P-Arylation of Dialkyl Phosphites and Secondary Phosphine Oxides with Arynes

Article abstract of DOI:10.1021/acs.joc.5b02308

The novel P-arylation of dialkyl phosphites and secondary phosphine oxides with arynes has been achieved. The reactions produce dialkyl arylphosphonates in 71-99% yield and tertiary phosphine oxides in 68-92% yield under mild conditions.

Full text of DOI:10.1021/acs.joc.5b02308

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Note
P-Arylation of Dialkyl Phosphites and
Secondary Phosphine Oxides with Arynes
Qian Chen, Xinxing Yan, Zhiyun Du, Kun Zhang, and Chunxiao Wen
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02308 • Publication Date (Web): 09 Dec 2015
Downloaded from http://pubs.acs.org on December 10, 2015
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The Journal of Organic Chemistry
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PꢀArylation of Dialkyl Phosphites and Secondary
Phosphine Oxides with Arynes
Qian Chen,* Xinxing Yan, Zhiyun Du, Kun Zhang, and Chunxiao Wen
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou,
Guangdong 510006, China
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RECEIVED DATE (will be automatically inserted after manuscript is accepted).
O
P
O
P
R2
R2
R1O
R1O
H
H
O
P
OTf
O
P
R2
R2
OR1
OR1
R
CsF, Cs2CO3
CH3CN, 80 oC
CsF, Cs2CO3
CH3CN, 25 oC
R
R
TMS
R2 = Ar, alkyl
68-92% yield
11 examples
R1 = alkyl
71-99% yield
16 examples
ABSTRACT: The novel Pꢀarylation of dialkyl phosphites and secondary phosphine oxides with arynes
has been achieved. The reactions produce dialkyl arylphosphonates in 71–99% yield and tertiary
phosphine oxides in 68–92% yield under mild conditions.
Organophosphorus compounds have been of particular interest due to their broad applications
in organic synthesis,1 materials,2 bioorganic and medical chemistry,3 coordination chemistry and
catalysis,4 and flame retardants.5 The synthesis of various organophosphorus compounds has
been well documented. For examples, the Michaelis–Arbuzov reaction provides an efficient
protocol for the synthesis of alkylphosphonates,6 and the transitionꢀmetalꢀcatalyzed Arbuzov or
Hirao C–P bond construction reaction has been developed for the synthesis of arylphosphonates
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and their derivatives.7 It is noteworthy that trivalent arylphosphines, which have been widely
used in metalꢀcatalyzed reactions as ligands8 and organic synthesis,9 can be facilely prepared by
a reduction of phosphine oxides.10
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Scheme 1. PꢀArylation via Arynes Using Kobayashi Precursors
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With the above background and our recent investigations on the behaviors of arynes,11 we
became interested in studying transitionꢀmetalꢀfree Pꢀarylation of organophosphorus compounds
under mild conditions. Arynes undergo facile insertion into various σ–bonds for the formation of
carbon–carbon and carbon–heteroatom bonds due to the strong electrophilicity of the highly
strained carbon–carbon triple bond.12,13 Recently, various transitionꢀmetalꢀfree C–P bond
formation reactions via arynes have been well developed.14–17 In 2010, Jugé and coꢀworkers
reported an arylation of phosphines with arynes generated in situ from 2ꢀ(trimethylsilyl)aryl
triflates (Kobayashi precursors18) for the synthesis of quaternary and Pꢀstereogenic
phosphonium triflates (Scheme 1a).15 In 2013, Mhaske and coꢀworkers reported an arylation of
P(III) nucleophiles for the synthesis of arylꢀphosphonates, ꢀphosphinates, and ꢀphosphine oxides
via the Michaelis–Arbuzov type reaction involving arynes using Kobayashi precursors (Scheme
1b).16 However, to our knowledge, the arylation of dialkyl phosphites and secondary phosphine
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The Journal of Organic Chemistry
oxides with arynes was rarely investigated. Mhaske and coꢀworkers described that the reaction
of diethyl phosphite with benzyne afforded diethyl phenylphosphonate only in trace amounts.16
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It is noteworthy that Jugé and coꢀworkers recently described one example of the
Oꢀ
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bromophenylation of a secondary phosphine oxide using 1,2ꢀdibromobenzene as the aryne
9
o
precursor with
n
ꢀBuLi at
–
78 C.17 Herein, we report a novel Pꢀarylation of dialkyl phosphites
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and secondary phosphine oxides with arynes, which affords dialkyl arylphosphonates and
tertiary phosphine oxides in good to high yields under mild conditions (Scheme 1c). In addition,
the reaction mechanism has also been investigated.
We first carried out the reactions of Kobayashi benzyne precursor 1a with diethyl phosphite 2a in the
o
presence of CsF or KF/18ꢀcrownꢀ6 in CH3CN or THF at room temperature (25 C), while the desired
diethyl phenylphosphonate 3a was obtained in poor yields. We then turned to the addition of inorganic
bases based on previous research19 and our recent study11b, which described that a few aryne reactions
required their promotion. Thus, we envisioned that the addition of an inorganic base would enhance the
nucleophilicity of dialkyl phosphites. To test this hypothesis, we then examined the reaction of 1a with
2a in the presence of CsF with the addition of Cs2CO3. To our delight, the yield of 3a significantly
increased. With Cs2CO3 (1 equiv) as the base and CsF (5 equiv) as the fluoride source, the reaction of
o
diethyl phosphite 2a with benzyne precursor 1a (2 equiv) in CH3CN at 25 C for 24 h afforded diethyl
phenylphosphonate 3a in a maximum 85% isolated yield (Table 1).
We then set out to explore the generality of this method for Pꢀarylation of dialkyl phosphites with
aryne precursors under the optimized conditions. The reactions of various arynes (generated from aryne
precursors 1a–h) with a variety of dialkyl phosphites 2 led to the formation of the desired products 3b–p
in 71–99% yields (Table 1), whereas treatment of diphenyl phosphite with 1a gave the corresponding
product in poor yield (<5%). To our surprise, Pꢀarylation with an unsymmetrical aryne generated from 4ꢀ
methoxyꢀ2ꢀ(trimethylsilyl)phenyl triflate 1d regioselectively afforded the para isomer (3k or 3l) as a
single product. In contrast, Pꢀarylation with similarly unsymmetrical aryne (generated from 1e or 1f)
produced 3m or 3n with two regioisomers (metaꢀ3/paraꢀ3 = 2:1), which is in good agreement with our
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recent studies on the insertion of arynes into the C−H and O−H bond.11a,b Similarly, both aryne
precursor 1g for 1,2ꢀdidehydronaphthalene and 4,6ꢀdimethylꢀsubstituted aryne precursor 1h afforded the
desired products 3o (α/β = 2:1) and 3p/3p′ (1:4) with two regioisomers, respectively, which further
suggested that these reactions involved an aryne mechanism. In contrast, the previously reported Pꢀ
arylation of triethyl phosphite with 1g gave the βꢀisomer (α/β = 1:40) regioselectively.16 This difference
in regioselectivity might be explained by the steric hindrance of the bulky triethyl phosphite.
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Table 1. Scope of the Reactions of Dialkyl Phosphites with Arynesa,b,c
CsF (5 equiv)
Cs2CO3 (1 equiv)
OTf
O
P
O
P
R1O
R1O
OR1
OR1
+
R
H
CH3CN, 25 oC
TMS
1 (2 equiv)
R
3
2 (1 equiv)
entry
aryne precursor
product(s), yield
O
R
R
OTf
OR1
R
P
OR1
TMS
R
1a, R = H
1b, R = Me
1
2
3
4
5
6
7
8
3a, R = H, R1 = Et, (85%)
3b, R = H, R1 = Me, (83%)
3c, R = H, R1 = iPr, (71%)
3d, R = H, R1 = Bu, (88%)
3e, R = H, R1 = iBu, (99%)
3f, R = H, R1 = Bn, (78%)
3g, R = Me, R1 = Et, (75%)
3h, R = Me, R1 = iBu, (80%)
Me
Me
OTf
O
OR1
OR1
9
3i, R1 = Et, (77%)
3j, R1 = iBu, (84%)
P
TMS
1c
10
Me
Me
OR1
OTf
O
P
OR1
R
R
TMS
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12
13
14
3k, R = OMe, R1 = Et, (85%, para only)
3l, R = OMe, R1 = iBu, (97%, para only)
3m, R = Me, R1 = iBu, (98%, m/p = 2:1)
3n, R = tBu, R1 = iBu, (97%, m/p = 2:1)
1d: R = OMe
1e: R = Me
1f: R = tBu
TMS
OTf
O
OiBu
OiBu
O
+
OiBu
OiBu
P
P
1g
15
3o, (86%,
/
= 2:1)
Me
Me
O
P
O
OiBu
OiBu
OiBu
OiBu
OTf
TMS
Me
P
+
3p'
3p
Me
(98%, 3p/3p' = 1:4)
Me
Me
1h
16
aReaction conditions: 1 (0.68 mmol), 2 (0.34 mmol), CsF (1.7 mmol), Cs2CO3 (0.34 mmol), CH3CN (3.4 mL), 24−48 h.
bIsolated yield based on 2. cIsomer ratio was determined by 1H or 31P NMR.
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The Journal of Organic Chemistry
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Table 2. Scope of the Reactions of Secondary Phosphine Oxides with Arynesa,b
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entry
1
R1
aryne precursor product yield (%)
phenyl
1a
1b
1c
1a
1b
1c
1a
1b
1c
1a
1a
5a
5b
5c
5d
5e
5f
84
80
68
90
84
79
82
72
79
92
85
2
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4
4ꢀMeꢀphenyl
5
6
7
3,5ꢀdimethylꢀphenyl
5g
5h
5i
8
9
10
butyl
5j
11
cyclopentyl
5k
aReaction conditions: 1 (0.68 mmol), 2 (0.34 mmol), CsF (1.7 mmol), Cs2CO3 (1.0 mmol), CH3CN (3.4 mL), 15 h.
bIsolated yield based on 4.
Having succeeded in Pꢀarylation of dialkyl phosphites, we were encouraged to explore the Pꢀ
arylation of secondary phosphine oxides. However, the reaction of diphenylphosphine oxide 4a
with benzyne precursor 1a under the same conditions gave the desired triphenylphosphine oxide
5a in only 19% yield. When the reaction was carried out with excess amounts of Cs2CO3 (3
o
equiv) at 80 C, the yield of 5a was significantly increased (84% yield). Thus, the arylation of
diarylphosphine oxides 4a
–c with aryne precursors 1a–c led to the formation of the desired
products 5b in 68–90% yields under the same conditions (Table 2). It is noteworthy that
–
i
sterically hindered triarylphosphine oxides 5h and 5i can be obtained in good yields. Similarly,
the reaction of dialkylphosphine oxide 4d and 4e with benzyne smoothly afforded
dialkyl(phenyl)phosphine oxide 5j and 5k in high yield, respectively.
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To elucidate the hydrogen source of the orthoꢀposition on 3 or 5, we carried out deuterium labeling
studies (Scheme 2a). When 2a or 4a reacted with benzyne in acetonitrileꢀd3, 3aꢀd or 5aꢀd was not
detected. When the reaction was performed with the addition of D2O (2 equiv), the desired product 5a
was formed in 65% yield with 55% D incorporation at the orthoꢀposition, while only trace amounts of
3a were detected under the same conditions. We then carried out the reaction of 1a with 2aꢀd or 4aꢀd,
and the reaction afforded 3a or 5a with no incorporation of D at the orthoꢀposition. These observations
clearly indicated that trace amounts of water in hygroscopic CsF/Cs2CO3 served as the proton source
reacting with aryl anion intermediate 6 formed by the nucleophilic addition of phosphine to benzyne
(Scheme 2b). Similarly, previous Michaelis−Arbuzovꢀtype reaction involving arynes showed that the
hydrated water of TBAF served as the proton source.14c At this point, the base Cs2CO3, which is stronger
than CsF, probably increases the concentration of the P(III) form through the tautomerization of the P(V)
phosphinylidene 2/4.20 The experimental results of the reactions of dialkyl phosphites (up to 99% yield,
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o
o
o
25 C), diphenyl phosphite (<5% yield, 25 C), or diarylphosphine oxides (up to 90% yield, 80 C,
excess Cs2CO3) with benzyne indicate that initial tautomerization rates decrease in the order
Ar2P(O)H/(PhO)2P(O)H > (AlkO)2P(O)H, which are in good agreement with the literature.20b
Scheme 2. Mechanistic Study
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The Journal of Organic Chemistry
(a) Deuterium labeling studies:
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CsF, Cs2CO3
CD3CN
3a, 84% (0% D)
5a, 80% (0% D)
OTf
O
P
R
R
+
H
O
TMS
CsF, Cs2CO3
R 3a, trace
2a, R = OEt
4a, R = Ph
1a
1a
P
5a, 65% (55% D)
R
D2O (2 equiv)
CH3CN
H/D
O
R
CsF, Cs2CO3
CH3CN
3a, 82% (0% D)
5a, 81% (0% D)
+
P
D
9
R
2a-d/4a-d
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(b) Proposed mechanism:
O
O
P
conditions
R
R
R
R
1a
+
P
2/4
H
3/5
CsF
-H+
H
R
R
H
R
R
O
P
H
O
P
O
H2O
R
R
P
6
2'/4'
In conclusion, we have developed a highly efficient Pꢀarylation method of dialkyl phosphites
and secondary phosphine oxides, which provides a facile protocol for the synthesis of
arylphosphonates and tertiary phosphine oxides. This property of arynes should lead to new and
useful applications in organic synthesis.
EXPERIMENTAL SECTION
General Details. All reactions were carried out under an atmosphere of nitrogen using ovenꢀdried
glassware and standard syringe/septa techniques. Acetonitrile was distilled from calcium hydride. THF
was distilled from sodium. Petroleum ether refers to the petroleum fraction bp 40−60 °C. Commercial
reagents were used without purification unless otherwise noted. Kobayashi aryne precursors 1 were
prepared according to the literature.18 Flash chromatography was performed using the indicated solvent
1
system on silica gel standard grade 60 (230−400 mesh). H NMR spectra were recorded on a 400 MHz
spectrometer. 13C NMR spectra were recorded on a 100 MHz spectrometer. 31P NMR spectra were
recorded on a 162 MHz spectrometer. Chemical shifts are reported relative to CDCl3 (δ 7.26 ppm) for
13
1H NMR and CDCl3 (δ 77.0 ppm) for C NMR. Highꢀresolution mass spectra (HRMS) were recorded
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on ESIꢀTOF. Melting points are uncorrected. The known compounds 3a,16 3b,16 3c,7c 3d,16 3e,21 3f,7c
3g,7d 3i,16 3k,7c 5a,16 5c,16 5d,7g 5g,7f and 5j22 showed characterization data in full agreement with
previously reported data.
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General Procedure for the Synthesis of Dialkyl Arylphosphonates 3. To a solution of 2ꢀ
(trimethylsilyl)phenyl triflate 1a (203 mg, 0.68 mmol) and diethyl phosphite 2a (47 mg, 0.34 mmol) in
acetonitrile (3.4 mL) was added cesium carbonate (111 mg, 0.34 mmol) and cesium fluoride (258 mg,
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o
1.7 mmol) under nitrogen atmosphere. The mixture was stirred at 25 C for 24 h. After removal of the
solvent, the residue was then purified by flash column chromatography on silica gel with petroleum
ether/ethyl acetate (2:1) to give the pure product 3a (62 mg, 85%).
General Procedure for the Synthesis of Tertiary Phosphine Oxides 5. To a solution of 2ꢀ
(trimethylsilyl)phenyl triflate 1a (203 mg, 0.68 mmol) and diphenylphosphine oxide 4a (69 mg, 0.34
mmol) in acetonitrile (3.4 mL) was added cesium carbonate (326 mg, 1.0 mmol) and cesium fluoride
o
(258 mg, 1.7 mmol) under nitrogen atmosphere. The mixture was stirred at 80 C for 15 h. After
removal of the solvent, the residue was then purified by flash column chromatography on silica gel with
petroleum ether/ethyl acetate (2:1) to give the pure product 5a (79 mg, 84%).
Diethyl phenylphosphonate (3a). Thick oil (62 mg, 85%):16 1H NMR (400 MHz, CDCl3) δ 7.85–
13
7.75 (m, 2H), 7.57–7.52 (m, 1H), 7.50–7.42 (m, 2H), 4.20–4.01 (m, 4H), 1.31 (t, J = 7.1 Hz, 6H); C
NMR ( 100 MHz, CDCl3) δ 132.6 (CH, d, J = 3.0 Hz), 131.9 (CH, d, J = 9.9 Hz), 128.4 (CH, d, J = 14.7
Hz), 128.6 (C, d, J = 187 Hz), 62.3 (CH2, d, J = 6.0 Hz), 16.4 (CH3, d, J = 6.4 Hz); 31P NMR (162 MHz,
CDCl3) δ 18.8.
Dimethyl phenylphosphonate (3b). Thick oil (52 mg, 83%):16 1H NMR (400 MHz, CDCl3) δ 7.84–
13
7.77 (m, 2H), 7.60–7.54 (m, 1H), 7.51–7.46 (m, 2H), 3.76 (d, J = 11.1 Hz, 6H); C NMR (100 MHz,
CDCl3) δ 132.3 (CH, d, J = 3.1 Hz), 131.6 (CH, d, J = 9.8 Hz), 128.2 (CH, d, J = 15.1 Hz), 126.7 (C, d,
J = 189 Hz), 52.4 (CH3, d, J = 5.5 Hz); 31P NMR (162 MHz, CDCl3) δ 21.6.
Diisopropyl phenylphosphonate (3c). Thick oil (58 mg, 71%):7c 1H NMR (400 MHz, CDCl3) δ
7.86–7.75 (m, 2H), 7.57–7.48 (m, 1H), 7.48–7.40 (m, 2H), 4.81–4.56 (m, 2H), 1.36 (d, J = 6.2 Hz, 6H),
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The Journal of Organic Chemistry
13
1.21 (d, J = 6.2 Hz, 6H); C NMR (100 MHz, CDCl3) δ 131.9 (CH, d, J = 3.0 Hz), 131.7 (CH, d, J =
9.8 Hz), 130.0 (C, d, J = 188 Hz), 128.3 (CH, d, J = 15.0 Hz), 70.7 (CH, d, J = 5.6 Hz), 24.1 (CH3, d, J
= 4.0 Hz), 23.8 (CH3, d, J = 4.8 Hz); 31P NMR (162 MHz, CDCl3) δ 16.6.
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3
4
5
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Dibutyl phenylphosphonate (3d). Thick oil (81 mg, 88%):16 1H NMR (400 MHz, CDCl3) δ 7.84–
7.76 (m, 2H), 7.54–7.52 (m, 1H), 7.46–7.42 (m, 2H), 4.12–3.95 (m, 4H), 1.69–1.60 (m, 4H), 1.39 (m,
4H), 0.90 (t, J = 7.4 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 132.3 (CH, d, J = 3.0 Hz), 131.7 (CH, d, J
= 9.7 Hz), 128.4 (CH, d, J = 15.4 Hz), 128.3 (C, d, J = 188 Hz), 65.8 (CH2, d, J = 5.7 Hz), 32.4 (CH2, d,
J = 6.5 Hz), 18.7 (CH2), 13.5 (CH3); 31P NMR (162 MHz, CDCl3) δ 18.8.
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Diisobutyl phenylphosphonate (3e). Thick oil (91 mg, 99%):21 1H NMR (400 MHz, CDCl3) δ 7.83–
7.77 (m, 2H), 7.58–7.51 (m, 1H), 7.48–7.43 (m, 2H), 3.91–3.71 (m, 4H), 1.99–1.89 (m, 2H), 0.92 (dd, J
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= 6.7, 1.8 Hz, 12H); C NMR (100 MHz, CDCl3) δ 132.2 (CH, d, J = 3.0 Hz), 131.7 (CH, d, J = 9.7
Hz), 129.3 (C, d, J = 188 Hz), 128.4 (CH, d, J = 15.0 Hz), 71.9 (CH2, d, J = 6.0 Hz), 29.2 (CH, d, J =
6.7 Hz), 18.7 (CH3, d, J = 0.9 Hz); 31P NMR (162 MHz, CDCl3) δ 18.5.
Dibenzyl phenylphosphonate (3f). Thick oil (90 mg, 78%):7c 1H NMR (400 MHz, CDCl3) δ 7.86–
7.80 (m, 2H), 7.58–7.51 (m, 1H), 7.46–7.42 (m, 2H), 7.34–7.27 (m, 10H), 5.14–5.02 (m, 4H); 13C NMR
(100 MHz, CDCl3) δ 136.2 (CH, d, J = 6.9 Hz), 132.4 (CH, d, J = 3.1 Hz), 131.8 (CH, d, J = 10.0 Hz),
128.8 (C, d, J = 190 Hz), 128.6 (CH), 128.4 (CH), 128.3 (CH, d, J = 15.0 Hz), 127.9 (C, d, J = 189 Hz),
67.5 (CH2, d, J = 5.4 Hz); 31P NMR (162 MHz, CDCl3) δ 19.7.
Diethyl (3,4ꢀdimethylphenyl)phosphonate (3g). Thick oil (62 mg, 75%):7d 1H NMR (400 MHz,
CDCl3) δ 7.57 (d, J = 13.2 Hz, 1H), 7.52 (dd, J = 13.3, 7.8 Hz, 1H), 7.21 (dd, J = 7.7, 4.4 Hz, 1H), 4.17–
3.98 (m, 4H), 2.29 (s, 6H), 1.30 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 141.6 (C, d, J = 3.3
Hz), 136.9 (C, d, J = 15.3 Hz), 132.8 (CH, d, J = 10.5 Hz), 129.7 (CH, d, J = 15.8 Hz), 129.3 (CH, d, J
= 9.7 Hz), 125.3 (C, d, J = 189 Hz), 61.9 (CH2, d, J = 5.3 Hz), 19.9 (CH3), 19.6 (CH3), 16.3 (CH3, d, J =
6.5 Hz); 31P NMR (162 MHz, CDCl3): δ 19.9.
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Diisobutyl (3,4ꢀdimethylphenyl)phosphonate (3h). Thick oil (81 mg, 80%): H NMR (400 MHz,
CDCl3) δ 7.56 (d, J = 13.2 Hz, 1H), 7.50 (dd, J = 11.8, 7.6 Hz, 1H), 7.20 (dd, J = 7.7, 4.4 Hz, 1H), 3.86–
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3.69 (m, 4H), 2.29 (s, 6H), 1.97–1.90 (m, 2H), 0.91 (dd, J = 6.7, 2.0 Hz, 12H); C NMR (100 MHz,
CDCl3) δ 141.8 (C, d, J = 3.2 Hz), 136.8 (C, d, J = 15.4 Hz), 132.9 (CH, d, J = 10.4 Hz), 129.7 (CH, d, J
= 15.7 Hz), 129.3 (CH, d, J = 9.5 Hz), 125.3 (C, d, J = 190 Hz), 71.8 (CH2, d, J = 6.0 Hz), 29.2 (CH, d,
J = 6.8 Hz), 19.9 (CH3), 19.6 (CH3), 18.7 (CH3); 31P NMR (162 MHz, CDCl3) δ 19.6; HRMS (ESIꢀTOF)
m/z: [M + Na]+ Calcd for C16H27PO3Na 321.1590; Found 321.1595.
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Diethyl (2,5ꢀdimethylphenyl)phosphonate (3i). Thick oil (63 mg, 77%):16 1H NMR (400 MHz,
CDCl3) δ 7.74 (d, J = 14.7 Hz, 1H), 7.22 (d, J = 7.7 Hz, 1H), 7.16–7.10 (m, 1H), 4.21–3.99 (m, 4H),
2.51 (s, 3H), 2.33 (s, 3H), 1.32 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 138.5 (C, d, J = 10.0
Hz), 134.9 (C, d, J = 14.9 Hz), 134.5 (CH, d, J = 10.5 Hz), 133.1 (CH, d, J = 3.1 Hz), 131.1 (CH, d, J =
15.7 Hz), 126.4 (C, d, J = 183 Hz), 61.8 (CH2, d, J = 5.4 Hz), 20.9 (CH3), 20.6 (CH3), 16.3 (CH3, d, J =
6.5 Hz); 31P NMR (162 MHz, CDCl3) δ 20.0.
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Diisobutyl (2,5ꢀdimethylphenyl)phosphonate (3j). Thick oil (85 mg, 84%): H NMR (400 MHz,
CDCl3) δ 7.75 (d, J = 16.2 Hz, 1H), 7.22 (d, J = 7.7 Hz, 1H), 7.16–7.10 (m, 1H), 3.88–3.71 (m, 4H),
2.51 (s, 3H), 2.34 (s, 3H), 1.98–1.91 (m, 2H), 0.93 (d, J = 6.7 Hz, 12H); 13C NMR (100 MHz, CDCl3) δ
138.5 (C, d, J = 9.8 Hz), 134.9 (C, d, J = 14.9 Hz), 134.6 (CH, d, J = 10.5 Hz), 133.1 (CH, d, J = 3.1
Hz), 131.1 (CH, d, J = 15.6 Hz), 126.4 (C, d, J = 182 Hz), 71.7 (CH2, d, J = 6.1 Hz), 29.2 (CH, d, J =
6.9 Hz), 20.8 (CH3), 20.7 (CH3, d, J = 3.4 Hz), 18.8 (CH3); 31P NMR (162 MHz, CDCl3) δ 20.2; HRMS
(ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H27PO3Na 321.1590; Found 321.1595.
Diethyl (4ꢀmethoxyphenyl)phosphonate (3k). Thick oil (70 mg, 85%):7c 1H NMR (400 MHz,
CDCl3) δ 7.74 (dd, J = 12.7, 8.7 Hz, 2H), 6.99–6.94 (m, 2H), 3.84 (s, 3H), 1.30 (t, J = 7.1 Hz, 6H); 13C
NMR (100 MHz, CDCl3) δ 162.8 (C, d, J = 3.4 Hz), 133.7 (CH, d, J = 11.3 Hz), 119.6 (C, d, J = 195
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Hz), 114.0 (CH, d, J = 16.0 Hz), 61.9 (CH2, d, J = 6.5 Hz), 55.3 (CH3), 16.3 (CH3, d, J = 6.5 Hz); P
NMR (162 MHz, CDCl3) δ 19.7.
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Diisobutyl (4ꢀmethoxyphenyl)phosphonate (3l). Thick oil (99 mg, 97%): H NMR (400 MHz,
CDCl3) δ 7.73 (dd, J = 14.9, 9.1 Hz, 2H), 6.96 (dd, J = 11.7, 2.9 Hz, 2H), 3.84 (s, 3H), 3.83–3.69 (m,
4H), 1.96–1.90 (m, 2H), 0.91 (dd, J = 6.7, 2.0 Hz, 12H); 13C NMR (100 MHz, CDCl3) δ 162.8 (C, d, J =
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3.4 Hz), 133.7 (CH, d, J = 11.2 Hz), 119.6 (C, d, J = 196 Hz), 113.4 (CH, d, J = 16.0 Hz), 71.8 (CH2, d,
J = 6.0 Hz), 55.3 (CH3), 29.2 (CH, d, J = 6.5 Hz), 18.7 (CH3, d, J = 1.3 Hz); 31P NMR (162 MHz,
CDCl3) δ 19.4; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H25PO4Na 323.1383; Found 323.1390.
Diisobutyl mꢀtolylphosphonate (mꢀ3m) and diisobutyl pꢀtolylphosphonate (pꢀ3m). Thick oil (95
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mg, 98%). Two isomers in ~2:1 ratio: H NMR (400 MHz, CDCl3) mꢀ3m: δ 7.62 (d, J = 13.7 Hz, 1H),
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7.56 (dd, J = 7.2, 1.6 Hz, 1H), 7.34 (dd, J = 5.3, 4.2 Hz, 2H), 3.85–3.69 (m, 4H), 2.39 (s, 3H), 2.02–1.87
(m, 2H), 0.91 (dd, J = 6.7, 2.0 Hz, 12H); pꢀ3m: δ 7.68 (dd, J = 13.1, 8.1 Hz, 2H), 7.29–7.24 (m, 2H),
3.86–3.71 (m, 4H), 2.39 (s, 3H), 2.02–1.87 (m, 2H), 0.92 (dd, J = 6.7, 2.0 Hz, 12H); 13C NMR (100
MHz, CDCl3) mꢀ3m: δ 138.2 (C, d, J = 15.0 Hz), 133.0 (CH, d, J = 3.2 Hz), 132.3 (CH, d, J = 9.9 Hz),
128.8 (CH, d, J = 9.5 Hz), 128.5 (C, d, J = 187 Hz), 128.3 (CH, d, J = 15.7 Hz), 71.9 (CH2, d, J = 6.1
Hz), 29.2 (CH, d, J = 6.7 Hz), 21.6 (CH3), 18.7 (CH3, d, J = 0.9 Hz); pꢀ3m: δ 142.9 (C, d, J = 3.1 Hz),
131.8 (CH, d, J = 10.1 Hz), 129.2 (CH, d, J = 15.4 Hz), 125.1 (C, d, J = 191 Hz), 71.9 (CH2, d, J = 6.1
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Hz), 29.2 (CH, d, J = 6.7 Hz), 21.3 (CH3), 18.7 (CH3, d, J = 0.9 Hz); P NMR (162 MHz, CDCl3) mꢀ
3m: δ 19.0; pꢀ3m: δ 19.3; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C15H25PO3Na 307.1434; Found
307.1438.
Diisobutyl
(3ꢀ(tertꢀbutyl)phenyl)phosphonate
(mꢀ3n)
and
diisobutyl
(4ꢀ(tertꢀ
butyl)phenyl)phosphonate (pꢀ3n). Thick oil (108 mg, 97%). Two isomers in ~2:1 ratio: 1H NMR (400
MHz, CDCl3) mꢀ3n: δ 7.81 (d, J = 15.9 Hz, 1H), 7.61–7.54 (m, 2H), 7.39–7.34 (m, 1H), 3.86–3.72 (m,
4H), 1.98–1.88 (m, 2H), 1.31 (s, 9H), 0.90 (dd, J = 6.5, 1.1 Hz, 12H); pꢀ3n: δ 7.71 (dd, J = 12.9, 8.5 Hz,
2H), 7.47–7.44 (m, 2H), 3.88–3.70 (m, 4H), 2.00–1.86 (m, 2H), 1.32 (s, 9H), 0.91 (dd, J = 6.7, 1.2 Hz,
12H); 13C NMR (100 MHz, CDCl3) mꢀ3n: δ 151.4 (C, d, J = 13.9 Hz), 129.3 (CH, d, J = 3.1 Hz), 128.8
(CH, d, J = 9.6 Hz), 128.6 (CH, d, J = 10.6 Hz), 128.1 (CH, d, J = 15.8 Hz), 127.8 (C, d, J = 186 Hz),
71.8 (CH2, d, J = 6.4 Hz), 31.1 (CH3), 29.1 (CH, d, J = 6.8 Hz), 18.7 (CH3, d, J = 1.6 Hz); pꢀ3n: δ 155.7
(C, d, J = 3.2 Hz), 131.6 (CH, d, J = 10.1 Hz), 125.6 (C, d, J = 189 Hz), 125.4 (CH, d, J = 15.2 Hz),
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71.8 (CH2, d, J = 6.2 Hz), 31.2 (CH3), 29.1 (CH, d, J = 6.8 Hz), 18.7 (CH3, d, J = 1.6 Hz); P NMR
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(162 MHz, CDCl3) mꢀ3n: δ 19.3; pꢀ3n: δ 19.1; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for
C18H31PO3Na 349.1903; Found 349.1900.
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Diisobutyl naphthalenꢀ1ꢀylphosphonate (αꢀ3o) and diisobutyl naphthalenꢀ2ꢀylphosphonate (βꢀ
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3o). Thick oil (94 mg, 86%). Two isomers in ~2:1 ratio: H NMR (400 MHz, CDCl3) αꢀ3o: δ 8.52 (d, J
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= 8.5 Hz, 1H), 8.29–8.20 (m, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 25.1 Hz, 1H), 7.76 (d, J = 19.4
Hz, 1H), 7.59–7.49 (m, 2H), 3.95–3.86 (m, 4H), 2.06–1.89 (m, 2H), 0.94 (dd, J = 6.7, 2.8 Hz, 12H); βꢀ
3o: δ 8.43 (d, J = 15.2 Hz, 1H), 7.98–7.86 (m, 3H), 7.82–7.70 (m, 1H), 7.62–7.49 (m, 2H), 3.82–3.73
(m, 4H), 2.05–1.91 (m, 2H), 0.90 (dd, J = 6.7, 2.4 Hz, 12H); 13C NMR (100 MHz, CDCl3) αꢀ3o: δ 134.6
(C, d, J = 9.1 Hz), 133.6 (C, d, J =1.5 Hz), 133.6 (CH, d, J = 2.7 Hz), 132.7 (CH, d, J = 2.4 Hz), 128.7
(CH, d, J = 1.9 Hz), 128.2 (CH), 127.4 (CH), 126.6 (CH, d, J = 15.4 Hz), 124.7 (C, d, J = 187 Hz),
124.5 (CH, d, J = 16.1 Hz), 72.1 (CH2, d, J = 5.9 Hz), 29.1 (CH, d, J = 6.8 Hz), 18.8 (CH3); βꢀ3o: δ
135.0 (C), 134.0 (C, d, J = 10.2 Hz), 132.4 (CH, d, J = 16.6 Hz), 128.9 (CH), 128.3 (CH, d, J = 18.6
Hz), 128.29 (CH), 127.8 (CH), 126.8 (CH), 126.5 (CH, d, J = 9.8 Hz), 125.4 (C, d, J = 178 Hz), 72.1
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(CH2, d, J = 5.9 Hz), 29.2 (CH, d, J = 6.9 Hz), 18.8 (CH3); P NMR (162 MHz, CDCl3) αꢀ3o: δ 19.1;
βꢀ3o: δ 19.2; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C18H25PO3Na 343.1434; Found 343.1435.
Diisobutyl
(3,5ꢀdimethylphenyl)phosphonate
(3p)
and
diisobutyl
(2,4ꢀ
dimethylphenyl)phosphonate (3p′). Thick oil (99 mg, 98%). Two isomers in ~1:4 ratio: 1H NMR (400
MHz, CDCl3) 3p: δ 7.80 (dd, J = 14.1, 8.3 Hz, 1H), 7.07–7.05 (m, 2H), 3.90–3.68 (m, 4H), 2.53 (s, 3H),
2.35 (s, 3H), 1.99–1.89 (m, 2H), 0.93 (dd, J = 6.7, 1.9 Hz, 12H); 3p′: δ 7.42 (s, 1H), 7.39 (s, 1H), 7.16
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(s, 1H), 3.88–3.70 (m, 4H), 2.35 (s, 6H), 2.00–1.90 (m, 2H), 0.93 (dd, J = 6.7, 1.9 Hz, 12H); C NMR
(100 MHz, CDCl3) 3p: δ 142.8 (C, d, J = 3.1 Hz), 141.6 (C, d, J = 10.6 Hz), 134.1 (CH, d, J = 10.8 Hz),
132.0 (CH, d, J = 15.4 Hz), 126.1 (CH, d, J = 15.3 Hz), 125.1 (C, d, J = 108 Hz), 71.7 (CH2, d, J = 6.1
Hz), 29.3 (CH, d, J = 6.7 Hz), 21.4 (CH3), 21.1 (CH3), 18.7 (CH3); 3p′: δ 138.1 (C, d, J = 15.8 Hz),
134.1 (C, d, J = 3.9 Hz), 129.4 (CH, d, J = 9.7 Hz), 127.9 (C, d, J = 187 Hz), 71.9 (CH2, d, J = 6.0 Hz),
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29.2 (CH, d, J = 6.7 Hz), 21.2 (CH3), 18.7 (CH3, d, J = 0.6 Hz); P NMR (162 MHz, CDCl3) 3p: δ
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20.4; 3p′: δ 19.5; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H27PO3Na 321.1590; Found
321.1595.
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Triphenylphosphine oxide (5a). White amorphous solid (79 mg, 84%):16 1H NMR (400 MHz,
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CDCl3) δ 7.68–7.61 (m, 6H), 7.58–7.52 (m, 3H), 7.51–7.43 (m, 6H); C NMR (100 MHz, CDCl3) δ
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132.6 (C, d, J = 103 Hz), 132.0 (CH, d, J = 9.9 Hz), 131.9 (CH, d, J = 2.7 Hz), 128.5 (CH, d, J = 12.1
Hz); 31P NMR (162 MHz, CDCl3) δ 29.1.
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(3,4ꢀDimethylphenyl)diphenylphosphine oxide (5b). White amorphous solid (83 mg, 80%): mp
113–114 oC; 1H NMR (400 MHz, CDCl3) δ 7.68–7.63 (m, 4H), 7.55–7.49 (m, 3H), 7.47–7.42 (m, 4H),
7.32–7.27 (m, 1H), 7.2–7.19 (m, 1H), 2.30 (s, 3H), 2.27 (d, J = 7.9 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 141.2 (C, d, J = 2.9 Hz), 137.2 (C, d, J = 12.3 Hz), 133.4 (C, d, J = 100 Hz), 133.0 (CH, d, J =
9.8 Hz), 132.0 (CH, d, J = 9.9 Hz), 131.9 (CH, d, J = 2.7 Hz), 129.7 (CH, d, J = 2.8 Hz), 129.9 (C, d, J
= 110 Hz), 129.6 (CH), 128.5 (CH, d, J = 12.1 Hz), 19.9 (CH3), 19.7 (CH3); 31P NMR (162 MHz,
CDCl3) δ 29.4; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C20H19PONa 329.1066; Found 329.1069.
(2,5ꢀDimethylphenyl)diphenylphosphine oxide (5c). White amorphous solid (71 mg, 68%):16 1
H
NMR (400 MHz, CDCl3) δ 7.69–7.62 (m, 4H), 7.56–7.51 (m, 2H), 7.48–7.43 (m, 4H), 7.22 (d, J = 7.8
Hz, 1H), 7.17–7.14 (m, 1H), 6.88 (d, J = 14.4 Hz, 1H), 2.36 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 140.0 (C, d, J = 8.1 Hz), 134.7 (C, d, J = 12.8 Hz), 133.9 (CH, d, J = 12.5 Hz), 132.9 (C, d, J
= 104 Hz), 132.8 (CH, d, J = 2.7 Hz), 131.9 (CH, d, J = 9.7 Hz), 131.8 (CH), 131.7 (CH, d, J = 2.8 Hz),
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130.4 (C, d, J = 103 Hz), 128.5 (CH, d, J = 12.0 Hz), 21.2 (CH3, d, J = 4.7 Hz), 20.9 (CH3); P NMR
(162 MHz, CDCl3) δ 31.7.
Phenyldiꢀpꢀtolylphosphine oxide (5d). White amorphous solid (94 mg, 90%):7g 1H NMR (400 MHz,
CDCl3) δ 7.66–7.61 (m, 2H), 7.55–7.47 (m, 5H), 7.43–7.39 (m, 2H), 7.23 (d, J = 6.6 Hz, 4H), 2.39 (s,
6H); 13C NMR (100 MHz, CDCl3) δ 142.3 (C, d, J = 2.6 Hz), 133.1 (C, d, J = 104 Hz), 132.3 (CH, d, J
= 10.2 Hz), 132.1 (CH, d, J = 10.2 Hz), 131.8 (CH, d, J = 2.5 Hz), 129.3 (C, d, J = 106 Hz), 129.2 (CH,
d, J = 12.5 Hz), 128.4 (CH, d, J = 12.1 Hz), 21.6 (CH3); 31P NMR (162 MHz, CDCl3) δ 29.3.
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(3,4ꢀDimethylphenyl)diꢀpꢀtolylphosphine oxide (5e). White amorphous solid (95 mg, 84%): mp
102–103 oC; 1H NMR (400 MHz, CDCl3) δ 7.56–7.48 (m, 5H), 7.30–7.28 (m, 1H), 7.26–7.23 (m, 4H),
7.20–7.15 (m, 1H), 2.39 (s, 6H), 2.29 (s, 3H), 2.26 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 142.1 (C, d,
J = 2.5 Hz), 140.9 (C, d, J = 6.1 Hz), 137.0 (C, d, J = 12.2 Hz), 133.0 (C, d, J = 9.8 Hz), 132.1 (CH, d, J
= 10.2 Hz), 131.3 (C, d, J = 146 Hz), 130.5 (C, d, J = 106 Hz), 129.7 (CH, d, J = 3.1 Hz), 129.5 (CH, d,
J = 6.0 Hz), 129.1 (CH, d, J = 12.4 Hz), 21.6 (CH3), 19.9 (CH3), 19.7 (CH3); 31P NMR (162 MHz,
CDCl3) δ 29.4; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C22H23PONa 357.1379; Found 357.1383.
(2,5ꢀDimethylphenyl)diꢀpꢀtolylphosphine oxide (5f). White amorphous solid (90 mg, 79%): mp
146–148 oC; 1H NMR (400 MHz, CDCl3) δ 7.54–7.49 (m, 4H), 7.27–7.24 (m, 4H), 7.21 (d, J = 7.7 Hz,
1H), 7.17–7.12 (m, 1H), 6.89 (d, J = 14.2 Hz, 1H), 2.40 (s, 6H), 2.36 (s, 3H), 2.20 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 142.0 (C, d, J = 2.7 Hz), 139.9 (C, d, J = 8.1 Hz), 134.5 (C, d, J = 12.6 Hz), 133.9
(CH, d, J = 12.5 Hz), 132.6 (CH, d, J = 2.5 Hz), 131.9 (CH, d, J = 10.1 Hz), 131.7 (CH, d, J = 11.0 Hz),
130.9 (C, d, J = 102 Hz), 129.9 (C, d, J = 101 Hz), 129.2 (CH, d, J = 12.4 Hz), 21.6 (CH3), 21.2 (CH3, d,
J = 4.6 Hz), 21.0 (CH3); 31P NMR (162 MHz, CDCl3) δ 31.8; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd
for C22H23PONa 357.1379; Found 357.1383.
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Bis(3,5ꢀdimethylphenyl)(phenyl)phosphine oxide (5g). White amorphous solid (93 mg, 82%):7f 1
H
NMR (400 MHz, CDCl3) δ 7.71–7.62 (m, 2H), 7.54–7.50 (m, 1H), 7.47–7.42 (m, 2H), 7.26 (d, J = 12
13
Hz, 4H), 7.16 (s, 2H), 2.31 (s, 12H); C NMR (100 MHz, CDCl3) δ 138.1 (C, d, J = 12.7 Hz), 133.6
(CH, d, J = 2.8 Hz), 132.8 (C, d, J = 103 Hz), 132.1 (C, d, J = 104 Hz), 132.3 (CH, d, J = 9.9 Hz), 131.9
(CH, d, J = 2.7 Hz), 129.6 (CH, d, J = 9.8 Hz), 128.3 (CH, d, J = 12.0 Hz), 21.2 (CH3); 31P NMR (162
MHz, CDCl3) δ 29.7.
(3,4ꢀDimethylphenyl)bis(3,5ꢀdimethylphenyl)phosphine oxide (5h). White amorphous solid (89
o
mg, 72%): mp 90–91 C; 1H NMR (400 MHz, CDCl3) δ 7.51 (d, J = 12.0 Hz, 1H), 7.31–7.25 (m, 5H),
7.20–7.17 (m, 1H), 7.14 (s, 2H), 2.31 (s, 15H), 2.27 (s, 3H);13C NMR (100 MHz, CDCl3) δ 140.8 (C, d,
J = 2.8 Hz), 138.0 (C, d, J = 12.7 Hz), 136.9 (C, d, J = 12.2 Hz), 133.4 (CH, d, J = 2.8 Hz), 133.3 (C, d,
J = 106 Hz), 133.0 (CH, d, J = 9.6 Hz), 130.5 (C, d, J = 104 Hz), 129.6 (CH, d, J = 9.8 Hz), 129.6 (CH,
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d, J = 1.2 Hz), 128.7 (CH, d, J = 11.4 Hz), 21.3 (CH3), 19.9 (CH3), 19.7 (CH3); P NMR (162 MHz,
CDCl3) δ 29.6; HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C24H27PONa 385.1692; Found 385.1698.
(2,5ꢀDimethylphenyl)bis(3,5ꢀdimethylphenyl)phosphine oxide (5i). White amorphous solid (97 mg,
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6
o
1
7
79%): mp 133–134 C; H NMR (400 MHz, CDCl3) δ 7.27–7.11 (m, 8H), 6.88 (d, J = 14.2 Hz, 1H),
2.36 (s, 3H), 2.31 (s, 6H), 2.21 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 139.9 (C, d, J = 8.0 Hz), 138.0
(C, d, J = 12.6 Hz), 134.4 (C, d, J = 12.7 Hz), 133.9 (CH, d, J = 12.6 Hz), 133.4 (CH, d, J = 2.8 Hz),
132.3 (C, d, J = 102 Hz), 132.5 (CH, d, J = 2.6 Hz), 131.6 (CH, d, J = 11.0 Hz), 130.8 (C, d, J = 102
Hz), 129.4 (CH, d, J = 9.7 Hz), 21.3 (CH3), 21.2 (CH3), 21.0 (CH3); 31P NMR (162 MHz, CDCl3) δ 32.1;
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C24H27PONa 385.1692; Found 385.1698.
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Dibutyl(phenyl)phosphine oxide (5j). Thick oil (74 mg, 92%):22 1H NMR (400 MHz, CDCl3) δ
7.71–7.66 (m, 2H), 7.52–7.48 (m, 1H), 7.44–7.37 (m, 2H), 2.36 (br, 2H), 2.08–1.80 (m, 4H), 1.57–1.31
(m, 6H), 0.78 (t, J = 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 132.1 (CH, d, J = 2.6 Hz), 131.1 (C, d,
J = 126 Hz), 130.5 (CH, d, J = 9.1 Hz), 128.7 (CH, d, J = 11.4 Hz), 28.8 (CH2, d, J = 69.2 Hz), 23.9
(CH2, d, J = 15.3 Hz), 23.3 (CH2, d, J = 4.0 Hz), 13.3 (CH3); 31P NMR (162 MHz, CDCl3) δ 44.8.
1
Dicyclopentyl(phenyl)phosphine oxide (5k). Thick oil (76 mg, 85%): H NMR (400 MHz, CDCl3)
δ 7.72–7.68 (m, 2H), 7.51–7.46 (m, 1H), 7.42–7.38 (m, 2H), 2.36–2.28 (m, 2H), 2.01–1.76 (m, 4H),
13
1.70–1.41 (m, 12H); C NMR (100 MHz, CDCl3) δ 131.8 (CH, d, J = 2.4 Hz), 131.3 (CH, d, J = 2.4
Hz), 130.1 (C, d, J = 127 Hz), 128.3 (CH, d, J = 10.7 Hz), 37.5 (CH, d, J = 71.2 Hz), 27.0 (CH2), 26.5
(CH2, d, J = 9.6 Hz), 26.0 (CH2), 25.9 (CH2, d, J = 10.0 Hz); 31P NMR (162 MHz, CDCl3) δ 47.3;
HRMS (ESIꢀTOF) m/z: [M + Na]+ Calcd for C16H23PONa 285.1379; Found 285.1385.
Supporting Information
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Copies of H, C and P NMR spectra for 3 and 5. This material is available free of charge via the
Internet at http://pubs.acs.org.
Corresponding Author
*Eꢀmail: qianchen@gdut.edu.cn.
Notes
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by the National Natural Science Foundation of China (21242002) and 100
Young Talents Programme of Guangdong University of Technology (220413506).
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REFERENCES
(1) (a) Kosolapoff, G. M.; Maier, L. Organic Phosphorus Compounds; WileyꢀInterscience: New York, 1972. (b)
Bhattacharya, A. K.; Thyagarajan, G. Chem. Rev. 1981, 81, 415. (c) Tang, W.; Zhang, X. Chem. Rev. 2003, 103,
3029.
(2) (a) Steininger, H.; Schuster, M.; Kreuer, K. D.; Kaltbeitzel, A.; Bingol, B.; Meyer, W. H.; Schauff, S.;
Brunklaus, G.; Maier, J.; Spiess, H. W. Phys. Chem. Chem. Phys. 2007 , 1764. (b) Spampinato, V.; Tuccitto, N.;
Quici, S.; Calabrese, V.; Marletta, G.; Torrisi, A.; Licciardello, A. Langmuir 2010 26, 8400.
(3) (a) Shie, J.ꢀJ.; Fang, J.ꢀM.; Wang, S.ꢀY.; Tsai, K.ꢀC.; Cheng, Y.ꢀS. E.; Yang, A.ꢀS.; Hsiao, S.ꢀC.; Su, C.ꢀY.;
Wong, C.ꢀH. J. Am. Chem. Soc. 2007 129, 11892. (b) Shie, J.; Fang, J.; Wong, C. Angew. Chem. 2008 120, 5872;
Angew. Chem., Int. Ed. 2008 47, 5788. (c) Wydysh, E. A.; Medghalchi, S. M.; Vadlamudi, A.; Townsend, C. A. J.
Med. Chem. 2009 52, 3317.
(4) (a) Pinault, N. Coord. Chem. Rev. 2003
2011 40, 4948. (c) FernándezꢀPérez, H.; Etayo, P.; Panossian, A.; VidalꢀFerran, A. Chem. Rev. 2011
(5) (a) Cho, C.ꢀS.; Chen, L.ꢀW.; Chiu, Y.ꢀS. Polym. Bull. 1998 41, 45. (b) Cho, C.ꢀS.; Fu, S.ꢀC.; Chen, L.ꢀW.; Wu,
T.ꢀR. Polym. Int. 1998 47, 203.
(6) (a) Arbuzov, B. A. Pure Appl. Chem. 1964
,
9
,
,
,
,
,
,
241, 1. (b) Knappke, C. E. I.; von Wangelin, A. J. Chem. Soc. Rev.
111, 2119.
,
,
,
,
,
9
, 307. (b) Bhattacharya, A. K.; Thyagarajan, G. Chem. Rev. 1981
,
,
81, 415. (c) Renard, P.ꢀY.; Vayron, P.; Leclerc, E.; Valleix, A.; Mioskowski, C. Angew. Chem., Int. Ed. 2003, 42
2389.
(7) For recent reviews, see: (a) Jablonkai, E.; Keglevich, G. Curr. Org. Synth. 2014
Keglevich, G. Org. Prep. Proc. Int. 2014 46, 281. For selected examples, see: (c) Zhuang, R.; Xu, J.; Cai, Z.; Tang,
G.; Fang, M.; Zhao, Y. Org. Lett. 2011 13, 2110. (d) Yang, G.; Shen, C.; Zhang, L.; Zhang, W. Tetrahedron Lett.
52, 5032. (e) Keglevich, G.; Grün, A.; Bölcskei, A.; Drahos, L.; Kraszni, M.; Balogh, G. T. Heteroatom Chem.
, 11, 429. (b) Jablonkai, E.;
,
,
2011
2012
,
,
23, 574. (f) Shen, C.; Yang, G.; Zhang, W. Org. Biomol. Chem. 2012
51, 7540.
ACS Paragon Plus Environment
,
10, 3500. (g) Zhang, J.ꢀS.; Chen, T.;
Yang, J.; Han, L.ꢀB. Chem. Commun. 2015
,
16

Page 17 of 18
The Journal of Organic Chemistry
(8) (a) de Meijere, A.; Diederich, F. MetalꢀCatalyzed CrossꢀCoupling Reactions; WileyꢀVCH: Weinheim, 2004. (b)
Börner, A. Phosphorus Ligands in Asymmetric CatalysisꢀSynthesis and Application; WileyꢀVCH: Weinheim, 2008.
(c) Kamer, P. C. J.; van Leeuwen, P. W. N. M. Phosphorus(III) Ligands in Homogeneous Catalysis: Design and
Synthesis; WileyꢀVCH: Chichester, U.K., 2012.
1
2
3
4
5
6
7
8
9
(9) McClure, C. K. Phosphorus in Organic Chemistry; WileyꢀVCH: Weinheim, 2012.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) Li, Y.; Das, S.; Zhou, S.; Junge, K.; Beller, M. J. Am. Chem. Soc. 2012
(11) (a) Chen, Q.; Zhang, C.; Chen, L.; Wen, C.; Du, Z.; Chen, H.; Zhang, K. Tetrahedron Lett. 2015
Wen, C.; Chen, Q.; He, Z.; Yan, X.; Zhang, C.; Du, Z.; Zhang, K. Tetrahedron Lett. 2015 56, 5470. (c) Chen, L.;
Zhang, C.; Wen, C.; Zhang, K.; Liu, W.; Chen, Q. Catal. Commun. 2015 65, 81.
(12) (a) Peña, D.; Pérez, D.; Guitián, E. Angew. Chem., Int. Ed. 2006 45, 3579. (b) Bhunia, A.; Yetra, S. R.; Biju,
A. T. Chem. Soc. Rev. 2012 41, 3140.
(13) For recent examples, see: (a) Dong, Y.; Liu, B.; Chen, P.; Liu, Q.; Wang, M. Angew. Chem., Int. Ed. 2014
3442. (b) Taniguchi, T.; Curran, D. P. Angew. Chem., Int. Ed. 2014 53, 13150. (c) Hendrick, C. E.; Wang, Q. J.
Org. Chem. 2015 80, 1059. (d) GarcíaꢀLópez, J.ꢀA.; Çetin, M.; Greaney, M. F. Org. Lett. 2015 17, 2649. (e) Shi, J.;
Qiu, D.; Wang, J.; Xu, H.; Li, Y. J. Am. Chem. Soc. 2015 137, 5670.
(14) For selected examples, see: (a) Yoshida, H.; Watanabe, M.; Ohshita, J.; Kunai, A. Chem. Lett. 2005
, 134, 9727.
,
56, 2094. (b)
,
,
,
,
,
53,
,
,
,
,
,
34, 1538.
(b) Diemer, V.; Berthelot, A.; Bayardon, J.; Jugé, S.; Leroux, F. R.; Colobert, F. J. Org. Chem. 2012
Yoshida, S.; Hosoya, T. Chem. Lett. 2013 42, 583. (d) Shen, C.; Yang, G.; Zhang, W. Org. Lett. 2013
Bhunia, A.; Kaicharla, T.; Porwal, D.; Gonnade, R. G.; Biju, A. T. Chem. Commun. 2014
Roy, T.; Gonnade, R. G.; Biju, A. T. Org. Lett. 2014 16, 5132. (g) LopezꢀLeonardo, C.; Raja, R.; LópezꢀOrtiz, F.;
,
77, 6117. (c)
,
, 15, 5722. (e)
,
50, 11389. (f) Bhunia, A.;
,
del ÁguilaꢀSánchez, M. Á.; Alajarin, M. Eur. J. Org. Chem. 2014, 1084.
(15) Rémond, E.; Tessier, A.; Leroux, F. R.; Bayardon, J.; Jugé, S. Org. Lett. 2010, 12, 1568.
(16) Dhokale, R. A.; Mhaske, S. B. Org. Lett. 2013
(17) Bayardon, J.; Laureano, H.; Diemer, V.; Dutartre, M.; Das, U.; Rousselin, Y.; Henry, J.ꢀC.; Colobert, F.;
Leroux, F. R.; Jugé, S. J. Org. Chem. 2012 77, 5759.
(18) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983
(19) For selected examples, see: (a) Okuma, K.; Nojima, A.; Matsunaga, N.; Shioji, K. Org. Lett. 2009
, 15, 2218.
,
,
12, 1211.
,
11, 169. (b)
Kivrak, A.; Larock, R. C. J. Org. Chem. 2010
,
75, 7381. (c) Rogness, D. C.; Larock, R. C. J. Org. Chem. 2011 76
,
,
4980.
17
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Page 18 of 18
, 13, 3270.
(20) For P(=O)H to P−OH tautomerism, see: (a) Deal, E. L.; Petit, C.; Montchamp, J.ꢀL. Org. Lett. 2011
1
2
3
4
5
(b) Janesko, B. G.; Fisher, H. C.; Bridle, M. J.; Montchamp, J.ꢀL. J. Org. Chem. 2015
(21) Nitta, Y.; Arakawa, Y. Chem. Pharm. Bull. 1986 34, 3121.
, 80, 10025.
,
6
7
(22) Kendall, A. J.; Salazar, C. A.; Martino, P. F.; Tyler, D. R. Organometallics 2014, 33, 6171.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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