.60 (d, J =
8.3 Hz, 2 H), 7.49 (d, J = 8.2 Hz, 2 H), 7.37–7.30 (m, 2 H), 7.30–7.24 (m,
1 H), 4.48 (d J = 25.1 Hz, 1 H,), 4.06–3.76 (m, 4 H), 1.14 (t, J = 7.0 Hz,
3 H), 1.09 (t, J = 7.0 Hz, 3 H).
Diethyl [4-(Methoxycarbonyl)phenyl](4-methoxyphenyl)methyl-
phosphonate (6a)
Prepared according to general procedure B from methyl 4-iodobenzo-
ate and diethyl 1-diazo-(4-methoxyphenyl)methylphosphonate.
13C{1H} NMR (100 MHz, CDCl3):  = 142.4, 135.4, 132.2, 130.1, 129.4,
128.8, 127.6, 118.6, 110.9, 63.1 (d, J = 6.6 Hz), 62.6 (d, J = 6.6 Hz), 51.2
(d, J = 138.9 Hz), 16.1.
Yield: 129 mg (66%); colorless oil.
31P NMR (162 MHz, CDCl3):  = 23.6.
© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–F

F
S. M. Golitsin et al.
Paper
Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C18H21NO3P: 330.1259; found:
330.1260.
References
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8.4 Hz, 2 H), 7.51 (d, J = 8.2 Hz, 2 H), 7.35–7.30 (m, 2 H), 7.28–7.23 (m,
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31P NMR (162 MHz, CDCl3):  = 24.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H24O4P: 347.1412; found:
347.1414.
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This work was supported by a Russian Science Foundation (grant 19-
13-00223).
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Acknowledgment
The research work was carried out with an Agilent 400-MR NMR
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© 2019. Thieme. All rights reserved. Synthesis 2019, 51, A–F