Synthesis 2020; 52(05): 775-780
DOI: 10.1055/s-0039-1690758
paper
© Georg Thieme Verlag Stuttgart · New York

Palladium-Catalyzed Hydroarylation of Diazocarboxylates and Diazophosphonates

Sergey M. Golitsin
,
Irina P. Beletskaya
,
Department of Chemistry, Moscow State University, 119991, Leninskie gory 1-3, Moscow, Russian Federation   Email: titanyuk@org.chem.msu.ru
› Author Affiliations
This work was supported by a Russian Science Foundation (grant 19-13-00223).
Further Information

Publication History

Received: 13 September 2019

Accepted after revision: 10 November 2019

Publication Date:
27 November 2019 (online)

 


Abstract

A simple synthetic procedure for the Pd-catalyzed hydro­arylation 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 71%.


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The transition-metal-catalyzed transformation of α-diazocarbonyl 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 nitriles 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 important 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]

Zoom Image
Scheme 1

In the latter case, a organopalladium intermediate that is generated can be captured with a nucleophile.[4] [5] [6] The hydride ion generated from formic acid is a suitable nucleo­phile for this type reaction. Our research group has elaborated Pd-catalyzed three-component hydroarylation coupling: aryl iodides reacted with α-diazocarboxylates/α-diazophosphonates and formic acid to generate mono- or diarylacetates and diarylphosphonates.

Recently, J. Wang and co-workers have reported Pd-catalyzed reductive coupling of ethyl diazoacetate (EDA) with aryl iodides leading to the formation of α,α-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 research team (Scheme [2]).[8]

Zoom Image
Scheme 2 Hydroarylation of EDA with aryl iodides[8]

A number of aryl iodides were subjected to three-component hydroarylation under the optimized reaction conditions. Exploration of substrates containing electron-withdrawing groups (EWG) as well as iodobenzene allowed a range of ethyl arylacetates 2 to be synthesized in respectable 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.

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 preparation of diarylated products (Table [1]).

Table 1 Optimization of the Reaction Conditions in the Model Reactiona

Entry

Catalyst

Base

Solvent

Yield (%)b

 1

PdCl2(PPh3)2

Et3N

MeCN

38

 2

Pd2dba3+PPh3

Et3N

MeCN

29

 3

PdCl2(PCy3)2

Et3N

MeCN

 0

 4

Pd(PPh3)4

Et3N

MeCN

42

 5

Pd(PPh3)4

Et3N

1,2-DCE

60

 6

Pd(PPh3)4

Et3N

benzene

42

 7

Pd(PPh3)4

Et3N

EtOH

traces

 8

Pd(PPh3)4

Et3N

THF

52

 9

Pd(PPh3)4

Et3N

CHCl3

20

10

PdCl2(PPh3)2

Et3N

1,2-DCE

70

11

PdCl2(PPh3)2

DBU

1,2-DCE

traces

12

PdCl2(PPh3)2

Py

1,2-DCE

20

13

PdCl2(PPh3)2

DIPEA

1,2-DCE

24

14

PdCl2(PPh3)2

K2CO3

1,2-DCE

30

15c

PdCl2(PPh3)2

Et3N

1,2-DCE

 0

16d

PdCl2(PPh3)2

Et3N

1,2-DCE

31

17e

PdCl2(PPh3)2

Et3N

1,2-DCE

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.

c Carried out at 20 °C.

d Carried out at 40 °C.

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 investigated 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. Triethylamine 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 investigated. Attempts to obtain hydroarylated product 4a at room temperature failed. Increase of reaction temperature greatly influenced the amount of synthesized product. In summary, it was found that the most favorable conditions were: 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 α-aryldiazoacetates 3 in the presence of formic acid and triethylamine provided diarylacetates 4al in a yield up to 71% (Table [2]). The scope of the proposed method was examined by application of ethyl α-aryldiazocarboxylates (3ad) in the hydroarylation reaction with a series of aryl iodides 1 under the optimized reaction conditions.

Table 2 Hydroarylation of α-Aryldiazoacetates 3 with Aryl Iodides 1 a

Entry

R

Ar

Product

Yield (%)b

 1

H (3a)

p-MeO2CC6H4 (1a)

4a

70

 2

H (3a)

m-MeO2CC6H4 (1b)

4b

45

 3

H (3a)

3-C5H4N (1c)

4c

53

 4

H (3a)

p-NCC6H4 (1d)

4d

66

 5

H (3a)

p-O2NC6H4 (1e)

4e

71

 6

H (3a)

p-F3CC6H4 (1f)

4f

55

 7

H (3a)

p-AcC6H4 (1g)

4g

69

 8

H (3a)

m-MeC6H4 (1h)

4h

trace

 9

p-CN (3b)

p-O2NC6H4 (1e)

4i

37

10

p-CN (3b)

m-MeO2CC6H4 (1b)

4j

35

11

p-MeO2C(3c)

p-MeO2CC6H4 (1a)

4k

43

12

m-Me (3d)

p-NCC6H4 (1d)

4l

64

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.

Exploration of EWG-containing aryl iodides and 3-iodopyridine allowed phenylarylacetates 4ag to be synthesized in good yields (40–71%). Aryl iodide containing electron-donating groups (m-tolyl iodide) exhibited poor reactivity 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).

The phosphonate (PO3 2–) moiety is a common structural fragment that is present in a wide range of biologically active­ compounds.[9] [10] Despite structural and electronic differences between phosphonate and carboxylic functionalities (in terms of size, shape, acidity, and geometry) the phosphonate­ functionality is regarded as a bioisostere of the carboxylic group. α-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 6ae (Table [3]). Diazophosphonates 5 exhibited comparable reactivity under analogous reaction conditions yielding the corresponding α,α-diarylphosphonates 6ae in good yield.

Table 3 Hydroarylation of Diazophosphonates 5 with Aryl Iodides 1 a

Entry

R1

R

Product

Yield (%)b

1

p-MeO (5a)

p-MeO2C

6a

66

2

H (5b)

p-O2N

6b

60

3

H (5b)

p-MeO2C

6c

54

4

H (5b)

p-NC

6d

63

5

H (5b)

p-Ac

6e

71

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 presented in Scheme [3]. Palladium dichloride complex can be easily reduced by formic acid resulting in Pd(0) species. The catalytic cycle starts with oxidative addition to form arylpalladium iodide complex A. Then addition of diazo compound to this complex could generate carbene complex B.[12] Migration of the aryl group to the carbene center, which is now described in several publications,[13] [14] would produce benzylic 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). Reductive elimination should provide the product simultaneously with regeneration of the Pd(0) species.

Zoom Image
Scheme 3 Mechanism of hydroarylation

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 preparation of diarylated carboxylic acid and phosphonic acid derivatives that are otherwise difficult to access. A range of arylated products were synthesized in 35–71% yield by applying this methodology.

All solvents were distilled prior to use. Acetonitrile and 1,2-dichloroethane 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 tetramethylsilane with the solvent resonance as the internal standard (CDCl3, δ = 7.26 ppm). 13C{1H} NMR spectra were collected with commercial Agilent 400-MR (100 MHz) instrument with complete proton decoupling. 31P and 19F NMR spectra were recorded with a commercial Agilent 400-MR (162 MHz and 376 MHz respectively) instrument. HRMS (ESI) were recorded with a commercial apparatus. Published procedures were applied for the synthesis of aryldiazocarboxylates (3)[3a] and aryldiazophosphonates (5).[3b]


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Pd-Catalyzed Cross-Coupling between Aryl Iodides and Aryldiazoacetates; Typical Procedure A

To a mixture of aryl iodide (1ah; 0.5 mmol), aryldiazoacetate (3ad; 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 1ah 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).


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Pd-Catalyzed Cross-Coupling between Aryl Iodides and Aryldiazophosphonates; Typical Procedure B

To a mixture of aryl iodide 1 (0.5 mmol), aryldiazophosphonate (5ab; 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).


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Characterization of Synthesized Products


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Ethyl [4-(Methoxycarbonyl)phenyl](phenyl)acetate (4a)

Prepared according to general procedure A from methyl 4-iodobenzoate and phenyldiazoacetate. Reaction time 2 h.

Yield: 104 mg (70%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 171.9, 166.8, 143.8, 138.0, 129.8, 129.2, 128.7, 128.5, 127.5, 127.2, 61.4, 57.1, 52.1, 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]


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Ethyl [3-(Methoxycarbonyl)phenyl](phenyl)acetate (4b)

Prepared according to general procedure A from methyl 3-iodobenzoate and phenyldiazoacetate. Reaction time 2.5 h.

Yield: 67 mg (45%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 8.02 (bs, 1 H), 7.95 (dt, 1 J = 7.7 Hz, 2 J = 1.3 Hz, 1 H), 7.53 (dt, 1 J = 7.7 Hz, 2 J = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 172.1, 166.8, 139.2, 138.3, 133.1, 130.5, 129.8, 128.9, 128.7, 128.6, 128.3, 127.5, 61.4, 56.9, 52.1, 14.1.

IR (film): 1740, 1610, 1281 cm–1.

HRMS (ESI): m/z [M + H]+ calcd for C18H18O4: 299.1283; found: 299.1278.


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Ethyl (Pyridin-3-yl)(phenyl)acetate (4c)

Prepared according to general procedure A from 3-iodopyridine and phenyldiazoacetate. Reaction time 2.5 h.

Yield: 64 mg (53%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 8.57 (d, J = 2.0 Hz, 1 H), 8.50 (dd, 1 J = 4.7 Hz, 2 J = 1.5 Hz, 1 H), 7.68 (dt, 1 J = 1.7 Hz, 2 J = 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): δ = 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.

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.

NMR spectral data for this compound were consistent with those in the literature.[15]


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Ethyl (4-Cyanophenyl)(phenyl)acetate (4d)

Prepared according to general procedure A from 4-iodobenzonitrile and phenyldiazoacetate. Reaction time 2 h.

Yield: 87 mg (66%); yellow oil.

1H NMR (400 MHz, CDCl3): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 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.

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.

NMR spectral data for this compound were consistent with those in the literature.[7]


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Ethyl (4-Nitrophenyl)(phenyl)acetate (4e)

Prepared according to general procedure A from 4-iodo-1-nitrobenzene and phenyldiazoacetate. Reaction time 1.5 h.

Yield: 100 mg (71%); yellow oil.

1H NMR (400 MHz, CDCl3): δ = 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): δ = 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): 1735, 1520, 1355 cm–1.

Anal. Calcd for C16H15NO4: C, 67.36; H, 5.30; N, 4.91. Found: C, 67.49; H, 5.31; N, 4.86.

NMR spectral data for this compound were consistent with those in the literature.[7]


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Ethyl [4-(Trifluoromethyl)phenyl](phenyl)acetate (4f)

Prepared according to general procedure A from 4-trifluoromethyl-1-iodobenzene and phenyldiazoacetate. Reaction time 3 h.

Yield: 85 mg (55%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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): δ = 171.8, 142.7, 137.9, 129.0, 128.8, 128.7 (q, J C–F = 33.4 Hz), 128.5, 127.6, 125.5 (q, J C–F = 3.8 Hz), 123.9 (q, J C–F = 244 Hz, CF3), 61.5, 56.8, 14.1.

19F NMR (376 MHz, CDCl3): δ = 62.6.

Anal. Calcd for C17H15F3O2: C, 66.23; H, 4.90. Found: C, 66.31; H, 5.01.


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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): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 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.

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]


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Ethyl (4-Nitrophenyl)(4-cyanophenyl)acetate (4i)

Prepared according to general procedure A from 4-iodo-1-nitrobenzene and (4-cyanophenyl)diazoacetate. Reaction time 3 h.

Yield: 57 mg (37%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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): δ = 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.

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.


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Ethyl [3-(Methoxycarbonyl)phenyl](4-cyanophenyl)acetate (4j)

Prepared according to general procedure A from methyl 3-iodobenzoate and (4-cyanophenyl)diazoacetate. Reaction time 4 h.

Yield: 56 mg (35%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 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.

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.


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Ethyl Bis[4-(methoxycarbonyl)phenyl]acetate (4k)

Prepared according to general procedure A from methyl 4-iodobenzoate and (4-(methoxycarbonyl)phenyl)diazoacetate. Reaction time 2 h.

Yield: 76 mg (43%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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): δ = 171.2, 166.6, 142.9, 129.9, 129.4, 128.6, 61.6, 56.9, 52.1, 14.1.

IR (film): 1725, 1610, 1280 cm–1.

Anal. Calcd for C20H20O6: C, 67.41; H, 5.66. Found: C, 67.44; H, 5.69.

NMR spectral data for this compound were consistent with those in the literature.[7]


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Ethyl (3-Methylphenyl)(4-cyanophenyl)acetate (4l)

Prepared according to general procedure A from 4-iodobenzonitrile and (3-methylphenyl)diazoacetate. Reaction time 2 h.

Yield: 89 mg (64%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 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.

IR (film): 2227, 1731, 1607 cm–1.

Anal. Calcd for C18H17NO2: C, 77.40; H, 6.13; N, 5.01. Found: C, 77.18; H, 5.94; N, 4.88.


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Diethyl [4-(Methoxycarbonyl)phenyl](4-methoxyphenyl)methylphosphonate (6a)

Prepared according to general procedure B from methyl 4-iodobenzoate and diethyl 1-diazo-(4-methoxyphenyl)methylphosphonate.

Yield: 129 mg (66%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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): δ = 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.

31P NMR (162 MHz, CDCl3): δ = 24.5.

Anal. Calcd for C20H25O6P: C, 61.22; H, 6.42. Found: C, 61.18; H, 6.49.


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Diethyl (4-Nitrophenyl)(phenyl)methylphosphonate (6b)

Prepared according to general procedure B from 4-iodo-1-nitrobenzene and diethyl 1-diazo-phenylmethylphosphonate.

Yield: 104 mg (60%); yellow oil.

1H NMR (400 MHz, CDCl3): δ = 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): δ = 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.

31P NMR (162 MHz, CDCl3): δ = 23.4.

Anal. Calcd for C17H20NO5P: C, 58.45; H, 5.77; N, 4.01. Found: C, 58.28; H, 5.69; N, 4.09.

NMR spectral data for this compound were consistent with those in the literature.[17]


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Diethyl [4-(Methoxycarbonyl)phenyl](phenyl)methylphosphonate (6c)

Prepared according to general procedure B from methyl 4-iodobenzoate and diethyl 1-diazo-phenylmethylphosphonate.

Yield: 97 mg (54%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 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.

31P NMR (162 MHz, CDCl3): δ = 24.2.

HRMS (ESI): m/z [M + H]+ calcd for C19H24O5P: 363.1361; found: 363.1361.


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Diethyl (4-Cyanophenyl)(phenyl)methylphosphonate (6d)

Prepared according to general procedure B from 4-iodobenzonitrile and diethyl 1-diazo-phenylmethylphosphonate.

Yield: 86 mg (63%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 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).

13C{1H} NMR (100 MHz, CDCl3): δ = 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.

31P NMR (162 MHz, CDCl3): δ = 23.6.

HRMS (ESI): m/z [M + H]+ calcd for C18H21NO3P: 330.1259; found: 330.1260.


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Diethyl (4-Acetylphenyl)(phenyl)methylphosphonate (6e)

Prepared according to general procedure B from 4-iodoacetophenone and diethyl 1-diazo-phenylmethylphosphonate.

Yield: 100 mg (71%); colorless oil.

1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.2 Hz, 2 H), 7.63 (d, J = 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, 1 H), 4.49 (d, J = 25.0 Hz, 1 H), 4.03–3.93 (m, 2 H), 3.92–3.77 (m, 2 H), 2.57 (s, 3 H), 1.13 (t, J = 7.1 Hz, 3 H), 1.10 (t, J = 7.1 Hz, 3 H).

13C{1H} NMR (100 MHz, CDCl3): δ = 197.6, 142.3, 135.8, 129.6, 129.4, 129.3, 128.7, 128.5, 127.4, 62.9 (d, J = 6.6 Hz), 62.6 (d, J = 6.6 Hz), 51.2 (d, J = 138.4 Hz), 26.5, 16.1.

31P NMR (162 MHz, CDCl3): δ = 24.2.

HRMS (ESI): m/z [M + H]+ calcd for C19H24O4P: 347.1412; found: 347.1414.


#
#

Acknowledgment

The research work was carried out with an Agilent 400-MR NMR spectrometer purchased under the program of MSU development. The authors would like to acknowledge Thermo Fisher Scientific Inc., MS Analytica (Moscow, Russia), and personally to Prof. Alexander Makarov for providing mass spectrometry equipment for this work.

Supporting Information

  • References


    • For some recent reviews, see:
    • 1a Ford A, Miel H, Ring A, Slattery CN, Maguire AR, McKervey MA. Chem. Rev. 2015; 115: 9981
    • 1b Zhang Z, Wang J. Tetrahedron 2008; 64: 6577
    • 1c Doyle MP, Duffy R, Ratnikov M, Zhou L. Chem. Rev. 2010; 110: 704
    • 1d Li Y.-P, Li Z.-Q, Zhu S.-F. Tetrahedron Lett. 2018; 59: 2307

      For recent publications, see:
    • 2a Zhang Y, Wang J. Eur. J. Org. Chem. 2011; 1015
    • 2b Zhang Y, Wang J. Chem. Commun. 2009; 5350
    • 2c Liu Z, Huo J, Fu T, Tan H, Ye F, Hossain ML, Wang J. Chem. Commun. 2018; 54: 11419
    • 3a Peng C, Cheng J, Wang J. J. Am. Chem. Soc. 2007; 129: 8708
    • 3b Kosobokov MD, Titanyuk ID, Beletskaya IP. Tetrahedron Lett. 2014; 55: 6791
    • 4a Devine SK. J, Van Vranken DL. Org. Lett. 2007; 9: 2047
    • 4b Devine SK. J, Van Vranken DL. Org. Lett. 2008; 10: 1909
    • 4c Kadirka R, Devine SK. J, Adams CS, Van Vranken DL. Angew. Chem. Int. Ed. 2009; 48: 3677
  • 5 Zhang Z, Liu Y, Gong M, Zhao X, Zhang Y, Wang J. Angew. Chem. Int. Ed. 2010; 49: 1139
  • 6 Santi M, Ould DM. C, Wenz J, Soltani Y, Melen RL, Wirth T. Angew. Chem. Int. Ed. 2019; 58: 7861
  • 7 Ye F, Qu S, Zhou L, Peng C, Wang C, Cheng J, Hossain ML, Liu Y, Zhang Y, Wang Z, Wang J. J. Am. Chem. Soc. 2015; 137: 4435
  • 8 Titanyuk ID, Beletskaya IP. Synlett 2013; 24: 355
  • 9 Heaney LF. In Comprehensive Organic Functional Group Transformations, Vol. 4. Katritzky AR, Meth-Kohn O, Rees CW. Elsevier Science; Oxford: 1995. Chap. 4.10, 451-504
  • 10 Filler R, Kobayashi Y, Yagupolski LM. In Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications . Elsevier Science; Amsterdam: 1999
  • 11 Marinozzi M, Pertusati F, Serpi M. Chem. Rev. 2016; 116: 13991
  • 12 Broering M, Brandt CD, Stellwag S. Chem. Commun. 2003; 2344
  • 13 Albeniz AC, Espinet P, Manrique R, Perez-Mateo A. Angew. Chem. Int. Ed. 2002; 41: 2363
  • 14 Sole D, Vallverdu L, Solans X, Font-Bardia M, Bonjoch J. Organometallics 2004; 23: 1438
  • 15 Ke J, He C, Liu H, Xu H, Lei A. Chem. Commun. 2013; 49: 6767
  • 16 Xia Y, Liu Z, Feng S, Ye F, Zhang Y, Wang J. Org. Lett. 2015; 17: 956
  • 17 Makosza M, Sulikowski D. J. Org. Chem. 2009; 74: 3827

  • References


    • For some recent reviews, see:
    • 1a Ford A, Miel H, Ring A, Slattery CN, Maguire AR, McKervey MA. Chem. Rev. 2015; 115: 9981
    • 1b Zhang Z, Wang J. Tetrahedron 2008; 64: 6577
    • 1c Doyle MP, Duffy R, Ratnikov M, Zhou L. Chem. Rev. 2010; 110: 704
    • 1d Li Y.-P, Li Z.-Q, Zhu S.-F. Tetrahedron Lett. 2018; 59: 2307

      For recent publications, see:
    • 2a Zhang Y, Wang J. Eur. J. Org. Chem. 2011; 1015
    • 2b Zhang Y, Wang J. Chem. Commun. 2009; 5350
    • 2c Liu Z, Huo J, Fu T, Tan H, Ye F, Hossain ML, Wang J. Chem. Commun. 2018; 54: 11419
    • 3a Peng C, Cheng J, Wang J. J. Am. Chem. Soc. 2007; 129: 8708
    • 3b Kosobokov MD, Titanyuk ID, Beletskaya IP. Tetrahedron Lett. 2014; 55: 6791
    • 4a Devine SK. J, Van Vranken DL. Org. Lett. 2007; 9: 2047
    • 4b Devine SK. J, Van Vranken DL. Org. Lett. 2008; 10: 1909
    • 4c Kadirka R, Devine SK. J, Adams CS, Van Vranken DL. Angew. Chem. Int. Ed. 2009; 48: 3677
  • 5 Zhang Z, Liu Y, Gong M, Zhao X, Zhang Y, Wang J. Angew. Chem. Int. Ed. 2010; 49: 1139
  • 6 Santi M, Ould DM. C, Wenz J, Soltani Y, Melen RL, Wirth T. Angew. Chem. Int. Ed. 2019; 58: 7861
  • 7 Ye F, Qu S, Zhou L, Peng C, Wang C, Cheng J, Hossain ML, Liu Y, Zhang Y, Wang Z, Wang J. J. Am. Chem. Soc. 2015; 137: 4435
  • 8 Titanyuk ID, Beletskaya IP. Synlett 2013; 24: 355
  • 9 Heaney LF. In Comprehensive Organic Functional Group Transformations, Vol. 4. Katritzky AR, Meth-Kohn O, Rees CW. Elsevier Science; Oxford: 1995. Chap. 4.10, 451-504
  • 10 Filler R, Kobayashi Y, Yagupolski LM. In Organofluorine Compounds in Medicinal Chemistry and Biomedical Applications . Elsevier Science; Amsterdam: 1999
  • 11 Marinozzi M, Pertusati F, Serpi M. Chem. Rev. 2016; 116: 13991
  • 12 Broering M, Brandt CD, Stellwag S. Chem. Commun. 2003; 2344
  • 13 Albeniz AC, Espinet P, Manrique R, Perez-Mateo A. Angew. Chem. Int. Ed. 2002; 41: 2363
  • 14 Sole D, Vallverdu L, Solans X, Font-Bardia M, Bonjoch J. Organometallics 2004; 23: 1438
  • 15 Ke J, He C, Liu H, Xu H, Lei A. Chem. Commun. 2013; 49: 6767
  • 16 Xia Y, Liu Z, Feng S, Ye F, Zhang Y, Wang J. Org. Lett. 2015; 17: 956
  • 17 Makosza M, Sulikowski D. J. Org. Chem. 2009; 74: 3827

Zoom Image
Scheme 1
Zoom Image
Scheme 2 Hydroarylation of EDA with aryl iodides[8]
Zoom Image
Scheme 3 Mechanism of hydroarylation