Nickel-Catalyzed Phosphorylation of Phenol Derivatives via C-O/P-H Cross-Coupling

Article abstract of DOI:10.1021/acs.joc.6b00289

An efficient nickel-catalyzed phosphorylation of phenol derivatives with P(O)-H compounds via C-O/P-H cross-coupling is described. Under the reaction conditions, various phenyl pivalates coupled readily with hydrogen phosphoryl compounds to afford the corresponding coupling products aryl phosphonates and aryl phosphine oxides in good to high yields.

Full text of DOI:10.1021/acs.joc.6b00289

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Note
Nickel-Catalyzed Phosphorylation of Phenol
Derivatives via C-O/P-H Cross Coupling
Jia Yang, Jing Xiao, Tieqiao Chen, and Li-Biao Han
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00289 • Publication Date (Web): 07 Apr 2016
Downloaded from http://pubs.acs.org on April 11, 2016
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Nickel-Catalyzed Phosphorylation of Phenol Derivatives via C-O/P-H
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Cross Coupling
Jia Yang,†,a Jing Xiao,†,a Tieqiao Chen,*a and LiꢀBiao Han*b
aState Key Laboratory of Chemo/Biosensing and Chemo metrics, College of Chemistry and Chemical Engineering, Hunan
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University, Changsha 410082, China
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bNational Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305ꢀ8565, Japan
†
JY and JX contributed equally.
ABSTRACT
An efficient nickelꢀcatalyzed phosphorylation of phenol derivatives with P(O)ꢀH compounds via CꢀO/PꢀH cross
coupling is described. Under the reaction conditions, various phenyl pivalates coupled readily with hydrogen
phosphoryl compounds to afford the corresponding coupling products aryl phosphonates and aryl phosphine oxides in
good to high yields.
Aryl phosphonates and aryl phosphine oxides are important compounds in material chemistry, medicinal chemistry,
catalysis and organic synthesis.1 Traditionally, those compounds were synthesized by substitutions of P(O)Cl with
organolithium or Gringard reagents.2 The Michaelis−Arbusov reactions (reactions of alkyl halides with phosphites)
also were used to produce such compounds.3 Since the pioneering work reported by Hirao and coꢀworkers in 1980, the
transition metalꢀcatalyzed cross couplings of (pseudo)haloarenes with P(O)ꢀH compounds have been extensively
studied and emerged as one of the most efficient methods to access aryl phosphorus compounds.4 Those protocols all
depend on the transformation of organohalides.
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Scheme 1. Ni-catalyzed P-C bond formation via C-O activation.
Phenol derivatives are readily available and have attracted much attention as the green and efficient coupling
partners replacing the organohalides in the carbonꢀcarbon and carbonꢀheteroatom bonds coupling chemistry.5–8
Recently, we reported an efficient Niꢀcatalyzed carbonꢀphosphorus bondꢀforming reaction via CꢀO/PꢀH cross coupling
(Scheme 1).8 Various naphthyl pivalates coupled readily with hydrogen phosphoryl compounds to produce the
corresponding organophosphorus compounds in high yields.9 However, the phenol pivalates did not work under the
reaction conditions, which limited the application of this transformation.10 Herein, we reported that by tuning the
reaction conditions, the phosphorylation of phenol pivalates with hydrogen phosphoryl compounds was also achieved.
Various aryl phosphonates and aryl phosphine oxides were produced in good to high yields by using this
nickelꢀcatalyzed CꢀO/PꢀH cross coupling (Scheme 1).9
Table 1. Conditions optimization of Ni-catalyzed C-O/P-H cross coupling of phenyl pivalates 1a with diisopropoyl
phosphonate 2a.a
O
O
cat. Ni
i-PrO P H
i-PrO
OPiv
P OPr-i
OPr-i
+
1a
2a
3a
entry ligand
base
solvent
temp. Yieldb
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3
4
5
dcype
dcype
dcype
dcype
dcype
Na2CO3
K2CO3
K3PO4
Cs2CO3
EtONa
dioxane 100 oC
dioxane 100 oC
dioxane 100 oC
dioxane 100 oC
dioxane 100 oC
n.d.
18%
23%
41%
n.d.
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dcype
dcype
dcype
dcype
dcype
dcype
dcype
dcype
dcype
dcype
PCy3
tꢀBuOLi
tꢀBuONa
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
dioxane 100 oC
dioxane 100 oC
7%
9%
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2
3
4
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6
7
8
8
toluene
hexane
100 oC
100 oC
69%
20%
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19c
20d
CH3CN 100 oC trace
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DMF
100 oC
80 oC
n.d.
n.d.
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
90 oC
28%
29%
18%
n.d.
110 oC
120 oC
100 oC
100 oC
100 oC
100 oC
100 oC
dppp
n.d.
dppf
n.d.
dcype
dcype
94%
25%
aReaction conditions: 1a (0.2 mmol), (iꢀPrO)2P(O)H (0.3mmol), 10mol% Ni(COD)2, base (0.22mmol), solvent (1
mL), 24 h. bGC yield using tridecane as an internal standard. c(iꢀPrO)2P(O)H was added in two portions (0.15 mmol 2a
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was added after the reaction mixture was stirred for 12 hours). dPhenyl dimethyl carbamate was used as a substrate.
We initiated the work with examining the reactivity of phenyl pivalate 1a with diisopropyl phosphonate 2a by using
the previous Ni(COD)2/dcype (1,2ꢀbis(dicyclohexylphosphino)ethane) catalyst and the obtained results were compiled
in Table 1. A screening on the additive showed that a suitable base was essential for the reaction (entries 1–7). At first,
the yield increased as the basicity with Cs2CO3 giving the highest yield of the product (entries 1–4). However, the
addition of stronger bases like EtONa, tꢀBuOLi and tꢀBuONa lead to dramatic decrease of the reaction efficiency
which perhaps was due to the hydrolysis of phosphoryl groups under the reaction conditions (entries 5–7). Thus, in the
presence of Ni(COD)2 (10 mol%), dcype (10 mol%) and Cs2CO3 (1.1 equiv), phenyl pivalate 1a reacted with 2a in
dioxane at 100 oC to produce the corresponding coupling product 3a in 41% yield (entry 4). The yield of 3a was further
increased to 69% by using toluene as the solvent (entry 8).11 Low yield was afforded when the reaction was performed
in the apolar hexane, and no product was detected in the polar MeCN and DMF (entries 9–11). Either lowering or
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elevating the reaction temperature led to decrease of the reaction efficiency (entries 12ꢀ15).12 The phosphine ligands
were also crucial for the transformation. No reaction took place with other selected ligands like PCy3, dppp
(1,3ꢀbis(diphenylphosphino)propane) and dppf (1,1'ꢀbis(diphenylphosphino)ferrocene) under similar reaction
conditions (entries 16–18). Worth noting is that when 2a was added in two portions (0.75 equiv was added at the start
and the other part was added after 12 h), an excellent yield (94% yield) of product 3a was obtained (entry 19).13,14
Carbamate could also be converted to the corresponding product 3a in 25% yield under the reaction conditions (entry
20).
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This transformation is applicable to other substrates. As shown in Table 2, both electronꢀrich and electronꢀdeficient
phenyl pivalates reacted with a variety of hydrogen phosphoryl compounds under the present reaction conditions,
producing the corresponding coupling products in good to high yields. Thus, 4ꢀmethylphenyl pivalate was found as
reactive as phenyl pivalate 1a to react with diisopropyl phosphonate 2a, giving the expected product 3b in 93% yield
(entries 1 and 2). 3ꢀMethylphenyl pivalate also coupled with 2a readily (entry 3). However, when 2ꢀmethylphenyl
pivalate was employed as a substrate, a relatively low yield was given (entry 4). This perhaps was due to the highly
steric hindrance of the substrate. Other selected derivatives of pivalates with electronꢀdonating groups like butyl,
methoxy and amide group on the benzene ring all served as good substrates and were converted to the corresponding
aryl phosphonates in good to high yields (entries 5–7). 4ꢀFluorophenyl pivalate was phosphorylated successfully by
diisopropyl phosphonate in the present coupling system with fluoro group intact (entry 8), whereas a chloro group did
not survive. When 4ꢀchlorophenyl pivalate was loaded, a diphosphorylated product 3i was produced under similar
reaction conditions (entry 9). Substrates with strong electronꢀwithdrawing group like CN, CF3 and Ac group on the
benzene ring also coupled with diisopropyl phosphonate smoothly, furnishing the desired ary phosphonates in high
yields (entries 10–12). Phenyl pivalates bearing phenyl group at ortho or para position also reacted with 2a to yield the
expected products 3m and 3n in 52% and 94% yields, respectively (entries 13 and 14). To our delight, two phosphoryl
groups were introduced into the molecule via a oneꢀpot process by a diphosphorylation of bispivalates as exemplified
by 1,4ꢀphenylene bispivalates (entry 15). Intriguingly, the heteroaryl phosphonate 3p was also obtained in 71% yield
from the nickelꢀcatalyzed reaction of 3ꢀpyrindinyl pivalate with diisopropyl phosphonate via CꢀO/PꢀH cross coupling
(entry 16).
Table 2. Ni-catalyzed C-O/P-H cross coupling of phenyl pivalates 1 with P(O)-H compounds producing aryl phosphonates
and aryl phosphine oxides 3.a
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aReaction conditions: 0.2 mmol 1, 0.3mmol 2 (added in two portions: 0.15 mmol 2a was added after the reaction
mixture was stirred for 12 hours), 10 mol% Ni(COD)2, 10 mol% dcype, 0.22 mmol Cs2CO3, 1 mL toluene, 100 oC, 24
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b
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h. 20% mol Ni(COD)2, 20 mol% dcype. 110oC, 46 h. 0.6 mmol 2a was added. 100oC, 46 h. 110 C. Oneꢀpot
reaction, 0.2 mmol 2.
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As to the hydrogen phosphoryl compounds, comparing with Hꢀphosphonate 2a, secondary phosphine oxides also
served well and showed higher reactivity in the current catalytic system.15 Thus, nꢀBu2P(O)H 2b reacted readily with
an equivalent phenyl pivalate 1a to produce the corresponding phenyl dibutyl phosphine oxide 3p in 95% yield (entry
17). tꢀBuPhP(O)H 2c also coupled with 1a under similar reaction conditions, leading to the production of aryl
phosphine oxide 3r in 93% yield (entry 18). Even the bulky dicyclohexyl phosphine oxide 2d was also found reactive
to react with both electronꢀrich and electronꢀdeficient phenyl pivalates, generating the corresponding aryl phosphine
oxides in high yields (entries 20–23).
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We deduce that this Niꢀcatalyzed cross coupling takes place via a catalytic cycle as shown in Scheme 2.16 The
oxidative addition of Ni(COD)2 with phenyl pivalates 1 at an elevated temperature took place to generate the
intermediate B,16a,16b followed by ligand exchange to give the intermediate C16e,16f in the presence of a stronger base
Cs2CO3. The intermediate C underwent reductive elimination to give the corresponding coupling product 3.
Scheme 2. Plausible mechanism for the Ni-catalyzed C-O/P-H cross coupling of phenyl pivalates with P(O)-H compounds.
In summary, an efficient Niꢀcatalyzed phosphorylation of phenyl pivalates with hydrogen phosphoryl compounds
was developed. This Niꢀcatalyzed CꢀO/PꢀH cross coupling has a broad general applicability in PꢀC bond formation.
Various aryl phosphorus compounds were prepared successfully by using the easily available phenol derivatives as the
arylating reagents via CꢀO activation.
EXPERIMENTAL SECTION
General information: All reactions were carried out in ovenꢀdried Schlenk tubes under N2 atmosphere. Solvents were
distilled after treatment by calcium hydride. Reagents were used as received unless otherwise noted. Column
chromatography was performed using Silica Gel 60 (particle size 37–54 ꢁm). The pure products were obtained by
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means of column chromatography (petroleum ether and ethyl acetate were used as the gradient eluting
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solvents). H NMR, 13C NMR and 31P NMR data were acquired on a 400 spectrometer (400 MHz for H, 100 MHz
for 13C, and 162 MHz for 31P NMR spectroscopy). Chemical shifts for 1H NMR are referred to internal Me4Si (0 ppm)
and reported as follows: chemical shift (δ ppm), multiplicity, coupling constant (Hz) and integration. Data for 31P NMR
were relative to H3PO4 (85% solution in D2O, 0 ppm). The ionization method of the highꢀresolution mass spectrum
(HRMS) is Electron Impact (EI). The type of the mass analyzer is quadrupole. IR data were recorded as KBr pellets on
a FTIR spectrophotometer and are reported as wavenumbers (cm–1).
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Synthesis of starting materials: Aryl pivalates have been prepared via the classical reaction of the free phenol in the
presence of Et3N (1.20 equiv), PivCl (1.20 equiv) in DCM at room temperature. The products were purified by regular
flash chromatography (petroleum ether / EtOAc mixtures).7a
Typical procedure for the Nickel-catalyzed C–O/P–H cross coupling of P(O)–H compounds with alcohol
derivatives: Under N2 atmosphere, 0.2 mmol phenyl pivalate 1a, 10 mol% Ni(COD)2, 10 mol% dcype, 1.1 equiv
Cs2CO3 and 1 mL toluene were charged into a 10 mL schlenck tube, then 0.15 mmol (iꢀPrO)2P(O)H 2a was added to
the mixture. After the reaction was processed in 100 oC for 12 hours, the other 0.15 mmol (iꢀPrO)2P(O)H 2a was added
o
to the glass tube under N2 atmosphere. The mixture was further stirred at 100 C for 12 hours. After removal of the
volatile, the residues were passed through a short silica chromatography (particle size 37–54 ꢁm, petroleum ether /ethyl
acetate as eluent) to afford analytically pure organophosphorus compounds 3.
Diisopropyl phenylphosphonate (3a). Purification by chromatography (petroleum ether/EtOAc = 2:1) afforded 3a
(43.6 mg, 90%) as a colorless oil. Rf = 0.59 (petroleum ether/EtOAc = 1:1); 1H NMR (400 MHz CDCl3): δ 7.85–7.79
(m, 2H), 7.54–7.42 (m, 3H), 4.75–4.64 (m, 2H), 1.37 (d, J = 6.4 Hz, 6H), 1.23 (d, J = 6.0 Hz, 6H). 13C NMR (100 MHz
CDCl3): δ 132.0 (d, JCꢀP = 3.0 Hz), 131.6 (d, JCꢀP = 9.7 Hz), 129.9 (d, JCꢀP = 187.4 Hz), 128.2 (d, JCꢀP = 14.9 Hz), 70.6
(d, JCꢀP = 5.5 Hz), 24.0 (d, JCꢀP = 3.9 Hz), 23.8 (d, JCꢀP = 4.8 Hz). 31P NMR (162 MHz CDCl3): δ 16.52. This compound
is known. 17
Diisopropyl p-tolylphosphonate (3b). Purification by chromatography (petroleum ether/EtOAc = 3:1) afforded 3b
(47.6 mg, 93%) as a colorless oil. Rf = 0.49 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ 7.73–7.68
(m, 2H), 7.28–7.24 (m, 2H), 4.72–4.61 (m, 2H), 2.39 (s, 3H), 1.36 (d, J = 6.0 Hz, 6H), 1.22 (d, J = 6.0 Hz, 6H). 13C
NMR (100 MHz CDCl3): δ 142.6 (d, JCꢀP = 3.1 Hz), 131.8 (d, JCꢀP = 10.2 Hz), 129.1 (d, JCꢀP = 15.3 Hz), 126.6 (d, JCꢀP
= 189.7 Hz), 70.6 (d, JCꢀP = 5.4 Hz), 24.1 (d, JCꢀP = 3.9 Hz), 23.8 (d, JCꢀP = 4.8 Hz), 21.6 (d, JCꢀP = 1.1 Hz). 31P NMR
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(162 MHz CDCl3): δ 17.38. This compound is known. 17
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Diisopropyl m-tolylphosphonate (3c). Purification by chromatography (petroleum ether/EtOAc = 2:1) afforded 3c
(38.4 mg, 75%) as a colorless oil. Rf = 0.40 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ 7.66–7.57
(m, 2H), 7.36–7.28 (m, 2H), 4.71–4.66 (m, 2H), 2.39 (s, 3H), 1.37 (d, J = 6.0 Hz, 6H), 1.23 (d, J = 6.4 Hz, 6H). 13C
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NMR (100 MHz CDCl3): δ 138.1 (d, JCꢀP = 14.8 Hz), 132.9 (d, JCꢀP = 3.1 Hz), 132.3 (d, JCꢀP = 9.9 Hz), 129.7 (d, JCꢀP
=
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186.8 Hz), 128.7 (d, JCꢀP = 9.5 Hz), 128.2 (d, JCꢀP = 15.7 Hz), 70.7 (d, JCꢀP = 5.5 Hz), 24.1 (d, JCꢀP = 3.9 Hz), 23.8 (d,
JCꢀP = 4.8 Hz), 21.3. 31P NMR (162 MHz CDCl3): δ 17.17. This compound is known. 17
Diisopropyl o-tolylphosphonate (3d). Purification by chromatography (petroleum ether/EtOAc = 3:1) afforded 3d
(18.4 mg, 36%) as a colorless oil. Rf = 0.51 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ 7.97–7.92
(m, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.28–7.22 (m, 2H), 4.77–4.65 (m, 2H), 2.58 (s, 3H), 1.38 (d, J = 6.4 Hz, 6H), 1.24 (d,
J = 6.4 Hz, 6H). 13C NMR (100 MHz CDCl3): δ 141.6 (d, JCꢀP = 9.7 Hz), 133.8 (d, JCꢀP = 10.4 Hz), 132.2 (d, JCꢀP = 2.9
Hz), 131.1 (d, JCꢀP = 14.7 Hz), 128.3 (d, JCꢀP = 183.8 Hz), 125.3 (d, JCꢀP = 14.9 Hz), 70.6 (d, JCꢀP = 5.7 Hz), 24.1 (d, JCꢀP
= 4.1 Hz), 23.8 (d, JCꢀP = 4.6 Hz), 21.3 (d, JCꢀP = 3.4 Hz). 31P NMR (162 MHz CDCl3): δ 17.19. This compound is
known. 17
Diisopropyl (4-butylphenyl)phosphonate (3e). Purification by chromatography (petroleum ether/EtOAc = 3:1)
afforded 3e (41.7 mg, 70%) as a colorless oil. Rf = 0.54 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ
7.74–7.69 (m, 2H), 7.29–7.24 (m, 2H), 4.71–4.63 (m, 2H), 2.65 (t, J = 8.0 Hz, 2H), 1.65–1.57 (m, 2H), 1.40–1.31 (m,
8H), 1.22 (d, J = 6.4 Hz, 6H), 0.93 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz CDCl3): δ 147.5 (d, JCꢀP = 3.1 Hz), 131.8
(d, JCꢀP = 10.3 Hz), 128.4 (d, JCꢀP = 15.3 Hz), 126.7 (d, JCꢀP = 189.8 Hz), 70.6 (d, JCꢀP = 5.4 Hz), 35.7 (d, JCꢀP = 0.8 Hz),
33.2, 24.1 (d, JCꢀP = 4.0 Hz), 23.8 (d, JCꢀP = 4.8 Hz), 22.3, 13.9. 31P NMR (162 MHz CDCl3): δ 17.44. This compound
is known. 17
Diisopropyl (4-methoxyphenyl)phosphonate (3f). Purification by chromatography (petroleum ether/EtOAc = 2:1)
afforded 3f (50.0 mg, 92%) as a colorless oil. Rf = 0.32 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ
7.77–7.72 (m, 2H), 6.96–6.94 (m, 2H), 4.71–4.59 (m, 2H), 3.85 (s, 3H), 1.36 (d, J = 6.0 Hz, 6H), 1.22 (d, J = 6.4 Hz,
6H). 13C NMR (100 MHz CDCl3): δ 162.6 (d, JCꢀP = 3.3 Hz), 133.7 (d, JCꢀP = 11.2 Hz), 121.2 (d, JCꢀP = 194.2 Hz),
113.8 (d, JCꢀP = 15.9 Hz), 70.4 (d, JCꢀP = 5.4 Hz), 55.3, 24.1 (d, JCꢀP = 3.9 Hz), 23.8 (d, JCꢀP = 4.8 Hz). 31P NMR (162
MHz CDCl3): δ 17.49. This compound is known. 17
Diisopropyl (4-pivalamidophenyl)phosphonate (3g). Purification by chromatography (petroleum ether/EtOAc =
1
1:1) afforded 3g (55.9 mg, 82%) as a white solid. Rf = 0.27 (petroleum ether/EtOAc = 1:1); H NMR (400 MHz
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CDCl3): δ 7.72–7.67 (m, 2H), 7.60–7.57 (m, 2H), 7.48 (s, 1H), 4.62–4.54 (m, 2H), 1.29 (d, J = 6.0 Hz, 6H), 1.26 (s,
9H), 1.14 (d, J = 6.4 Hz, 6H). 13C NMR (100 MHz CDCl3): δ 175.9, 140.6 (d, JCꢀP = 3.4 Hz), 131.9 (d, JCꢀP = 10.6 Hz),
123.8 (d, JCꢀP = 192.0 Hz), 118.1 (d, JCꢀP = 15.2 Hz), 69.7 (d, JCꢀP = 5.4 Hz), 38.8, 26.5, 23.1 (d, JCꢀP = 4.0 Hz), 22.8 (d,
JCꢀP = 4.8 Hz). 31P NMR (162 MHz CDCl3): δ 16.45. This compound is known. 18
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Diisopropyl (4-fluorophenyl)phosphonate (3h). Purification by chromatography (petroleum ether/EtOAc = 3:1)
afforded 3h (43.2 mg, 83%) as a colorless oil. Rf = 0.40 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ
7.86–7.79 (m, 2H), 7.14 (ddd, J = 2.8 Hz, J = 8.8 Hz, J = 8.8 Hz, 2H), 4.73–4.65 (m, 2H), 1.37 (d, J = 6.4 Hz, 6H),
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1.27 (d, J = 6.0 Hz, 6H). 13C NMR (100 MHz CDCl3): δ 165.2 (dd, JCꢀF = 251.4 Hz, JCꢀP = 3.8 Hz), 134.2 (dd, JCꢀF
=
10.0 Hz, JCꢀP = 2.4 Hz), 126.1 (dd, JCꢀF = 3.5 Hz, JCꢀP = 192.2 Hz), 115.6 (dd, JCꢀF = 18.7 Hz, JCꢀP = 5.1 Hz), 70.9 (d,
JCꢀP = 5.5 Hz), 24.0 (d, JCꢀP = 4.0 Hz), 23.8 (d, JCꢀP = 4.7 Hz). 31P NMR (162 MHz CDCl3): δ 15.59. This compound is
known. 9b
Tetraisopropyl 1,4-phenylenebis(phosphonate) (3i). Purification by chromatography (petroleum ether/EtOAc =
1:1) afforded 3i (pivalate 1i, 66.6 mg, 82%; pivalate 1o, 41.5 mg, 51%) as a white solid. Rf = 0.58 (EtOAc); m.p.: 97–
98 oC; 1H NMR (400 MHz CDCl3): δ 7.91–7.87 (m, 4H), 4.78–4.67 (m, 4H), 1.38 (d, J = 6.0 Hz, 12H), 1.24 (d, J = 6.4
Hz, 12H). 13C NMR (100 MHz CDCl3): δ 134.1 (dd, JCꢀP = 3.0 Hz, JCꢀP = 186.5 Hz), 131.4 (dd, JCꢀP = 12.2 Hz, JCꢀP
=
3.7 Hz), 71.2 (d, JCꢀP = 5.7 Hz), 24.0 (d, JCꢀP = 3.8 Hz), 23.8 (d, JCꢀP = 4.6 Hz).31P NMR (162 MHz CDCl3): δ 14.79.
HRMS: Cal. for C18H32O6P2 406.1674. Found 406.1660. IR: 2983, 2935, 1469, 1249, 1143, 979 cmꢀ1.
Diisopropyl (4-cyanophenyl)phosphonate (3j). Purification by chromatography (petroleum ether/EtOAc = 2:1)
afforded 3j (43.8 mg, 82%) as a colorless oil. Rf = 0.33 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ
7.95–7.89 (m, 2H), 7.76–7.73 (m, 2H), 4.78–4.70 (m, 2H), 1.39 (d, J = 6.4 Hz, 6H), 1.24 (d, J = 6.0 Hz, 6H). 13C NMR
(100 MHz CDCl3): δ 135.5 (d, JCꢀP = 187.3 Hz), 132.2 (d, JCꢀP = 9.7 Hz), 131.9 (d, JCꢀP = 14.8 Hz), 117.9 (d, JCꢀP = 1.4
Hz), 115.7 (d, JCꢀP = 3.6 Hz), 71.6 (d, JCꢀP = 5.8 Hz), 24.0 (d, JCꢀP = 4.1 Hz), 23.8 (d, JCꢀP = 4.7 Hz). 31P NMR (162
MHz CDCl3): δ 13.12. This compound is known. 18
Diisopropyl (4-(trifluoromethyl)phenyl)phosphonate (3k). Purification by chromatography (petroleum
ether/EtOAc = 3:1) afforded 3k (57.7 mg, 93%) as a colorless oil. Rf = 0.51 (petroleum ether/EtOAc = 2:1); 1H NMR
(400 MHz CDCl3): δ 7.98–7.93 (m, 2H), 7.73–7.71 (m, 2H), 4.79–4.68 (m, 2H), 1.39 (d, J = 6.0 Hz, 6H), 1.24 (d, J =
6.4 Hz, 6H). 13C NMR (100 MHz CDCl3): δ 134.4 (d, JCꢀP = 187.9 Hz), 133.7 (dd, JCꢀP = 3.3 Hz, JCꢀF = 32.3 Hz), 132.1
(d, JCꢀP = 10.0 Hz), 125.2 (dq, JCꢀP = 3.7 Hz, JCꢀF = 15.0 Hz), 123.6 (q, JCꢀF = 271.2 Hz), 71.3 (d, JCꢀP = 5.7 Hz), 24.0 (d,
JCꢀP = 4.0 Hz), 23.8 (d, JCꢀP = 4.7 Hz). 31P NMR (162 MHz CDCl3): δ 14.07. This compound is known. 18
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Diisopropyl (4-acetylphenyl)phosphonate (3l). Purification by chromatography (petroleum ether/EtOAc = 3:1)
afforded 3l (45.0 mg, 79%) as a colorless oil. Rf = 0.44 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ
8.04–8.01 (m, 2H), 7.95–7.90 (m, 2H), 4.77–4.69 (m, 2H), 2.65 (s, 3H), 1.39 (d, J = 6.0 Hz, 6H), 1.24 (d, J = 6.4 Hz,
6H). 13C NMR (100 MHz CDCl3): δ 197.6, 139.6 (d, JCꢀP = 3.1 Hz), 134.9 (d, JCꢀP = 186.1 Hz), 132.0 (d, JCꢀP = 9.9 Hz),
127.9 (d, JCꢀP = 15.0 Hz), 71.2 (d, JCꢀP = 5.6 Hz), 26.8, 24.0 (d, JCꢀP = 4.0 Hz), 23.8 (d, JCꢀP = 4.7 Hz). 31P NMR (162
MHz CDCl3): δ 14.60. This compound is known. 19
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Diisopropyl [1,1'-biphenyl]-2-ylphosphonate (3m). Purification by chromatography (petroleum ether/EtOAc = 3:1)
afforded 3m (33.2 mg, 52%) as a colorless oil. Rf = 0.49 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3):
δ 8.11–8.05 (m, 1H), 7.53 (t, J = 7.2 Hz, 1H), 7.46–7.29 (m, 7H), 4.63–4.52 (m, 2H), 1.16 (d, J = 6.4 Hz, 6H), 1.12 (d,
J = 6.4 Hz, 6H). 13C NMR (100 MHz CDCl3): δ 145.9 (d, JCꢀP = 9.4 Hz), 141.7 (d, JCꢀP = 3.9 Hz), 133.6 (d, JCꢀP = 10.0
Hz), 131.7 (d, JCꢀP = 2.9 Hz), 131.5 (d, JCꢀP = 14.1 Hz), 129.7, 128.5 (d, JCꢀP = 187.8 Hz), 127.3, 127.2 (d, JCꢀP = 9.0
Hz), 126.7 (d, JCꢀP = 14.6 Hz), 70.7 (d, JCꢀP = 6.3 Hz), 23.9 (d, JCꢀP = 4.2 Hz), 23.7 (d, JCꢀP = 4.9 Hz). 31P NMR (162
MHz CDCl3): δ 16.16. This compound is known. 20
Diisopropyl [1,1'-biphenyl]-4-ylphosphonate (3n). Purification by chromatography (petroleum ether/EtOAc = 3:1)
afforded 3n (59.8 mg, 94%) as a colorless oil. Rf = 0.44 (petroleum ether/EtOAc = 2:1); 1H NMR (400 MHz CDCl3): δ
7.91–7.86 (m, 2H), 7.69–7.66 (m, 2H), 7.61 (d, J = 7.6 Hz, 2H), 7.46 (t, J = 8.0 Hz, 2H), 7.39 (t, J = 7.2 Hz, 2H), 4.76–
4.68 (m, 2H), 1.39 (d, J = 6.4 Hz, 6H), 1.26 (d, J = 6.0 Hz, 6H). 13C NMR (100 MHz CDCl3): δ 144.8 (d, JCꢀP = 3.2 Hz),
140.1 (d, JCꢀP = 0.7 Hz), 132.3 (d, JCꢀP = 10.2 Hz), 128.9, 128.5 (d, JCꢀP = 189.3 Hz), 128.1, 127.3, 127.0 (d, JCꢀP = 15.1
Hz), 70.8 (d, JCꢀP = 5.5 Hz), 24.1 (d, JCꢀP = 3.9 Hz), 23.9 (d, JCꢀP = 4.8 Hz). 31P NMR (162 MHz CDCl3): δ 16.84. This
compound is known. 9b
Diisopropyl pyridin-3-ylphosphonate (3o). Purification by chromatography (petroleum ether/EtOAc = 1:1)
afforded 3o (34.5 mg, 71%) as a colorless oil. Rf = 0.28 (petroleum ether/EtOAc = 1:1); 1H NMR (400 MHz CDCl3): δ
8.91–8.90 (m, 1H), 8.68–8.67 (m, 1H), 8.05–8.00 (m, 1H), 7.32–7.31 (m, 1H), 4.70–4.65 (m, 2H), 1.33–1.30 (m, 6H),
1.19–1.17 (m, 6H). 13C NMR (100 MHz CDCl3): δ 152.6 (br), 152.2 (d, JCꢀP = 12.1 Hz), 139.3 (d, JCꢀP = 8.2 Hz), 126.4
(d, JCꢀP = 188.8 Hz), 123.2 (d, JCꢀP = 11.4 Hz), 71.4 (d, JCꢀP = 5.8 Hz), 24.0 (d, JCꢀP = 4.1 Hz), 23.8 (d, JCꢀP = 4.8 Hz).
31P NMR (162 MHz CDCl3): δ 13.49. This compound is known. 18
Dibutyl(phenyl)phosphine oxide (3p). Purification by chromatography (petroleum ether/EtOAc = 1:2) afforded 3p
(45.2 mg, 95%) as a white solid. Rf = 0.53 (EtOAc); 1H NMR (400 MHz CDCl3): δ 7.73–7.68 (m, 2H), 7.53–7.49 (m,
3H), 2.04–1.81 (m, 4H), 1.67–1.54 (m, 2H), 1.48–1.31 (m, 6H), 0.87 (t, J = 7.2 Hz, 6H). 13C NMR (100 MHz CDCl3):
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δ 132.7 (d, JCꢀP = 91.6 Hz), 131.4 (d, JCꢀP = 2.7 Hz), 130.4 (d, JCꢀP = 8.6 Hz), 128.6 (d, JCꢀP = 11.0 Hz), 29.7 (d, JCꢀP
=
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68.1 Hz), 24.1 (d, JCꢀP = 14.4 Hz), 23.5 (d, JCꢀP = 4.1 Hz), 13.6. 31P NMR (162 MHz CDCl3): δ 41.91. This compound
is known. 21
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Tert-butyldiphenylphosphine oxide (3q). Purification by chromatography (petroleum ether/EtOAc = 1:2) afforded
3q (48.0 mg, 93%) as a white solid. Rf = 0.60 (EtOAc); 1H NMR (400 MHz CDCl3): δ 7.96 (dd, J = 8.8 Hz, J = 8.8 Hz,
4H), 7.54–7.46 (m, 6H), 1.25 (d, J = 14.8 Hz, 9H). 13C NMR (100 MHz CDCl3): δ 132.2 (d, JCꢀP = 8.0 Hz), 131.5 (d,
JCꢀP = 2.5 Hz), 131.1 (d, JCꢀP = 89.8 Hz), 128.3 (d, JCꢀP = 10.8 Hz), 34.0 (d, JCꢀP = 70.4 Hz), 25.2. 31P NMR (162 MHz
CDCl3): δ 39.22. This compound is known. 21
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Dicyclohexyl(phenyl)phosphine oxide (3r). Purification by chromatography (petroleum ether/EtOAc = 1:2)
afforded 3r (56.4 mg, 97%) as a white solid. Rf = 0.43 (EtOAc); 1H NMR (400 MHz CDCl3): δ 7.67 (dd, J = 8.4 Hz, J
= 8.4 Hz, 2H), 7.54–7.42 (m, 3H), 2.06 (br, 4H), 1.82–1.61 (m, 8H), 1.32–1.12 (m, 10H). 13C NMR (100 MHz CDCl3):
δ 131.5 (d, JCꢀP = 7.6 Hz), 131.2 (d, JCꢀP = 2.3 Hz), 129.8 (d, JCꢀP = 85.2 Hz), 128.2 (d, JCꢀP = 10.3 Hz), 35.7 (d, JCꢀP
=
67.1 Hz), 26.4 (d, JCꢀP = 12.4 Hz), 26.3 (d, JCꢀP = 11.1 Hz), 25.8, 25.5 (d, JCꢀP = 1.8 Hz), 24.6 (d, JCꢀP = 3.1 Hz). 31P
NMR (162 MHz CDCl3): δ 45.74. This compound is known. 22
Dicyclohexyl(p-tolyl)phosphine oxide (3s). Purification by chromatography (petroleum ether/EtOAc = 1:2)
afforded 3s (58.4 mg, 96%) as a colorless oil. Rf = 0.47 (EtOAc); 1H NMR (400 MHz CDCl3): δ 7.55 (dd, J = 8.8 Hz, J
= 8.8 Hz, 2H), 7.29–7.28 (m, 2H), 2.40 (s, 3H), 2.03–2.00 (m, 4H), 1.81–1.60 (m, 8H), 1.34–1.12 (m, 10H). 13C NMR
(100 MHz CDCl3): δ 141.6 (d, JCꢀP = 2.6 Hz), 131.5 (d, JCꢀP = 8.0 Hz), 129.1 (d, JCꢀP = 10.8 Hz), 126.3 (d, JCꢀP = 87.4
Hz), 35.1 (d, JCꢀP = 67.0 Hz), 26.4 (d, JCꢀP = 11.1 Hz), 26.3 (d, JCꢀP = 10.4 Hz), 25.8, 25.5 (d, JCꢀP = 2.2 Hz), 24.6 (d,
JCꢀP = 3.3 Hz), 21.5. 31P NMR (162 MHz CDCl3): δ 46.08. HRMS: Cal. for C19H29OP 304.1956. Found 304.1950. IR:
2933, 2852, 1444, 1207, 1163, 808 cmꢀ1.
Dicyclohexyl(4-methoxyphenyl)phosphine oxide (3t). Purification by chromatography (petroleum ether/EtOAc =
1:2) afforded 3t (60.2 mg, 94%) as a colorless oil. Rf = 0.53 (EtOAc); 1H NMR (400 MHz CDCl3): δ 7.59 (dd, J = 8.8
Hz, J = 8.8 Hz, 2H), 6.99 (dd, J = 8.8 Hz, J = 1.2 Hz, 2H), 3.85 (s, 3H), 2.04–1.97 (m, 4H), 1.81–1.61 (m, 8H), 1.34–
1.09 (m, 10H). 13C NMR (100 MHz CDCl3): δ 161.9 (d, JCꢀP = 2.7 Hz), 133.1 (d, JCꢀP = 8.7 Hz), 120.7 (d, JCꢀP = 90.6
Hz), 113.8 (d, JCꢀP = 11.2 Hz), 55.2, 35.2 (d, JCꢀP = 67.4 Hz), 26.4 (d, JCꢀP = 12.5 Hz), 26.3 (d, JCꢀP = 11.9 Hz), 25.8 (d,
JCꢀP = 0.6 Hz), 25.5 (d, JCꢀP = 2.3 Hz), 24.6 (d, JCꢀP = 3.2 Hz). 31P NMR (162 MHz CDCl3): δ 45.75. This compound is
known. 22
Dicyclohexyl(4-fluorophenyl)phosphine oxide (3u). Purification by chromatography (petroleum ether/EtOAc = 2:1)
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afforded 3a (58.6 mg, 95%) as a white solid. Rf = 0.55 (EtOAc); m.p.: 133–135 C; H NMR (400 MHz CDCl3): δ
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7.62–7.56 (m, 2H), 7.13–7.09 (m, 2H), 1.96–1.91 (m, 4H), 1.78–1.52 (m, 8H), 1.24–1.02 (m, 10H). 13C NMR (100
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MHz CDCl3): δ 163.8 (dd, JCꢀP = 3.1 Hz, JCꢀF = 250.6 Hz), 132.7 (dd, JCꢀP = 8.0 Hz, JCꢀF = 8.0 Hz), 124.5 (dd, JCꢀP
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86.4 Hz, JCꢀF = 3.7 Hz), 114.7 (d, JCꢀP = 9.7 Hz, JCꢀF = 11.3 Hz), 34.2 (d, JCꢀP = 67.2 Hz), 25.4 (d, JCꢀP = 12.2 Hz), 25.3
(d, JCꢀP = 11.9 Hz), 24.8 (d, JCꢀP = 1.1 Hz), 24.5 (d, JCꢀP = 2.5 Hz), 23.6 (d, JCꢀP = 3.3 Hz). 31P NMR (162 MHz CDCl3):
δ 45.32. HRMS: Cal. for C18H26OFP 308.1705. Found 308.1693. IR: 2927, 2852, 1593, 1500, 1228, 1163 cmꢀ1.
4-(Dicyclohexylphosphoryl)benzonitrile (3v). Purification by chromatography (petroleum ether/EtOAc = 1:2)
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afforded 3a (61.8 mg, 98%) as a yellow oil. Rf = 0.55 (EtOAc); H NMR (400 MHz CDCl3): δ 7.83–7.77 (m, 4H),
2.07–2.05 (m, 4H), 1.86–1.57 (m, 8H), 1.36–1.11 (m, 10H). 13C NMR (100 MHz CDCl3): δ 136.2 (d, JCꢀP = 79.5 Hz),
132.1 (d, JCꢀP = 7.6 Hz), 131.7 (d, JCꢀP = 10.1 Hz), 118.0 (d, JCꢀP = 0.4 Hz), 115.1 (d, JCꢀP = 2.9 Hz), 35.2 (d, JCꢀP = 66.7
Hz), 26.3 (d, JCꢀP = 9.9 Hz), 26.2 (d, JCꢀP = 9.4 Hz), 25.7 (d, JCꢀP = 1.0 Hz), 25.5 (d, JCꢀP = 2.6 Hz), 24.6 (d, JCꢀP = 3.3
Hz). 31P NMR (162 MHz CDCl3): δ 46.39. HRMS: Cal. for C19H26ONP 315.1752. Found 315.1742. IR: 3493, 3423,
2229, 1649, 1444, 1392, 1211, 1105 cmꢀ1.
AUTHOR INFORMATION
Corresponding Author
*Eꢀmail: chentieqiao@hnu.edu.cn
*Eꢀmail: libiaoꢀhan@aist.go.jp
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Partial financial supports from NFSC (21403062, 21573064, 21373080), HNNSF 2015JJ3039 and the Fundamental
Research Funds for the Central Universities (Hunan University) are gratefully acknowledged.
SUPPORTING INFORMATION
1
Copies of H, 13C and 31P NMR spectra and IR spectra. This material is available free of charge via the Internet at
http://pubs.acs.org.
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(4) (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T. Tetrahedron Lett. 1980, 21, 3595; (b) Hirao, T.; Masunaga, T.;
Ohshiro, Y.; Agawa, T. Synthesis 1981, 56.
(5) For reviews, see (a) Tobisu, M.; Chatani, N. Acc. Chem. Res. 2015, 48, 1717; (b) Tasker, S. Z.; Standley, E. A.;
Jamison, T. F. Nature 2014, 509, 299; (c) Yamaguchi, J.; Muto, K.; Itami, K. Eur. J. Org. Chem. 2013, 19; (d) Cornella,
J.; Zarate, C.; Martin, R. Chem. Soc. Rev. 2014, 43, 8081; (e) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.;
Resmerita, A.ꢀM.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346; (f) Yu, D.ꢀG.; Li, B.ꢀJ.; Shi, Z.ꢀJ. Acc. Chem.
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(6) Selected examples of C–C bonds formation via phenol derivatives: (a) Tobisu, M.; Shimasaki, T.; Chatani, N.
Angew. Chem. Int. Ed. 2008, 47, 4866; (b) Wenkert, E.; Michelotti, E. L.; Swindell, C. S.; J. Am. Chem. Soc. 1979, 101,
2246; (c) Quasdorf, K. W.; AntoftꢀFinch, A.; Liu, P.; Silberstein, A. L.; Komaromi, A.; Blackburn, T.; Ramgren, S. D.;
Houk, K. N.; Snieckus, V.; Garg, N. K. J. Am. Chem. Soc. 2011, 133, 6352; (d) Yu, D.ꢀG.; Shi, Z.ꢀJ. Angew. Chem. Int.
Ed. 2011, 50, 7097; (e) Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem. Soc. 2012, 134, 169; (f) Ehle, A. R.; Watson,
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(7) Selected examples of carbonꢀheteroatom bond formation via CꢀO activation: (a) Zarate, C.; Martin, R. J. Am.
Chem. Soc. 2014, 136, 2236; (b) Hie, L.; Ramgren, S. D.; Mesganaw, T.; Garg, N. K. Org. Lett. 2012, 14, 4182; (c)
Huang, K.; Yu, D.ꢀG.; Zheng, S.ꢀF.; Wu, Z.ꢀH.; Shi, Z.ꢀJ. Chem. Eur. J. 2011, 17, 786; (d) Mesganaw, T.; Silberstein, A.
L.; Ramgren, S. D.; Nathel, N. F. F.; Hong, X.; Liu, P.; Garg, N. K. Chem. Sci. 2011, 2, 1766; (e) Shimasaki, T.; Tobisu,
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(8) Yang, J.; Chen, T.; Han, L.ꢀB. J. Am. Chem. Soc. 2015, 137, 1782.
(9) For C–P bond formation, see: (a) Zhao, Y.ꢀL.; Wu, G.ꢀJ.; Han, F.ꢀS. Chem. Commun. 2012, 48, 5868; (b) Wang, T.;
Sang, S.; Liu, L.; Qiao, H.; Gao, Y.; Zhao, Y. J. Org. Chem. 2014, 79, 608; (c) Chen, T.; Zhang, J.ꢀS.; Han, L.ꢀB.
Dalton Trans. 2016, 45, 1843 and references cited therein. For CꢀP formation via highly reactive CꢀO activation: (d)
Holt, D. A.; Erb, J. M. Tetrahedron Lett. 1989, 30, 5393, also see Ref. 9a. Ref. 9a deals with the Niꢀcatalyzed
construction of C–P bonds from electronꢀdeficient phenols via cleavage of the aryl C–O bonds (highly reactive), which
were in situ generated from the electronꢀdeficient phenols with the special PyBroP.
(10) As reported for CꢀO activation, the phenylꢀbased derivatives generally showed lower reactivity than the
naphthylꢀbased derivatives, see Ref.s 5a and 6e. Along this line, by elevating the reaction temperature and employing a
stronger base, we achieved the cross coupling between phenylꢀbased derivatives and P(O)ꢀH compounds, producing
the corresponding aryl phosphorus compounds in good to high yields. Compared with Ref. 8, the solvent was also
changed to toluene, and the starting material Hꢀphosphonates was added in two portions in the present catalytic system.
Those measures may decrease the decomposition (hydrolysis) of Hꢀphosphonates.
(11) The result perhaps was due to the lower solubility of base in toluene, which decreased the decomposition
(hydrolysis) of Hꢀphosphonates. The base also played an important role in the CꢀO activation, see: Xu, H.; Muto, K.;
Yamaguchi, J.; Zhao, C.; Itami, K.; Musaev, D. G. J. Am. Chem. Soc. 2014, 136, 14834.
(12) Low temperature led to difficulty for CꢀO activation, whereas high temperature led to severe decomposition
(hydrolysis) of Hꢀphosphonates.
(13) The reaction with 5 mol% Ni(COD)2 was also performed, however low yield of 3a (40% yield) was given under
similar reaction conditions.
(14) We performed the reaction in 2.0 mmol scale, 82% yield of 3a was obtained.
(15) These results perhaps were due to the slight decomposition of Hꢀphosphonates (hydrolysis) in the presence of a
base. The guess was further supported by the experiment: when the easily hydrolyzed dimethyl phosphonate was
employed as the substrate under the reaction conditions, no expected product was detected.
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(16) For oxidative addition of Ni(0) complex to CArꢀO bond, see: (a) Muto, K.; Yamaguchi, J.; Lei, A.; Itami, K. J. Am.
Chem. Soc. 2013, 135, 16384; (b) Takise, R.; Muto, K.; Yamaguchi, J.; Itami, K. Angew. Chem. Int. Ed. 2014, 53, 6791;
For computational mechanistic insights into the nickelꢀcatalyzed CꢀO activation, see: (c) Hong, X.; Liang, Y.; Houk, K.
N. J. Am. Chem. Soc. 2014, 136, 2017; (d) Lu, Q.; Yu, H.; Fu, Y. J. Am. Chem. Soc. 2014, 136, 8252. For similar ligand
exchange of palladium complexes with ZꢀH (Z = P(O), C) compounds, see: (e) Yang, J.; Chen, T.; Zhou, Y.; Yin, S.;
Han, L.ꢀB. Organometallics 2015, 34, 5095; (f) Chen, T.; Guo, C.; Goto, M.; Han, L.ꢀB. Chem. Commun. 2013, 49,
7498.
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