Cobalt catalyzed C-P bond formation by cross-coupling of boronic acids with P(O)H compounds in presence of zinc

Article abstract of DOI:10.3390/molecules25020290

In our current work, we have reported the first cobalt-catalyzed cross-coupling of arylboronic acid with alkyl/aryl phosphites under mild conditions. The reaction was carried out in the presence of zinc powder as an additive and ter-pyridine as a ligand. The use of non-precious cobalt salt makes the protocol advantageous, as it is inexpensive and more abundant than the previously used methods where precious metal salts (Pd and Pt) were used. The reaction has a wide substrate scope and the products were obtained in good yields.

Full text of DOI:10.3390/molecules25020290

molecules
Article
Cobalt Catalyzed C-P Bond Formation by
Cross-Coupling of Boronic Acids with P(O)H
Compounds in Presence of Zinc
Ian Hicks, Jonathan McTague, Tatiana Hapatsha, Rania Teriak and Parminder Kaur *
Department of Chemistry, College of Science and Health, William Paterson University, 300 Pompton Road,
Wayne, NJ 07470, USA; hicksi1@student.wpunj.edu (I.H.); mctaguej@student.wpunj.edu (J.M.);
hapatshat@student.wpunj.edu (T.H.); teriakr@yahoo.com (R.T.)
*
Correspondence: kaurp6@wpunj.edu; Tel.: +1-973-720-2706
ꢀ
ꢁꢂꢀꢃꢄꢅꢆꢇ
ꢀ
ꢁꢂꢃꢄꢅꢆ
Received: 22 September 2019; Accepted: 11 December 2019; Published: 10 January 2020
Abstract: In our current work, we have reported the first cobalt-catalyzed cross-coupling of arylboronic
acid with alkyl/aryl phosphites under mild conditions. The reaction was carried out in the presence
of zinc powder as an additive and ter-pyridine as a ligand. The use of non-precious cobalt salt makes
the protocol advantageous, as it is inexpensive and more abundant than the previously used methods
where precious metal salts (Pd and Pt) were used. The reaction has a wide substrate scope and the
products were obtained in good yields.
Keywords: cross-coupling reactions; terpyridine; arylboronic acid; alkyl/aryl phosphonates;
tridendate ligand
1
. Introduction
Organophosphorus compounds have great significance due to their extensive use in various
fields such as medicine, agriculture, polymer science, and material chemistry [
application of organophosphorus compounds varies from their use as catalysts in various organic
transformations, to being important additives in lubricants [ ]. Organophosphorus compounds are
also important building blocks for nucleic acid chemistry and are associated with increased biological
activity due to the presence of the C-P bond [ 11]. Hence, there is growing interest in developing new
methodologies for the synthesis of the C-P bond. In addition to the classical methods documented in
the literature [12 25], several new transition-metal-catalyzed approaches have been developed, mainly
for the synthesis of triarylphosphine compounds via cross-coupling reactions of trialkylphosphine with
different aryl sources in the presence of metals such as Ni-, Cu-, and Pd. [13 15] Among the various
1–25]. The wide
5,6
1–
–
–
aryl partners, arylboronic acid is a popular choice for various C-C and C-heteroatom bond formation
reactions via different cross-coupling methodologies. However, despite the extensive use of arylboronic
acid in a variety of other cross-coupling reactions [26–28], it has not been used quite as often in the
literature for the C-P bond formation and only a couple of reports have been published so far. In 2008,
Stawinski and his group published one of the first palladium-catalyzed cross-coupling reactions of
aryl boronic acid with dialkyl phosphites [29]. The method showed a moderate to good yield of the
product, but the substrate scope was limited. Moreover, the reaction was done under microwave
irradiation in the presence of DMF as solvent and p-benzoquinone as oxidant. More recently, Zhao
et al. reported a copper-catalyzed Chan–Lam-type reaction of arylboronic acid with H-phosphonate
diesters. This reaction was carried out in the presence of 1,10-phenanthroline as the ligand. However,
while the reaction resulted in moderate to high yields of the products, it was still limited to certain
dialkyl phosphites. Only a poor reaction yield was observed with the dibenzyl phosphite [30]. Most
Molecules 2020, 25, 290; doi:10.3390/molecules25020290
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of the reactions were reported with diethyl phosphite, and some of these reactions suffered poor
product yields. Additionally, the protocol requires the use of ligand (1,10-phenanthroline) for the
catalysis [30]. Later, Zhao et al. reported the nickel-catalyzed cross-coupling of arylboronic acid with
secondary phosphine oxide for the synthesis of triarylphosphine oxides [31]. While moderate to high
yields of the products were obtained, the reaction was performed under high catalyst loadings, as
◦
well as elevated temperature (100 C). Hence, it is of great interest to find an efficient, inexpensive,
and more versatile, non-precious metal-based catalytic system for the synthesis of valuable C-P bond
formation. Among other metals, cobalt has been widely used as a highly efficient metal for various
C-C and C-N cross-coupling reactions, as reported by Gosmini, Oshima, and others [32
been found, in the literature, that the cobalt-catalyzed reactions were more specific compared to their
Pd and Ni counterparts [32 35]. Moreover, it is evident in the literature that the cobalt-catalyzed
cross-coupling reactions followed an alternative mechanism. For example, the oxidative coupling for
the cobalt-catalyzed reaction occurred through a single-electron transfer [36 37], hence avoiding the
–34]. It has
–
,
side reactions that are commonly observed in the Pd and Ni-catalyzed reactions. Hence, high efficiency,
cost effectiveness, and milder reaction conditions makes cobalt-catalyzed reactions a powerful tool
for C-C and C-heteroatom bond formation. Additionally, our group focuses on exploring a simpler
catalytic system for organic transformation [38]; in our continuing effort, a series of simpler ligands
were also tested during the optimization of C-P bond formation in the current work.
In the present work, we are pleased to disclose a simple, inexpensive, and efficient method for the
synthesis of aryl phosphonates. The reaction has been performed in the presence of cobalt salt and
zinc metal under mild reaction conditions in the presence of ter-pyridine as the ligand. To the best of
our knowledge, this is the first cobalt-catalyzed C-P bond formation report so far.
2
. Result and Discussion
Initially, we optimized the reaction by choosing a cobalt-based catalytic system for the
cross-coupling reaction of phenylboronic acid with diethyl phosphite. The test reaction was carried
out with CoCl (8 mol%) in the presence of Cs CO (1 equiv) and ligand (10 mol%) in acetonitrile at
1
2
2
3
room temperature. No inert atmosphere was maintained while carrying out the reaction. The reaction
proceeded with a poor yield (36%) and no further improvement was observed by increasing the
reaction time up to 24 h. However, it was promising to see that the product formation was taking
◦
place. The reaction was also exposed to higher temperatures, ranging from 50 to 78 C, but no increase
in yield was observed. We then continued the screening of different bases such as K CO , Et N, and
2
3
3
DIPEA (entries 1–5, Table 1), but not much improvement was observed. However, when Zn powder
1 equiv) was added to the reaction, a drastic improvement in the yields was observed (entry 2 vs.
(
entry 4, Table 1). We then continued to screen other cobalt-catalyst and ligands to optimize the reaction
conditions further. The effect of different cobalt salts and ligands has been summarized in Table 1. It
was found that the reaction proceeded with a good yield (84%, entry 12, Table 1) with cobalt (II) iodide
(
8 mol%) as the catalyst in the presence of zinc powder, and ligand 4. When Co(NO ) was used as the
3 2
catalyst (entry 11, Table 1), the reaction yield dropped to 61%. The use of Co(OAc) did not improve
2
the reaction yield either (entry 13, Table 1) and only 56% of the cross-coupling product was obtained.
When Co(acac) was used to carry out the reaction, 63% of the product was obtained.
2

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Table 1. Optimization of the reaction conditions a.
Entry
Ligand
Cobalt Source
Additive
Base
Cs CO
Yield%
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
2
3
4
5
4
4
4
4
4
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
CoCl2
Co(NO3)2
CoI2
Co(OAc)2
CoBr2
-
-
19
32
34
38
44
42
56
65
79
60
61
84
56
91
63
2
3
K CO
2 3
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
Zn
DIPEA
K CO
2
3
Et N
3
-
-
-
-
-
-
-
-
-
-
1
0
1
2
3
4
5
1
1
1
1
1
Co(acac)2
a
All reactions were carried out at room temperature with Boronic acid (0.20 mmol), Co salt (8 mol%), ligand
10 mol%), additive (20 mol%), and dialkylphosphite (0.20 mmol) in dry acetonitrile for 24 h.
(
However, when the reaction was carried out with cobalt (II) bromide (8 mol%), as the catalyst in
the presence of zinc powder and ligand 4, an excellent yield (91%) was obtained (entry 14, Table 1).
It was also found that the reaction gave poor yields in the absence of zinc powder. We have also
screened various ligands (entry 6–10, Table 1) and it was found that the presence of ter-pyridine (ligand
4
, entry 9, Table 1) effectively influenced the reaction outcome. The presence of a ligand increased
the reaction yield significantly, as compared to the yield with no ligand. The reaction only worked
moderately well when pyridine (ligand
1
), 2-picolylamine (ligand
2
), di-(2-picolyl)amine (ligand
3
),
0
and 2,2 -dipyridylamine (ligand
5) were used as ligands (as shown in Table 2), which clearly shows
the crucial role of the ligand in this catalytic system. The reaction was also carried out with different
catalyst loadings and it was found that the reaction worked best with 8 mol% of CoBr . Further, a
2
decrease in the catalyst loading adversely affected the reaction profile. For further optimizations, the
effect of solvents on the reaction was observed, and after screening solvents such as THF, toluene,
dimethylformamide, and 1,4-dioxane, acetonitrile, it was found that the reaction worked best with
toluene as the solvent.
Table 2. Screening of various ligands for the C-P bond formation reaction a.
Entry
Ligand
% Yield
1
2
3
4
5
Pyridine (ligand 1)
2-picolylamine (ligand 2)
di-(2-picolyl)amine (ligand 3)
ter-pyridine (ligand 4)
54
56
65
79
60
0
2,2 -dipyridylamine (ligand 5)
a
All reactions were carried out at room temperature with Boronic acid (0.20 mmol), Co salt (8 mol%), ligand
10 mol%), additive (20 mol%), and dialkylphosphite (0.20 mmol) in dry acetonitrile for 24 h.
(
With these optimized conditions in hand, the substrate scope for this reaction was tested by
reacting a variety of arylboronic acids with diethyl phosphite. The reaction was carried out with

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boronic acid (0.20 mmol) reacting with diethyl phosphite (0.20 mmol) in the presence of 8 mol% of the
cobalt-catalyst, ter-pyridine (10 mol%), and zinc powder (20 mol%).
The effect of different groups on the arylboronic acid has been screened (Table 3) and it was found
that both the presence of the electron-withdrawing group, as well as the electron-donating group,
worked efficiently under the optimized reaction conditions. The presence of the trifluoromethyl group
on the boronic acid decreased the reaction yield significantly (entry 9, Table 3). In the presence of
ortho-substitutent, the reaction worked very well, with high yields in almost all cases (entries 2 and 7,
Table 3). The reaction had good tolerance with a variety of functional group such as methoxy, nitro,
and trifloromethyl (entries 3, 5, and 9, Table 3).
Table 3. Substrate scope for the cross-coupling reaction between boronic acids (6a–6j) and diethyl
phosphite (7b) a.
Entry
R
Product
Yield%
1
2
3
4
5
6
7
8
9
H (6a)
2-methyl (6b)
4-methoxy (6c)
4-ethynyl (6d)
3-nitro (6e)
8a
8b
8c
8d
8e
8f
8g
8h
8i
91
89
87
78
66
65
82
63
45
76
74
68
57
4-fluoro (6f)
2-fluoro (6g)
2,6-difluoro (6h)
4-trifluoromethyl (6i)
1-Naphthyl (6j)
4-nitro (6k)
10
11
12
13
8j
8k
8l
4-cyano (6l)
4-pyridyl (6m)
8m
a
All reactions were carried out at room temperature with aldehyde (0.20 mmol), Co salt (8 mol%), ligand (10 mol%),
Zn powder (20 mol%), and dialkylphosphite (0.20 mmol) in dry acetonitrile for 24 h.
After screening various boronic acids, a series of dialkyl/diaryl phosphites were also tested to see
the scope of the reaction under the same optimized reaction conditions (Table 4). Additionally, we
were pleased to find that the reaction worked very well with all the phosphite derivatives. The yields
were high in alkyl and aryl phosphites. Diphenyl and dibenzyl phosphite gave good yields with
the arylboronic acid, unlike copper-catalyzed reaction, where dibenzyl phosphonate ester resulted in
moderate to poor yields [13].

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Table 4. Results of screening different dialkyl/diaryl phosphites a.
0
Entry
R
R
Product
Yield%
1
2
3
4
5
6
7
8
9
H (6a)
4-methoxy (6c)
3-nitro (6e)
H (6a)
4-methoxy (6c)
3-nitro (6e)
H (6a)
4-methoxy (6c)
3-nitro (6e)
H (6a)
4-methoxy (6c)
3-nitro (6e)
Me (7a)
Me (7a)
Me (7a)
iPr (7c)
iPr (7c)
iPr (7c)
Ph (7d)
Ph (7d)
Ph (7d)
Bn (7e)
Bn (7e)
Bn (7e)
Bn (7e)
9a
9b
9c
79
78
81
79
62
71
84
74
56
89
78
67
59
10a
10b
10c
11a
11b
11c
12a
12b
12c
12d
1
0
1
2
3
1
1
1
4-trifluoro(methyl) (6i)
a
All reactions were carried out at room temperature with aldehyde (0.20 mmol), Co salt (8 mol%), ligand (10 mol%),
Zn powder (20 mol%), and dialkylphosphite (0.20 mmol) in dry acetonitrile for 24 h.
A plausible mechanism has been proposed in Scheme 1. While an elaborated study is required
to fully understand the mechanism of the reported methodology, it is anticipated [39] that the active
catalyst was generated when cobalt (II) salt was generated in the presence of the zinc powder and
ligand
dialkyl phosphite (
the formation of intermediate
formation of intermediate . Finally, the C-P bond forms by reductive elimination, which leads to the
regeneration of active catalyst . Alternatively, the addition of arylboronic acid to Co(0) in order to
4
. It is also anticipated that the active catalyst
) to generate the intermediate , which, upon reaction with boronic acid, leads to
. The elimination of boronic acid from intermediate then leads to the
A then undergoes oxidative addition with the
B
C
D
D
E
A
give Co(II) might be a possibility, which will be followed by transmetallation with the deprotonated
phoshite, and finally, the reductive elimination leads to the formation of the cross-coupling product [31].

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Scheme 1. Proposed mechanism for the Co-Zn catalyzed cross-coupling.
. Materials and Methods
.1. General Information
3
3
All experiments were carried out using dry solvents. The boronic acid, dialkyl phosphites, DIPEA,
0
triethylamine, pyridine, 2,2 -dipyridylamine, 2-picolylamine, di-(2-picolyl)amine, and ter-pyridine, as
well as the cobalt salts, were purchased from Sigma Aldrich. Silica gel for column chromatography
and thin layer chromatography (TLC) plates (Silica gel 60 F254) were ordered from EMD/Merck.
The analytical thin layer chromatography was eluted in the Ethylacetate/Hexane (30:70) solvent system.
An ultra-violet lamp, iodine chamber, and PMA solution spray was used to visualize the product
1
13
spots on thin layer chromatography (TLC). H-NMR and C-NMR spectra were recorded on Bruker
1
Advance 400 and 100 MHz, respectively, and were referenced to residual protic solvent (CDCl3 H
7.26 ppm] and CDCl3 13C [77.00 ppm]. Mass analyses were performed on the Joel GC-MS instrument
EI). The products were fully characterized using H-NMR, C-NMR, P-NMR, and GC-MS, and the
[
1
13
31
(
relevant data has been provided in this section. All reagents were used as received from commercial
sources without further purification.
3
.2. General Procedure for the Synthesis of Aryl Phosphonates
The phenyl boronic acid (6a, 0.20 mmol) was added to a 25 mL round bottom flask (oven-dried
overnight), followed by the addition of the cobalt (II) bromide (8 mol%), ter-pyridine (ligand
4,
1
0 mol%), and zinc powder (20 mol%). At this point the solvent, dry acetonitrile (6 mL), was added
to the reaction mixture, followed by the addition of diethyl phosphite (7b, 0.20 mmol) which was
added sequentially. The reaction vessel was covered with the septum and the reaction was stirred at
room temperature. The reaction was allowed to run for 24 h at the same temperature. At this time,
the reaction progress was monitored using TLC. The reaction was monitored at 4 h intervals and
was ultimately left stirring at room temperature overnight. After completion, the reaction mixture
was quenched and extracted with ethyl acetate and water. The organic layer was collected, and the
aqueous layer was again extracted with ethyl acetate three more times. The combined organic layer

Molecules 2020, 25, 290
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was further washed with sodium bicarbonate and brine solution. The organic layer was then dried
over sodium sulfate, and filtered and evaporated using rotavap. The crude compound obtained was
further purified using column chromatography (EA:hexane 30:70). The pure product (8a) was obtained
as thick oil with a 91% yield. The 1-H and 13-C data for the products obtained matched those reported
previously [29,40,41].
3
.2.1. Compound 8a: Diethyl Phenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.54 (d, J = 7.0 Hz, 2H), 7.39 (t, J = 7.2 Hz, 2H), 7.32 (t, J = 7.0 Hz,
H), 4.22 (m, 4H, CH2), 1.62 (td, JCH3-CH2 = 7.2 Hz, JCH3P = 1.0 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
δ
1
1
δ
31.6 (d, J = 3.0 Hz, C4), 130.9 (d, J = 8.0 Hz, 2C), 128.4 (d, J = 14.0 Hz, 2C), 125.1 (d, J = 178.4 Hz, C1),
+
6
4.3 (d, JCH2 = 7.8 Hz, 2C), and 18.1 (d, JCH3 = 6.4 Hz, 2C). GC-MS m/z: [M + H] Calcd for C H O P
10
16
3
2
15.0832; Found 215.0815.
3
.2.2. Compound 8b: Diethyl 2-Methylphenylphosphonate
1H-NMR (400 MHz, CDCl3):
.84 (m, 4H, CH2), 1.32 (t, JCH3-CH2 = 7.4 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
δ
7.44 (d, J = 8.0 Hz, 1H), 7.21 (d, J = 6.8 Hz, 1H), 7.09–7.02 (m, 2H)
135.6 (d, J = 4.4 Hz,
3
δ
C4), 132.2 (d, J = 8.0 Hz, C3, C6), 128.4 (d, J = 3.2 Hz, C5), 126.4 (d, J = 4.8 Hz, C2), 123.1 (d, J = 183.6 Hz,
+
C1), 65.8 (d, JCH2 = 6.8 Hz, 2C), 24.1 (d, JCH3 = 7.2 Hz, 2C), and 19.5. GC-MS m/z: [M + 1] ) calculated
for C H O P 228.0654; Found 229.0217.
11
18
3
3
.2.3. Compound 8c: Diethyl 4-Methoxyphenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.48 (d, J = 9.6 Hz, 2H), 7.22 (d, J = 10.0 Hz, 2H), 4.14 (m, 4H,
CH2), 3.59 (s, 3H), 1.68 (t, JCH3-CH2 = 6.4 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
165.2 (d, J = 4.6 Hz,
δ
δ
C4), 133.4 (d, J = 2.8 Hz, C2, C6), 128.2 (d, J = 174.6 Hz, C1), 125.2 (d, J = 6.4 Hz, C3, C5), 70.1 (d,
JCH2 = 6.2 Hz, 2C), and 53.2, 18.1 (d, JCH3 = 7.8 Hz, 2C).
3
.2.4. Compound 8d: Diethyl 4-Ethylphenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.31 (d, J = 7.8 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 3.62 (m, 4H, CH2),
.06 (m, 2H), 1.28 (t, JCH3-CH2 = 7.4 Hz, 6H), 1.22 (t, J = 6.8 Hz, 3H). 13C-NMR (100 MHz, CDCl3):
32.6 (d, J = 3.0 Hz, C4), 131.1 (d, J = 4.2 Hz, C2, C6), 127.1 (d, J = 4.0 Hz, C3, C5), 125.1 (d, J = 183.6 Hz,
C1), 62.1 (d, JCH2 = 7.2 Hz, 2C), 22.1 (d, JCH3 = 6.8 Hz, 2C), 19.5, and 15.1.
δ
2
δ
1
3
.2.5. Compound 8e: Diethyl 3-Nitrophenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.68 (s, 1H), 7.61 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 5.6 Hz, 1H), 7.32 (t,
J = 7.2 Hz, 1H), 3.78 (m, 4H, CH2), 1.29 (t, JCH3-CH2 = 8.0 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
162.4
d, J = 12.0 Hz, C5), 154.6 (d, J = 4.0 Hz, C4), 152.2 (d, J = 6.4 Hz, C6 ), 134.1 (d, J = 6.8 Hz, C2), 128.3 (d,
J = 6.8 Hz, C3), 123.1 (d, J = 179.6 Hz, C1), 70.3 (d, JCH2 = 9.2 Hz, 2C), and 23.1 (d, JCH3 = 7.2 Hz, 2C).
δ
δ
(
3
.2.6. Compound 8f: Diethyl 4-Fluorophenylphosphonate
1
H-NMR (400 MHz, CDCl ):
δ
7.72 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 7.6 Hz, 2H), 3.99 (m, 4H, CH2),
142.4 (d, J = 176.0 Hz, C4), 138.6 (d,
3
1
3
1
.48 (t, JCH3-CH2 = 8.4 Hz, 6H). C-NMR (100 MHz, CDCl3):
δ
J = 3.0 Hz, C2, C6), 132.9 (d, J = 6.0 Hz, C3, C5), 123.1 (d, J = 183.6 Hz, C1), 68.3 (d, JCH2 = 8.4 Hz
,
+
2
C), and 20.1 (d, JCH3 = 7.2 Hz, 2C). GC-MS m/z: [M + 1] ) calculated for C H FO P 232.0811;
10
15
3
Found 232.0656.
3
.2.7. Compound 8h: Diethyl 2,6-Difluorophenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.32 (d, J = 6.4 Hz, 1H), 7.11 (d, J = 6.4 Hz, 1H), 7.02 (t, J = 7.8 Hz
H), 4.06 (m, 4H, CH2), 1.62 (t, JCH3-CH2 = 4.4 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
δ
,
1
δ
176.6 (d,

Molecules 2020, 25, 290
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J = 4.4 Hz, C2, C6), 132.2 (d, J = 8.0 Hz, C3, C5), 126.1 (d, J = 174.2 Hz, C1), 125.6 (d, J = 6.0 Hz, C4),
6
1.8 (d, JCH2 = 5.4 Hz, 2C), and 22.6 (d, JCH3 = 6.8 Hz, 2C).
3
.2.8. Compound 9a: Dimethyl Phenylphosphonate
1H-NMR (400 MHz, CDCl3):
H), 3.84 (d, J = 11.0 Hz, 6H, CH3). C-NMR (100 MHz, CDCl3):
J = 10.2 Hz, C2, C6), 129.2 (d, J = 12.6 Hz, C3, C5), 125.4 (d, J = 182.8 Hz, C1), and 55.8 (d, J = 6.0 Hz,
δ 7.38 (d, J = 7.6 Hz, 2H), 7.31 (t, J = 7.0 Hz, 2H), 6.98 (t, J = 7.2 Hz,
13
1
δ 137.6 (d, J = 4.4 Hz, C4), 134.2 (d,
+
2
C). GC-MS m/z: [M] ) calculated for C H O P 186.0446, found 186.0432.
8 11 3
3
.2.9. Compound 9b: Dimethyl 4-Methoxyphosphonate
1H-NMR (400 MHz, CDCl3):
7.22 (d, J = 7.2 Hz, 2H), 7.16 (t, J = 7.2 Hz, 2H), 6.77 (t, J = 6.8 Hz,
H), 3.92 (d, J = 11.2 Hz, 6H, CH3), 3.45 (s, 3H). C-NMR (100 MHz, CDCl3):
δ
13
1
δ 132.2 (d, J = 4.0 Hz,
C4), 130.6 (d, J = 10.6 Hz, C2, C6), 127.4 (d, J = 11.8 Hz, C3, C5), 125.2 (d, J = 188.2 Hz, C1), 55.8 (d,
J = 6.0 Hz, 2C), and 52.4
3
.2.10. Compound 9c: Dimethyl 3-Nitrophenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.68 (s, 1H), 7.61 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 5.6 Hz, 1H), 7.32 (t,
J = 7.2 Hz, 1H), 3.62 (d, J = 11.2 Hz, 6H, CH3). 13C-NMR (100 MHz, CDCl3):
162.4 (d, J = 12.0 Hz,
C5), 154.6 (d, J = 4.0 Hz, C4), 152.2 (d, J = 6.4 Hz, C6 ), 134.1 (d, J = 6.8 Hz, C2), 128.3 (d, J = 6.8 Hz, C3),
23.1 (d, J = 179.6 Hz, C1), 70.3 (d, JCH2 = 9.2 Hz, 2C), and 23.1 (d, JCH3 = 7.2 Hz, 2C).
δ
δ
1
3
.2.11. Compound 10a: Diisopropyl Phenylphosphonate
1H-NMR (400 MHz, CDCl3):
7.58 (d, J = 7.8 Hz, 3H), 7.31 (t, J = 7.2 Hz, 2H), 4.69–4.51 (m, 2H),
.31 (d, J = 6.3 Hz, 6H), 1.12 (d, J = 6.3 Hz, 6H). C-NMR (100 MHz, CDCl ):
δ
13
1
1
δ
142.4 (d, J = 12.8 Hz, C5),
3
38.4 (d, J = 5.2 Hz, C2, C4), 135.6 (d, J = 6.8 Hz, C6 ), 128.3 (d, J = 6.8 Hz, C3), 123.1 (d, J = 181.6 Hz
,
C1), 69.8 (d, JCH2 = 9.2 Hz, 2C), and 24.2 (d, JCH3 = 7.2 Hz, 2C).
3
.2.12. Compound 10b: Diisopropyl 4-Methoxyphosphonate
1H-NMR (400 MHz, CDCl3):
7.51 (d, J = 7.4 Hz, 2H), 7.44 (d, J = 7.6 Hz, 2H), 4.48–4.36 (m, 2H),
.90 (s, 3H), 1.37 (d, J = 7.2 Hz, 6H), 1.21 (d, J = 7.8 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
156.4 (d,
δ
3
δ
J = 6.8 Hz, C4), 143.8 (d, J = 6.4 Hz, C3, C5 ), 132.3 (d, J = 6.8 Hz, C2, C6), 123.1 (d, J = 179.6 Hz, C1),
7
1.4 (d, JCH2 = 10.2 Hz, 2C), 52.8 (d, J = 8.2 Hz, OCH ), and 24.2 (d, JCH3 = 7.2 Hz, 2C).
3
3
.2.13. Compound 10c: Diisopropyl 3-Nitrophenylphosphonate
1H-NMR (400 MHz, CDCl3):
.22 (t, J = 7.0 Hz, 1H), 4.59–4.66 (m, 2H), 1.34 (d, J = 6.3 Hz, 6H), 1.19 (d, J = 6.3 Hz, 6H). 13C-NMR
161.3 (d, J = 11.0 Hz, C5), 158.6 (d, J = 4.4 Hz, C4), 151.0 (d, J = 6.8 Hz, C6), 132.4
d, J = 7.2 Hz, C2), 129.1 (d, J = 6.2 Hz, C3), 125.4 (d, J = 178.2 Hz, C1), 70.5 (d, JCH2 = 10.0 Hz, 2C), and
δ 7.39 (s, 1H), 7.61 (d, J = 7.4 Hz, 1H), 7.54 (d, J = 5.6 Hz, 1H),
7
(
(
100 MHz, CDCl3): δ
2
3.5 (d, JCH3 = 7.2 Hz, 2C).
3
.2.14. Compound 11a: Diphenyl Phenylphosphonate
1H-NMR (400 MHz, CDCl3):
C-NMR (100 MHz, CDCl3): 160.8 (d, J = 12.0 Hz), 156.4 (d, J = 4.4 Hz), 150.6 (d, J = 6.4 Hz), 142.6 (d,
δ 7.76 (m, 3H), 7.54 (m, 2H), 7.31–7.23 (m, 4H), 7.11–7.06 (m, 6H).
13
δ
J = 8.0 Hz), 141.6 (d, J = 6.6 Hz), 138.2 (d, J = 7.0 Hz), 135.7 (d, J = 8.4 Hz), 132.7 (d, J = 8.0 Hz), 128.3 (d,
J = 6.2 Hz,), and 123.1 (d, J = 189.6 Hz).
3
.2.15. Compound 11b: Diphenyl 4-Methoxyphosphonate
1H-NMR (400 MHz, CDCl3):
7.56 (dd, J = 13.2 Hz, J = 8.7 Hz, 2H), 7.21–7.19 (m, 5H), 7.17–7.08
m, 5H), 6.93 (m, 2H), 3.65 (s, 3H). 13C-NMR (100 MHz, CDCl3):
δ 159.4 (d, J = 12.2 Hz), 155.2 (d,
δ
1
2
(

Molecules 2020, 25, 290
9 of 12
J = 4.8 Hz), 150.4 (d, J = 7.4 Hz), 142.3 (d, J = 7.4 Hz), 138.6 (d, J = 8.4 Hz), 132.5 (d, J = 8.6 Hz),
29.4 (d, J = 7.4 Hz), 127.2 (d, J = 7.0 Hz), 124.6 (d, J = 174.6 Hz), 122.1 (d, J = 8.4 Hz), and 54.3 (d,
JCH2 = 10.4 Hz, OCH3).
1
3
.2.16. Compound 11c: Diphenyl 3-Nitrophenylphosphonate
1H-NMR (300 MHz, CDCl3)
7.83 (m, 4H), 7.21–7.19 (m, 4H), 7.17–7.08 (m, 3H), 6.93 (m, 3H).
C-NMR (100 MHz, CDCl3): 166.5 (d, J = 12.2 Hz), 156.8 (d, J = 4.8 Hz), 151.8 (d, J = 6.4 Hz), 132.1 (d,
δ
13
δ
J = 7.2 Hz), 130.4 (d, J = 7.0 Hz), 128.7 (d, J = 6.2 Hz), 127.9 (d, J = 6.8 Hz), 125.9 (d, J = 7.1 Hz), 123.9 (d,
J = 186.6 Hz), 122.6 (d, J = 7.4 Hz), and 119.6 (d, J = 7.2 Hz).
3
.2.17. Compound 12a: Dibenzyl Phenylphosphonate
H-NMR (400 MHz, CDCl3): 7.72 (m, 4H), 7.21–7.14 (m, 9H), 6.98 (dd, J1 = 9.2 Hz, J2 = 3.4 Hz,
H), 5.09–4.91 (m, 4H); 13C-NMR (100 MHz, CDCl3): 161.0 (d, J = 3.2 Hz), 155.6 (d, J = 4.6 Hz), 153.4
1
δ
2
δ
(
1
d, J = 4.2 Hz), 145.3 (d, J = 8.0 Hz), 137.4 (d, J = 8.0 Hz), 133.7 (d, J = 10.0 Hz), 128.5 (d, J = 8.4 Hz),
28.2 (d, J = 7.8 Hz), 127.9 (d, J = 6.4 Hz), 119.0 (d, J = 189.8 Hz), 114.1 (d, J1 = 14.0 Hz), and 67.4 (d,
J = 50.0 Hz).
3
.2.18. Compound 12b: Dibenzyl 4-Methoxyphosphonate
H-NMR (400 MHz, CDCl3): 7.65 (d, J = 12.4 Hz, 3H), 7.18–7.08 (m, 8H), 6.93 (dd, J1 = 9.4 Hz,
J2 = 4.0 Hz, 3H), 4.76–4.51 (m, 4H); 13C-NMR (100 MHz, CDCl3): 163.0 (d, J = 4.0), 154.6 (d, J = 7.2
1
δ
δ
Hz), 152.8 (d, J = 7.2 Hz), 147.6 (d, J = 7.2 Hz), 140.4 (d, J = 7.2 Hz), 138.2 (d, J = 7.6 Hz), 133.5 (d,
J = 8.0 Hz), 134.3 (d, J = 10.0 Hz), 130.2 (d, J = 6.2 Hz), 129.1 (d, J = 5.6 Hz), 124.9 (d, J = 8.0 Hz), 121.0
(d, J = 181.4 Hz), 113.1 (d, J = 12.8 Hz), and 59.4 (d, J = 22.0 Hz), 58.4.
3
.2.19. Compound 12c: Dibenzyl 3-Nitrophenylphosphonate
H-NMR (400 MHz, CDCl3): 7.55 (m, 3H), 7.20–7.17 (m, 7H), 7.03 (m, 2H), 6.78 (dd, J1 = 8.0
Hz, J2 = 4.2 Hz, 2H), 5.11–5.01 (m, 4H); 13C-NMR (100 MHz, CDCl3): 161.0 (d, J = 3.8 Hz), 152.6 (d,
1
δ
δ
J = 7.0 Hz), 151.0 (d, J = 7.8 Hz), 145.6 (d, J = 5.6 Hz), 142.2 (d, J = 8.0 Hz), 135.1 (d, J = 8.2 Hz), 132.1 (d,
J = 8.2 Hz), 130.1 (d, J = 6.8 Hz), 129.7 (d, J = 6.2 Hz), 123.4 (d, J = 6.8 Hz), 122.4 (d, J = 180.8 Hz), 112.1
(d, J = 11.0 Hz), and 58.4 (d, J = 7.6 Hz).
3
.2.20. Compound 12d: Dibenzyl 4-(Trifluoromethyl)phenylphosphonate
H-NMR (400 MHz, CDCl3): 7.48 (m, 3H), 7.16–7.07 (m, 8H), 6.73 (dd, J1 = 10.0 Hz, J2 = 5.2 Hz,
H), 4.98–4.75 (m, 4H); 13C-NMR (100 MHz, CDCl3): 168.2 (d, J = 5.2 Hz), 155.2 (d, J = 5.6 Hz), 153.3
1
δ
3
δ
(
(
d, J = 8.4 Hz), 149.7 (d, J = 6.0 Hz), 144.3 (d, J = 7.4 Hz), 139.0 (d, J = 8.6 Hz), 135.1 (d, J = 8.8 Hz), 132.4
d, J = 7.0 Hz), 129.4 (d, J = 5.8 Hz), 125.2 (d, J = 7.8 Hz), 123.4 (d, J = 183.5 Hz), 115.1 (d, J = 11.2 Hz),
and 59.4 (d, J = 7.8 Hz).
4
. Conclusions
In conclusion, we have reported the first cobalt-catalyzed cross-coupling of arylboronic acid
with alkyl/aryl phosphites under mild conditions in the presence of zinc powder. Moderate to
high yields of the products were observed in almost all the cases screened. This new protocol
is advantageous because it uses a non air-sensitive ligand, and is an inexpensive and non-toxic
cobalt-catalyst. The ligands involved are much simpler and less bulky than the ones that are employed
in Pd, Cu, or –Ni catalyzed reactions; hence, the proposed method provides a better alternative for
such transformations. The reaction also has a great substrate scope with arylboronic acid, as well
as with different dialkyl/diaryl phosphites, which broadens its scope and can make it a widely used
method. Further studies regarding the exact mechanistic pathway and future scope of this catalyst
system are still under way.

Molecules 2020, 25, 290
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Author Contributions: Methodology, I.H., J.M., T.H. and R.T.; Supervision, P.K.; Writing-review & editing, P.K.
All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Acknowledgments: We would like to thank Department of Chemistry, College of Science and Health, William
Paterson University (WPU) for providing the start-up funds. We would also like to thank WPU for providing
the necessary facilities to carry out this study. V.D. would like to thank Garden State–Louis Stokes Alliance for
Minority Participation (GS-LSAMP) for the financial support. P.K. would like to thank Center for Research (CfR)
Summer Award for financial support. P.K. would also like to thank Assigned Release Time (ART), WPU for
allowing for the time to carry out this research
Conflicts of Interest: The authors declare no competing financial interest.
References
1
.
Giannousis, P.P.; Bartlett, P.A. Phosphorus amino acid analogs as inhibitors of leucine aminopeptidase. J. Am.
Chem. Soc. 1987, 30, 1603. [CrossRef] [PubMed]
2
.
Maier, L.; Spörri, H. Organic Phosphorous Compounds 96. Resolution of 1-amino-2-(4-fluorophenyl)
ethylphosphonic acid as well as some di- and tri-peptides. Phosphorus Sulfur Silicon Relat. Elem. Tetrahedron Lett.
1
991, 61, 69. [CrossRef]
3
.
Sikorski, J.A.; Miller, M.J.; Braccolino, D.S.; Cleary, D.G.; Corey, S.; Font, J.L.; Gruys, K.J.; Han, C.Y.; Lin, K.;
Pansegrau, P.D.; et al. EPSP Synthase: The Design and Synthesis of Bisubstrate Inhibitors Incorporating
Novel 3-Phosphate Mimics. Phosphorus Sulfur Silicon Relat. Elem. 1993, 76, 115. [CrossRef]
4.
5.
6.
7.
8.
Meyer, J.H.; Bartlett, P.A. Macrocyclic Inhibitors of Penicillopepsin. 1. Design, Synthesis, and Evaluation of
an Inhibitor Bridged between P1 and P3. J. Am. Chem. Soc. 1998, 120, 4600. [CrossRef]
Stowasser, B.; Budt, K.; Jian-Qi, L.; Peyman, A.; Ruppert, D. New hybrid transition state analog inhibitors of
HIV protease with peripheric C -symmetry. Tetrahedron Lett. 1992, 33, 6625. [CrossRef]
2
Pratt, R. Inhibition of a class C beta-lactamase by a specific phosphonate monoester. Science 1989, 246, 917.
[
CrossRef]
Dhawan, B.; Redmor, D. Optically active 1-aminoalkylphosphonic acids. Phosphorous Sulfur Relat. Elem. 1987
2, 119. [CrossRef]
,
3
Duncan, K.; Walsh, C.T. ATP-dependent inactivation and slow binding inhibition of Salmonella typhimurium
D-alanine:D-alanine ligase (ADP) by (aminoalkyl)phosphinate and aminophosphonate analogues of
D-alanine. Biochemistry 1988, 27, 3709. [CrossRef]
9
.
Alonso, E.; Alonso, E.; Solis, A.; del Pozo, C. Synthesis of N-Alkyl-(
α-Aminoalkyl)Phosphine Oxides and
Phosphonic Esters as Potential HIV-Protease Inhibitors, Starting from α-Aminoacids. Synlett 2000, 5, 698.
1
0. Hirschmann, R.; Smith, A.; Taylor, C.; Benkovic, P.; Taylor, S.; Yager, K.; Sprengler, P.; Benkovic, S. Peptide
synthesis catalyzed by an antibody containing a binding site for variable amino acids. Science 1994, 265, 234.
[CrossRef]
1
1. Allen, J.; Atherton, F.; Hall, M.; Hassall, C.; Holmes, S.; Lambert, R.; Nisbet, L.; Ringrose, P. Phosphonopeptides,
a new class of synthetic antibacterial agents. Nature 1978, 272, 56–58. [CrossRef] [PubMed]
2. Atherton, F.R.; Hassall, C.H.; Lambert, R.W. Synthesis and structure-activity relationships of antibacterial
phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid.
J. Med. Chem. 1986, 29, 29. [CrossRef] [PubMed]
1
1
3. Sienczyc, M.; Oleksyszyn, J. Irreversible inhibition of serine proteases - design and in vivo activity of diaryl
alpha-aminophosphonate derivatives. Curr. Med. Chem. 2009, 16, 1673. [CrossRef] [PubMed]
4. Hu, Y.; Wan, Q.; Yang, S.; Song, B.; Bhadury, P.; Jin, L.; Yan, K.; Liu, F.; Chen, Z.; Xue, W. Synthesis and
1
Antiviral Activities of Amide Derivatives Containing the
008, 56, 998. [CrossRef] [PubMed]
α-Aminophosphonate Moiety. J. Agric. Food Chem.
2
1
1
1
5. Liu, C.; Szostak, M. Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The
Hirao Cross-Coupling of Amide Derivatives. Angew. Chem. Int. Ed. Engl. 2017, 56, 12718. [CrossRef]
6. Reddy, M.V.N.; Annar, S.; Krishna, A.B.; Reddy, G.C.S.; Reddy, C.S. Tetramethyl guanidine (TMG) catalyzed
synthesis of novel α-amino phosphonates by one-pot reaction. Org. Commun. 2010, 3, 39.
7. Rao, A.J.; Rao, P.V.; Rao, V.K.; Mohan, C.; Raju, C.N.; Reddy, C.S. Microwave Assisted One-pot Synthesis
of Novel
α-Aminophosphonates and Their Biological Activity. Bull. Korean Chem. Soc. 2010, 31, 1863.
[CrossRef]

Molecules 2020, 25, 290
11 of 12
1
8. Rezaei, Z.; Firouzabadi, H.; Iranpoor, N.; Ghaderi, A.; Jafari, M.; Jafari, A.; Zare, H. Design and one-pot
synthesis of -aminophosphonates and bis(alpha-aminophosphonates) by iron(III) chloride and cytotoxic
α
activity. Eur. J. Med. Chem. 2009, 44, 4266. [CrossRef]
1
9. Rao, X.; Song, Z.; He, L. Synthesis and antitumor activity of novel
dehydroabietylamine. Heteroatom Chem. 2008, 19, 512. [CrossRef]
α-aminophosphonates from diterpenic
2
0. Kraicheva, I.; Bogomilova, A.; Tsacheva, I.; Momekov, G.; Troev, K. Synthesis, NMR characterization and
in vitro antitumor evaluation of new aminophosphonic acid diesters. Eur. J. Med. Chem. 2009, 44, 3363.
[
CrossRef]
1. Xu, Y.; Yan, K.; Song, B.; Xu, G.; Yang, S.; Xue, W.; Hu, D.; Lu, P.; Ouyang, G.; Jin, L.; et al. Synthesis and
antiviral bioactivities of -aminophosphonates containing alkoxyethyl moieties. Molecules 2006, 11, 666.
CrossRef]
2
α
[
2
2
2. Du, S.; Faiger, H.; Belakhov, V.; Baasov, T. Towards the development of novel antibiotics: Synthesis and
evaluation of a mechanism-based inhibitor of Kdo8P synthase. Bioorg. Med. Chem. 1999, 7, 2671. [CrossRef]
3. Wu, H.C.; Yu, J.Q.; Spencer, J.B. Stereospecific Deoxygenation of Phosphine Oxides with Retention of
Configuration Using Triphenylphosphine or Triethyl Phosphite as an Oxygen Acceptor. Org. Lett. 2004, 25,
4
675. [CrossRef]
2
2
2
2
4. Al-Masum, M.; Livinghouse, T. Pd(0) Cu(I) cocatalyzed coupling of methylphenylphosphine-borane with
aryl halides and aryl nonaflates. Tetrahedron Lett. 1999, 40, 7731. [CrossRef]
5. Oshiki, T.; Imamoto, T. Unprecedented stereochemistry of the electrophilic arylation at chiral phosphorus.
J. Am. Chem. Soc. 1992, 114, 3975. [CrossRef]
6. Ley, S.; Thomas, A. Modern synthetic methods for copper-mediated C(aryl)[bond]O, C(aryl)[bond]N, and
C(aryl)[bond]S bond formation. Angew. Chem. Int. Ed. 2003, 42, 5400. [CrossRef]
7. Andaloussi, M.; Lindh, J.; Savmarker, J.; Sjoberg, P.; Larhed, M. Microwave-Promoted Palladium(II)-Catalyzed
C-P Bond Formation by Using Arylboronic Acids or Aryltrifluoroborates. Chem. Eur. J. 2009, 15, 13069.
[CrossRef]
2
2
3
3
3
8. Piontek, A.; Bisz, E.; Szostak, M. Iron-Catalyzed Cross-Couplings in the Synthesis of Pharmaceuticals:
In Pursuit of Sustainability. Angew. Chem. Int. Ed. 2018, 57, 11116. [CrossRef]
9. Kalek, M.; Ziadi, A.; Stawinski, J. Microwave-Assisted Palladium-Catalyzed Cross-Coupling of Aryl and
Vinyl Halides with H-Phosphonate Diesters. Org. Lett. 2008, 10, 4637. [CrossRef]
0. Zhuang, R.; Xu, J.; Cai, Z.; Tang, G.; Fang, M.; Zhao, Y. Copper-Catalyzed C-P Bond Construction via Direct
Coupling of Phenylboronic Acids with H-Phosphonate Diesters. Org. Lett. 2011, 13, 2110–2113. [CrossRef]
1. Hu, G.; Chen, W.; Fu, T.; Peng, Z.; Qiao, H.; Gao, Y.; Zhao, Y. Nickel-Catalyzed C-P Cross-Coupling of
Arylboronic Acids with P(O)H Compounds. Org. Lett. 2013, 15, 5362–5365. [CrossRef]
2. Ohmiya, H.; Wakabayashi, K.; Yorimitsu, H.; Oshima, K. Cobalt-catalyzed cross-coupling reactions of alkyl
halides with aryl Grignard reagents and their application to sequential radical cyclization/cross-coupling
reactions. Tetrahedron 2006, 62, 2207. [CrossRef]
3
3
3
3
3
3
3
3. Shinokubo, H.; Oshima, K. Transition Metal-Catalyzed Carbon Carbon Bond Formation with Grignard
−
Reagents—Novel Reactions with a Classic Reagent. Eur. J. Org. Chem. 2004, 10, 2081. [CrossRef]
4. Korn, T.J.; Schade, M.A.; Wirth, S.; Knochel, P. Cobalt(II)-Catalyzed Cross-Coupling between Polyfunctional
Arylcopper Reagents and Aryl Fluorides or Tosylates. Org. Lett. 2006, 8, 725. [CrossRef]
5. Amatore, M.; Gosmini, C.; Perichon, J. CoBr (Bpy): An Efficient Catalyst for the Direct Conjugate Addition
2
of Aryl Halides or Triflates onto Activated Olefins. J. Org. Chem. 2006, 71, 6130. [CrossRef]
6. Yorimitsu, H.; Oshima, K. New synthetic reactions catalyzed by cobalt complexes. Pure Appl. Chem. 2006
8, 441. [CrossRef]
,
7
7. Holzer, B.; Hoffman, R. Kumada–Corriu coupling of Grignard reagents, probed with a chiral Grignard
reagent. Chem. Commun. 2003, 6, 732–733. [CrossRef]
8. Datilus, V.; Abdulkarim, M.; Patrizio, A.; Kaur, P. Ter-pyridine catalyzed allylation of aldehydes and ketones
under metal-free condition. Tetrahedron Lett. 2016, 57, 2778. [CrossRef]
9. Cahiez, G.; Moyexic, A. Cobalt catalyzed cross-coupling reactions. Chem. Rev. 2010, 110, 1435. [CrossRef]

Molecules 2020, 25, 290
12 of 12
4
4
0. Xu, K.; Hu, H.; Yang, F.; Wu, Y. Synthesis of Aryl and Arylmethyl Phosphonates by Cross-Coupling of Aryl or
Arylmethyl Halides (X = I, Br and Cl) with Diisopropyl H-Phosphonate. Eur. J. Org. Chem. 2013, 2, 319–325.
CrossRef]
[
1. Wang, S.; Qiu, D.; Mo, F.; Zhang, Y.; Wang, J. Metal-Free Aromatic Carbon–Phosphorus Bond Formation via
a Sandmeyer-Type Reaction. J. Org. Chem. 2016, 81, 11603–11611. [CrossRef]
Sample Availability: Samples of the compounds 8a–8m, 9a–9c, 10a–10c, 11a–11c and 12a–12d are available from
the authors.
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2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access
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CC BY) license (http://creativecommons.org/licenses/by/4.0/).
(