Palladium(II)-catalyzed ortho-arylation of benzylic phosphonic monoesters using potassium aryltrifluoroborates

Article abstract of DOI:10.1021/jo401716p

The new monophosphonic acid directing group was successfully utilized in the Pd (II)-catalyzed ortho-arylation of benzylic phosphonic monoesters using potassium aryltrifluoroborates. A wide range of benzylic phosphonic monoesters underwent clean ortho-ary

Full text of DOI:10.1021/jo401716p

Article
pubs.acs.org/joc
Palladium(II)-Catalyzed Ortho-Arylation of Benzylic Phosphonic
Monoesters Using Potassium Aryltrifluoroborates
Xiangjian Meng and Sunggak Kim*
Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University,
Singapore 637371, Singapore
S
* Supporting Information
ABSTRACT: The new monophosphonic acid directing group
was successfully utilized in the Pd (II)-catalyzed ortho-
arylation of benzylic phosphonic monoesters using potassium
aryltrifluoroborates. A wide range of benzylic phosphonic
monoesters underwent clean ortho-arylation in high yields, and excellent functional group tolerance was also observed.
Scheme 1. Reaction of 1a and 1b with Ph2IOTf
INTRODUCTION
■
Organophosphonates have attracted considerable attention due
to their wide applications in organic chemistry, medicinal
chemistry, and material science.1 A particularly important class
of organophosphonates is benzylic phosphonates, which are
common structural motifs in biological chemistry2 and have
already become a powerful tool in construction of alkene
derivatives via the Horner−Wadsworth−Emmons reaction in
organic synthesis.3
AgOAc oxidant (3 equiv) in refluxing dioxane. As shown in
Table 1, phenylation occurred to some extent using reagent I
(entries 1 and 2), but reagent II, III, and IV were totally
ineffective and no reaction occurred (entries 3, 4, and 5).
Inspired by recent reports on the C−H arylation of
phenylacetic acids,9 we next used potassium aryltrifluoroborate
salts as a coupling partner but the initial result was not very
promising.12,13 The ortho-arylation of 4 using PhBF3K in
refluxing tert-amyl alcohol did not go to completion, yielding a
70:30 mixture of 4 and 5 (entry 6). The reaction was
accelerated significantly in the presence of an amino acid ligand,
but the nature of amino acid ligands did not influence the reac-
tion greatly. Furthermore, poor mono-substitutions together
with some remaining starting materials were noted (entries
7−10). Among the bases tested in this study, KHF2 gave the
best result, although the starting material was not consumed
completely (entries 11−13).
To search for the optimum condition, when 1b was treated
with PhBF3K using 10 mol % Pd(OAc)2 catalyst, 20 mol %
Ac-Val-OH ligand, and AgOAc oxidant in refluxing tert-butyl
alcohol for 24 h, a 63:32 mixture of 2b and 1b was obtained
(entry 1, Table 2). Ag2O oxidant was equally effective (entry 2),
and Boc-Val-OH ligand was slightly less effective (entry 3).
After many futile experiments to search for the completion of
the reaction, the effectiveness of other Pd(II) catalysts was
investigated. PdCl2 was inferior to Pd(OAc)2 (entry 4),
whereas PdCl2(PPh3)2 was equally effective as Pd(OAc)2 but
was not good enough to be used (entry 5). Gratifyingly,
During recent decades, significant progress in transition
metal-catalyzed C−H bond activation methodology has been
made for ortho-functionalizations of arenes.4 In particular, a
directing group-based C−H activation approach has flourished
in the construction of new C−C and C−heteroatom bonds.
Among various ortho-directing groups, carbonyl derivatives are
widely utilized along with N-derived groups.5,6 Despite many
available ortho-directing groups, the development of new,
efficient directing groups still constitutes an important synthetic
challenge.
In connection with our interest in C−H functionalization of
arenes, we have reported Pd(II)-catalyzed ortho-alkenylation
using new monophosphoric acid directing groups.7,8 As
extension of our work, we have investigated ortho-arylation
of benzylic phosphonate monoesters. In analogous studies, Yu
reported the Pd(II)-catalyzed ortho-arylation of benzylic acids
using arylboron reagents and also found remarkable beneficial
effects of amino acid ligands.9
RESULTS AND DISCUSSION
■
Recently, we have succeeded in achieving Pd(II)-catalyzed
ortho-arylation of 1a using diaryliododium triflates.10a To
achieve arylation of aryl benzylic phosphonates, when the same
reaction was attempted using 1b, somewhat surprisingly, O-
phenylation occurred to some extent without the formation of
2b (Scheme 1). O-Arylation of phenols using diaryliodonium
triflates was recently noted.11 The reaction was sensitive to the
oxidant used, and the desired product 2b was not formed in any
cases. To achieve ortho-arylation, we next screened several
organoboron reagents using 10 mol % Pd(OAc)2 catalyst and
Received: August 6, 2013
Published: October 4, 2013
© 2013 American Chemical Society
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Table 1. Optimization of Reaction Conditions
a
b
c
entry
boron reagent
ligand (20 mol %)
additive (1 equiv)
co-oxidant (2 equiv)
solvent
yield (%) (5:6:4)
1
I
−
−
−
−
−
−
−
−
DMF
20:0:80
30:0:70
0:0:100
0:0:100
0:0:100
2
I
K2HPO4
K2HPO4
K2HPO4
−
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
K2HPO4
Li2CO3
KHF2
BQ
BQ
BQ
−
dioxane
dioxane
dioxane
dioxane
tamylOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
3
II
III
IV
V
V
V
V
V
V
V
V
4
5
d
6
BQ
30:0:70
7
Boc-Ala-OH
Boc-Val-OH
Boc-Ile-OH·0.5 H2O
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
−
−
−
35:15:50
42:29:29
50:23:27
43:32:25
39:13:48
38:20:42
57:25:18
8
9
10
11
12
13
−
−
−
a
Structures of boron reagents:
b
c
d
The yield and ratio was determined by 1H NMR analysis. The mixture was converted to its methyl ester with diazomethane. The reaction was
carried out using Ag2CO3 (2 equiv) at 130 °C for 24 h.
Table 2. Optimization of Reaction Conditions
After establishing the optimal reaction conditions, we applied
this new arylation protocol to a series of benzylic phosphonic
monoesters as shown in Table 3. For facile purification, the
crude arylated products were methylated using diazomethane
to furnish the corresponding methyl esters 8. The reaction was
not influenced significantly by either electron-donating or
electron-withdrawing groups on the arenes. For instance,
substrates bearing electron-donating groups (Me and OMe)
were converted to the arylated products in good to excellent
yields (8a−e). However, the position of the substituents on the
arenes could not be ignored on the transformation. Undoubtly,
monoarylated products were obtained if the ortho position was
blocked (8a, 8d). In the case of meta-substituted phosphonic
acids, the reaction occurred at the less sterically hindered
position to give the only monoarylated products (8b, 8e).
When the reaction was carried out with methyl hydrogen
phenylphosphonate (7c) using 1.1 equiv of PhBF3K, a 51:15
mixture of 8c and 9c along with recovery of 7c (23%). For
para-substituted substrate 7i, a similar result was obtained. The
o- and m-chloro-substituted substrates underwent ortho-
phenylation cleanly, giving the desired products (8f, 8g, 8h)
in high yields, whereas the fluoro-substituted substrates were
influenced to some extent by the ortho- and meta-substitution.
The meta-substituted substrates worked well to afford the
products in excellent yields (8k, 8l), while the ortho-substituted
substrate slowed down the reaction, yielding 8j in 71% yield
together with recovery of starting material 7j (25%). Notably,
phosphonic monoester 7m bearing a strong electron-withdrawing
CF3 group underwent clean phenylation to give 8m in
92% yield. Naphthyl derivatives also worked well to give the
corresponding arylated products 8n and 8o in 87% and 76%,
respectively. As shown in Scheme 2, the phenylation of a
secondary and a tertiary benzylic substrate was briefly examined
and two noteworthy features were found. First, secondary
a
ligand
oxidant
(2 equiv)
yield (%)
(2b:1b)
entry cat. (10 mol %) (20 mol %)
solvent
1
Pd(OAc)2
Ac-Val-OH
Ac-Val-OH
Boc-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
−
Boc-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
Ac-Val-OH
AgOAc
Ag2O
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
tBuOH
DMSO
toluene
dioxane
DMF
63:32
65:26
49:43
11:76
62:27
2
Pd(OAc)2
3
Pd(OAc)2
Ag2O
4
PdCl2
Ag2O
5
PdCl2(PPh3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
PdCl2(PEt3)2
Ag2O
b
6
Ag2O
85:8
7
Ag2O
62:28
60:34
23:70
10:81
0:100
0:100
12:80
35:21
36:17
8
Ag2O
9
AgOAc
Ag2CO3
Na2S2O8
Cu(OAc)2
Ag2O
10
11
12
13
14
15
16
Ag2O
Ag2O
Ag2O
1
62:30
b
a
The yield and ratio was determined by H NMR analysis. 2b was
converted to its methyl ester 2c with diazomethane.
PdCl2(PEt3)2 catalyst was found to be most effective for
arylation of 1b under the same conditions (entry 6).14 Among
the oxidants tested in this study, Na2S2O8 and Cu(OAc)2 were
totally ineffective (entries 11 and 12) and Ag2O gave the best
results (entry 6). Furthermore, the reaction was sensitive to
solvent, and tert-butyl alcohol was found to be the superior
solvent (entries 13−16).
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Table 3. Substrate Scope of Benzyl Phosphoric Acids
Table 4. Substrate Scope of Potassium Aryltrifluoroborates
a
The reaction was carried out with Ac‑Val‑OH (20 mol %), Ag2O
(2 equiv), and KHF2 (1 equiv) in t‑BuOH at 110 °C for 24 h.
b
c
Isolated yield. Isolated yield of the recovered 7b.
a
The reaction was carried out with Ac-Val-OH (20 mol %), Ag2O
(2 equiv), KHF2 (1 equiv) in t-BuOH at 110 °C for 24 h.
the meta-substituents. Consistent with this observation, the
ortho-substituted aryltrifluoroborates could not be used as the
coupling partners. Thus, 12j and 12k were not obtained,
although 12l was isolated only in 13% yield. Furthermore,
potassium vinyl and n-butyl trifluoroborate failed to undergo
ortho-alkenylation and alkylation under the standard con-
ditions.
b
c
d
Isolated yield. 1.1 equiv of PhBF3K was used. The isolated yield of
the recovered starting material.
Scheme 2. Ortho-Phenylation of 10 with PhBF3K
To demonstrate further transformations of the ortho-arylated
products using the Horner−Wadsworth−Emmons reaction
(Scheme 3),3,15 8b was treated with benzaldehyde using
Scheme 3. Horner−Wadworth−Emmons Reaction of 8b
substrate 10a underwent smooth phenylation to give 11a in
88% yield but tertiary substrate 10c failed probably due to steric
hindrance. Second, selective monophenylation at the ortho-
position was achieved with 10b.
To further determine the scope of the method, structurally
different potassium aryltrifluoroborates were utilized under the
standard conditions (Table 4). Potassium aryltrifluoroborates
containing electron-withdrawing groups (F, Cl, CN) reacted
with 7b to afford the corresponding ortho-arylated products in
high yields (12a−d). In the case of the strong electron-
withdrawing CF3 group, the arylation slowed, yielding 12e
(73%) along with recovery of 7b (20%). This catalytic system
also effectively promoted the cross-coupling of 7b with boron
reagents bearing electron-donating groups (OMe and Me) to
provide the desired products in moderate to excellent yields.
Although potassium 4-methoxyphenyltrifluoroborate worked as
an excellent coupling partner as shown in 12f, the meta-
substituted boron reagents slowed the reaction considerably
(12g and 12h), probably arising from the steric hindrance of
sodium hydroxide and n-tetrabutylammonium bromide in
toluene at 35 °C for 15 h to give the desired product 13a
in 81% yield. A similar result was also obtained with
p-chlorobenzaldehyde.
On the basis of the previous studies of Pd(II)-catalyzed C−H
arylation reactions,9 we envisioned that the process might be
promoted by the Pd(II) species I as shown in Scheme 4, which
activated C−H bond to generate the palladacyclic complex II
with the assistance of phosphonic directing group. Subsequent
transmetalation and reductive elimination would afford the
ortho-arylated product along with liberation of Pd(0).
Reoxidation with silver(I) oxide regenerates the active Pd(II)
species I.
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2358, 1597, 1490, 1267, 1031, 860, 734.; HRMS (ESI) m/z calcd for
C11H17O5PCl (M + H)+ 295.0502, found 295.0504.
Scheme 4. A Plausible Mechanism
Dimethyl 3-(Trifluoromethyl)benzylphosphonate. Yield:
180.0 mg, 67%, colorless liquid; 1H NMR (400 MHz, CDCl3) δ
7.54−7.47 (m, 3H), 7.45 (t, J = 7.9 Hz, 1H), 3.71 (s, 3H), 3.68
(s, 3H), 3.24 (s, 1H), 3.19 (s, 1H).; 13C NMR (101 MHz, CDCl3) δ
133.1 (d, J = 6.2 Hz), 132.5 (d, J = 9.0 Hz), 131.0 (dd, J = 33.0, 2.2
Hz), 129.1 (d, J = 3.0 Hz), 126.4 (dd, J = 6.9, 3.7 Hz), 124.0 (q, J =
270.6 Hz), 123.9 (t, J = 3.7 Hz), 52.9 (d, J = 6.8 Hz), 32.8 (d, J = 139.0
Hz).; 31P NMR (162 MHz, CDCl3) δ 27.6.; 19F NMR (377 MHz,
CDCl3) δ −62.7.; IR (film) ν 2956, 1450, 1330, 1126, 1033, 889, 702.;
HRMS (ESI) m/z calcd for C10H13O3F3P (M + H)+ 269.0554, found
269.0554.
Dimethyl 1-o-Tolylethylphosphonate. Yield: 171.0 mg, 75%,
1
colorless liquid; H NMR (400 MHz, CDCl3) δ 7.48−7.46 (m, 1H),
7.23−7.09 (m, 3H), 3.68 (d, J = 10.6 Hz, 3H), 3.50−3.48 (m, 1H),
3.48 (d, J = 10.5 Hz, 3H), 2.37 (d, J = 1.1 Hz, 3H), 1.54 (dd, J = 18.7,
7.3 Hz, 3H).; 13C NMR (101 MHz, CDCl3) δ 136.3 (d, J = 6.0 Hz),
136.1 (d, J = 7.0 Hz), 130.4 (d, J = 2.4 Hz), 127.9 (d, J = 4.8 Hz),
126.9 (d, J = 3.2 Hz), 126.3 (d, J = 3.1 Hz), 53.3 (d, J = 7.1 Hz), 52.8
(d, J = 7.4 Hz), 33.1 (d, J = 138.0 Hz), 19.9, 15.8 (d, J = 5.2 Hz).; 31P
NMR (162 MHz, CDCl3) δ 32.9.; IR (film) ν 3051, 2953, 2357, 1462,
1265, 1037, 827, 732.; HRMS (ESI) m/z calcd for C11H18O3P (M +
H)+ 229.0994, found 229.0995.
Dimethyl 1-Phenylethylphosphonate. Yield: 154.1 mg, 72%,
colorless liquid; H NMR (400 MHz, CDCl3) δ 7.29−7.23 (m, 4H),
CONCLUSION
1
■
We have developed a new, efficient method for direct ortho-
arylation of benzylic phosphonic monoesters using potassium
aryltrifluoroborates via Pd(II)-catalyzed C−H activation. The
present arylation approach is not influenced significantly by the
electronic properties of two coupling partners and would be
very useful to prepare various biaryl compounds through
further functionalizations using the Horner−Wadsworth−
Emmons reactions.
7.19 (dd, J = 4.7, 2.2 Hz, 1H), 3.62 (d, J = 10.6 Hz, 3H), 3.46 (d, J =
10.5 Hz, 3H), 3.14 (dd, J = 22.7, 7.4 Hz, 1H), 1.51 (dd, J = 18.5,
7.4 Hz, 3H).; 13C NMR (101 MHz, CDCl3) δ 137.68 (d, J = 6.9 Hz),
128.60 (d, J = 6.7 Hz), 128.54 (d, J = 2.7 Hz), 127.18 (d, J = 3.2 Hz),
53.04 (dd, J = 48.9, 7.1 Hz), 38.08 (d, J = 137.8 Hz), 15.54 (d, J = 5.1
Hz).; 31P NMR (162 MHz, CDCl3) δ 32.1.; IR (film) ν 2954, 1633,
1494, 1454, 1219, 1029,823, 763, 700.; HRMS (ESI) m/z calcd for
C10H16O3P (M + H)+ 215.0837, found 215.0842.
Dimethyl 2-Phenylpropan-2-ylphosphonate. Yield: 157.3 mg,
1
69%, colorless liquid; H NMR (400 MHz, CDCl3) δ 7.56−7.54 (m,
EXPERIMENTAL SECTION
2H), 7.35 (t, J = 7.7 Hz, 2H), 7.26−7.25 (m, 1H), 3.57 (s, 3H), 3.55
(s, 3H), 1.61 (s, 3H), 1.60 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ
141.3 (d, J = 5.0 Hz), 128.1 (d, J = 2.7 Hz), 127.6 (d, J = 5.3 Hz),
126.8 (d, J = 3.2 Hz), 53.4 (d, J = 7.4 Hz), 39.3 (d, J = 136.4 Hz), 23.9
(d, J = 4.1 Hz).; 31P NMR (162 MHz, CDCl3) δ 34.6.; IR (film) ν
2955, 1645, 1497, 1231, 1053, 1028, 806, 698.; HRMS (ESI) m/z
calcd for C11H18O3P (M + H)+ 229.0994, found 229.0992.
■
General Methods. A variety of chemical reagents were
commercially purchased and used without further purification.
Analytical TLC was carried out on precoated plates and visualized
with UV light or stained with potassium permanganate. H and 13C
1
NMR spectra were measured at 298 K on 400 Fourier transform NMR
spectrometer. Chemical shifts were reported in δ (ppm), relative to the
internal standard of TMS. The signals observed were described as
follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet).
The number of protons (n) for a given resonance was indicated as nH.
Coupling constants are reported as J value in hertz. 13C NMR is
reported as δ (ppm) downfield from TMS and relative to the signal of
chloroform-d (δ 77.00, triplet). Mass spectrometry was obtained using
a Q-tof high resolution mass spectrometer.
General Procedure for Preparation of Methyl Hydrogen
Benzylic Phosphonate 7.2a To a solution of dimethyl benzylic
phosphonate (0.5 mmol) in SOCl2 (0.5 mL) was added a catalytic
amount of DMF (3.7 mg, 0.05 mmol) at room temperature. The
reaction mixture was allowed to stir at reflux for 3 h. Excess SOCl2 was
removed, and the residue was diluted with dichloromethane (10 mL).
Cool water (1.0 mL) was then added to the solution at 0 °C, and the
mixture was stirred for 10 min. The organic layer was separated and
washed with brine, dried over MgSO4, filtered, and concentrated in
vacuo. The resulting residue was purified by flash chromatography on
silica (dichloromethane/methanol = 20:1) to afford methyl hydrogen
benzylic phosphonate 7. The spectral data of 1b, 4, 7a−g, 7i−l, 7n, 7o
have been reported previously.7a
Methyl Hydrogen 2-Chloro-3,4-dimethoxybenzylphospho-
nate (7h). Yield: 122.0 mg, 83%, colorless liquid; 1H NMR (400 MHz,
CDCl3) δ 7.14−7.06 (m, 1H), 6.77 (d, J = 8.6 Hz, 1H), 3.88−3.77 (m,
6H), 3.63−3.58 (m, 3H), 3.28 (s, 1H), 3.23 (s, 1H).; 13C NMR (101
MHz, CDCl3) δ 152.7 (d, J = 2.9 Hz), 145.6, 129.1 (d, J = 7.9 Hz),
126.1 (d, J = 5.6 Hz), 122.5 (d, J = 9.0 Hz), 110.6 (d, J = 3.4 Hz), 60.5,
56.0, 52.2 (d, J = 6.8 Hz), 29.9 (d, J = 142.0 Hz).; 31P NMR (162
MHz, CDCl3) δ 29.9.; IR (film) ν 2852, 2358, 1635, 1489, 1043, 989.;
HRMS (ESI) m/z calcd for C10H15O5PCl (M + H)+ 281.0346, found
281.0343.
General Procedure for Preparation of Dimethyl Benzylic
Phosphonates.16 To a solution of benzylic alcohol (1.0 mmol) in
anhydrous toluene (10 mL) were added ZnI2 (1.5 mmol) and
P(OMe)3 (2.0 mmol) under nitrogen. The reaction mixture was
heated to 110 °C for 15 h under nitrogen. After being cooled to room
temperature, the solvent was removed in vacuo. The residue was
diluted with diethyl ether (20 mL), washed with 2 N NaOH (2 ×
5 mL) and brine, and dried over anhydrous Na2SO4. After removal of
the solvent, the residue was purified via flash column chromatography
on silica gel (hexane/ethyl acetate = 2:1) to afford dimethyl benzylic
phosphonate. Spectral data of dimethyl benzylic phosphonates of 1b,
4, 7a−g, 7i−l, 7n, 7o are reported previously.7a
Dimethyl 2-Chloro-3,4-dimethoxybenzylphosphonate.
Yield: 229.4 mg, 78%, colorless liquid; H NMR (400 MHz, CDCl3)
1
δ 7.12 (dd, J = 8.6, 3.0 Hz, 1H), 6.79 (d, J = 8.6 Hz, 1H), 3.84 (d, J =
2.6 Hz, 6H), 3.69 (s, 3H), 3.66 (s, 3H), 3.33 (s, 1H), 3.28 (s, 1H).;
13C NMR (101 MHz, CDCl3) δ 152.8 (d, J = 3.5 Hz), 145.7 (d, J =
3.0 Hz), 128.9 (d, J = 8.0 Hz), 126.1 (d, J = 5.5 Hz), 122.4 (d, J = 9.1
Hz), 110.8 (d, J = 3.4 Hz), 60.6, 56.1, 52.8 (d, J = 6.8 Hz), 29.4 (d, J =
140.3 Hz).; 31P NMR (162 MHz, CDCl3) δ 28.2.; IR (film) ν 2953,
Methyl Hydrogen 3-(Trifluoromethyl)benzylphosphonate
(7m). Yield: 108.6 mg, 81%, yellow oil; 1H NMR (400 MHz,
CDCl3) δ 8.43 (br, 1H), 7.51 (d, J = 11.3 Hz, 2H), 7.47−7.38
(m, 2H), 3.55 (d, J = 11.2 Hz, 3H), 3.13 (s, 1H), 3.08 (s, 1H).; 13C NMR
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(101 MHz, CDCl3) δ 133.3 (d, J = 6.3 Hz), 132.4 (d, J = 9.2 Hz),
130.9 (dd, J = 32.3, 3.1 Hz), 128.9 (d, J = 3.0 Hz), 126.5 (dd, J =
6.7, 3.7 Hz), 123.9 (q, J = 272.7 Hz), 123.8 (t, J = 3.6 Hz), 52.0 (d, J =
7.1 Hz), 33.1 (d, J = 141.2 Hz).; IR (film) ν 2987, 1450, 1330, 1167,
1126, 1049, 740, 702.; 31P NMR (162 MHz, CDCl3) δ 29.1.; 19F NMR
(377 MHz, CDCl3) δ −62.7.; HRMS (ESI) m/z calcd for C9H11O3PF3
(M + H)+ 255.0398, found 255.0397.
Methyl Hydrogen 1-o-Tolylethylphosphonate (10a). Yield:
90.1 mg, 79%, yellow oil; 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J =
7.5 Hz, 1H), 7.22−7.08 (m, 3H), 3.54−3.47 (m, 3H), 3.47−3.36 (m,
1H), 2.36 (s, 3H), 1.52 (dd, J = 18.7, 7.3 Hz, 3H).; 13C NMR (101
MHz, CDCl3) δ 136.6 (d, J = 8.1 Hz), 136.2 (d, J = 6.7 Hz), 130.3 (d,
J = 2.5 Hz), 127.8 (d, J = 4.8 Hz), 126.8 (d, J = 3.2 Hz), 126.2 (d, J =
3.2 Hz), 51.9 (d, J = 7.5 Hz), 32.9 (d, J = 140.0 Hz), 19.9, 15.5 (d, J =
5.1 Hz).; 31P NMR (162 MHz, CDCl3) δ 34.2.; IR (film) ν 3003,
2250, 1705, 1361, 1223, 1051, 918, 732.; HRMS (ESI) m/z calcd for
C10H16O3P (M + H)+ 215.0837, found 215.0836.
over anhydrous MgSO4 and concentrated in vacuo to yield the crude
product, which was subjected to silica gel column chromatography
(dichloromethane/acetone = 10:1) to get the acid. The crude acid was
dissolved in diethyl ether and treated with an excess amount of CH2N2
in diethyl ether at room temperature for 0.5 h. Diethyl ether was
evaporated under reduced pressure and the crude product was purified
by passing through silica gel flash column (dichloromethane/acetone =
20:1) to afford 8a (27.6 mg, 91%).
Dimethyl (3-Methylbiphenyl-2-yl)methylphosphonate (2c).
1
Yield: 23.6 mg, 81%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.46−7.38 (m, 2H), 7.34 (dd, J = 7.2, 5.5 Hz, 3H), 7.19 (dd, J = 4.0,
2.7 Hz, 2H), 7.08−7.05 (m, 1H), 3.42 (s, 3H), 3.40 (s, 3H), 3.36 (s,
1H), 3.31 (s, 1H), 2.51 (d, J = 1.5 Hz, 3H).; 13C NMR (101 MHz,
CDCl3) δ 143.3 (d, J = 6.4 Hz), 142.1, 138.1 (d, J = 5.5 Hz), 129.8 (d,
J = 3.8 Hz), 129.6, 128.4 (d, J = 3.6 Hz), 128.1, 127.8 (d, J = 3.1 Hz),
127.0 (s), 126.7 (d, J = 4.1 Hz), 52.3 (d, J = 6.9 Hz), 27.4 (d, J = 137.5
Hz), 20.9 (d, J = 1.4 Hz).; 31P NMR (162 MHz, CDCl3) δ 29.0.; IR
(film) ν 2953, 1462, 1252, 1055, 1029, 888, 839,704.; HRMS (ESI)
m/z calcd for C16H20O3P (M + H)+ 291.1150, found 291.1148.
Dimethyl (3,5-Dimethylbiphenyl-2-yl)methylphosphonate
(8a). Yield: 27.6 mg, 91%; yellow liquid; 1H NMR (400 MHz,
CDCl3) δ 7.41 (dd, J = 10.2, 4.4 Hz, 2H), 7.32 (dd, J = 7.1, 5.2 Hz,
3H), 7.02 (s, 1H), 6.89 (s, 1H), 3.42 (s, 3H), 3.39 (s, 3H), 3.32 (s,
1H), 3.26 (s, 1H), 2.46 (d, J = 1.4 Hz, 3H), 2.30 (d, J = 2.5 Hz, 3H).;
13C NMR (101 MHz, CDCl3) δ 143.1 (d, J = 6.3 Hz), 142.2, 137.9 (d,
J = 5.4 Hz), 136.2 (d, J = 4.2 Hz), 130.7 (d, J = 3.8 Hz), 129.5, 129.2
(d, J = 3.6 Hz), 128.1, 126.9, 124.5 (d, J = 10.0 Hz), 52.3 (d, J =
6.9 Hz), 27.0 (d, J = 137.8 Hz), 20.8 (d, J = 5.7 Hz).; 31P NMR (162
MHz, CDCl3) δ 29.3.; IR (film) ν 2953, 1472, 1251, 1055, 1029, 819,
779, 704.; HRMS (ESI) m/z calcd for C17H22O3P (M + H)+ 305.1307,
found 305.1308.
Methyl Hydrogen 1-Phenylethylphosphonate (10b). Yield:
1
73.0 mg, 73%, colorless liquid; H NMR (400 MHz, CDCl3) δ 11.02
(br, 1H), 7.34−7.25 (m, 4H), 7.25−7.17 (m, 1H), 3.48 (d, J = 10.8
Hz, 3H), 3.12 (dd, J = 23.2, 7.4 Hz, 1H), 1.52 (dd, J = 18.7, 7.5 Hz,
3H).; 13C NMR (101 MHz, CDCl3) δ 137.8 (d, J = 7.1 Hz), 128.7 (d,
J = 6.5 Hz), 128.4 (d, J = 2.6 Hz), 127.0 (d, J = 3.2 Hz), 52.0 (d, J =
7.4 Hz), 37.9 (d, J = 140.1 Hz), 15.2 (d, J = 5.0 Hz). 31P NMR (162
MHz, CDCl3) δ 32.7.; IR (film) ν 2953, 2850, 1602, 1494, 1454, 821,
783, 765, 732, 698.; HRMS (ESI) m/z calcd for C9H14O3P (M + H)+
201.0681, found 201.0688.
Methyl Hydrogen 2-Phenylpropan-2-ylphosphonate (10c).
1
Yield: 75.3 mg, 66%, yellow oil; H NMR (400 MHz, CDCl3) δ 9.03
(br, 1H), 7.43 (d, J = 1.7 Hz, 1H), 7.37 (ddd, J = 7.1, 3.7, 1.9 Hz, 1H),
7.23−7.13 (m, 2H), 3.59 (d, J = 11.2 Hz, 3H), 3.06 (s, 1H), 3.01
(s, 1H).; 13C NMR (101 MHz, CDCl3) δ 141.3, 128.0, 127.7 (d, J =
4.3 Hz), 126.6, 52.2 (d, J = 7.2 Hz), 38.5 (d, J = 140.1 Hz), 23.6.;
31P NMR (162 MHz, CDCl3) δ 35.7.; IR (film) ν 3053, 2985, 1419,
1265, 1047, 976, 895, 739, 704.; HRMS (ESI) m/z calcd for
C10H16O3P (M + H)+ 215.0837, found 215.0841.
Pd(TFA)2-Catalyzed Reaction of Benzylic Phosphonic Mono-
ester 1b with Diphenyliododium Triflate. To a mixture of
benzylic phosphonic monoester 1b (20.0 mg, 0.1 mmol) and Ph2IOTf
(64.5 mg, 0.15 mmol) in 1,2-dichloroethane (1.5 mL) was added
Pd(TFA)2 (3.3 mg, 0.01 mmol). The reaction mixture was heated at
110 °C for 15 h in a sealed vial and then cooled to room temperature.
The crude mixture was filtered through a cotton plug to remove the
solid residues, and concentrated in vacuo. The crude mixture was
diluted with EtOAc (1 mL) and washed with aqueous Na2S2O3
(1 mL). The aqueous layer was further extracted with EtOAc
(3 mL × 3), and the combined organic layer was concentrated in
vacuo. The residue was purified by flash chromatography (dichloro-
methane/acetone = 20:1) to afford the O-phenylated product 3b
(6.9 mg, 25%) and the starting material 1b (12.0 mg, 60%).
Dimethyl (4-Methylbiphenyl-2-yl)methylphosphonate (8b).
1
Yield: 25.0 mg, 86%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.45−7.32 (m, 6H), 7.14 (t, J = 7.3 Hz, 2H), 3.59 (s, 3H), 3.56 (s,
3H), 3.21 (s, 1H), 3.15 (s, 1H), 2.39 (s, 3H).; 13C NMR (101 MHz,
CDCl3) δ 141.1, 139.8 (d, J = 8.1 Hz), 137.2 (d, J = 3.2 Hz), 131.1 (d,
J = 4.6 Hz), 130.4 (d, J = 2.7 Hz), 129.6, 128.2, 127.8 (d, J = 3.3 Hz),
127.0, 52.6 (d, J = 6.8 Hz), 29.3 (d, J = 138.1 Hz), 21.1.; IR (film) ν
2954, 1458, 1257, 1057, 1031, 867, 761, 704.; 31P NMR (162 MHz,
CDCl3) δ 29.5.; HRMS (ESI) m/z calcd for C16H20O3P (M + H)+
291.1150, found 291.1152.
Dimethyl Biphenyl-2-ylmethylphosphonate (8c). Yield: 14.1 mg,
51%; yellow liquid; 1H NMR (400 MHz, CDCl3) δ 7.57−7.52
(m, 1H), 7.46−7.40 (m, 2H), 7.40−7.35 (m, 3H), 7.33 (dd, J = 7.4,
2.1 Hz, 1H), 7.30 (dd, J = 5.4, 3.7 Hz, 1H), 7.25 (d, J = 5.4 Hz, 1H),
3.59 (s, 3H), 3.56 (s, 3H), 3.24 (s, 1H), 3.18 (s, 1H).; 13C NMR (101
MHz, CDCl3) δ 142.6 (d, J = 8.3 Hz), 141.1, 130.5 (d, J = 0.8 Hz),
130.5 (d, J = 3.3 Hz), 129.5, 128.7 (d, J = 8.7 Hz), 128.3, 127.5 (d, J =
3.4 Hz), 127.2, 127.0 (d, J = 3.5 Hz), 52.7 (d, J = 6.8 Hz), 29.4 (d, J =
138.3 Hz).; IR (film) ν 2953, 1481, 1254, 1051, 1030, 858, 746, 704.;
31P NMR (162 MHz, CDCl3) δ 29.3.; HRMS (ESI) m/z calcd for
C15H18O3P (M + H)+ 277.0994, found 277.0994.
Methyl Phenyl 2-Methylbenzylphosphonate (3b). Yield:
1
6.9 mg, 25%, colorless liquid; H NMR (400 MHz, CDCl3) δ 7.33−7.26
Dimethyl (3-Phenylbiphenyl-2-yl)methylphosphonate (9c).
(m, 3H), 7.21−7.11 (m, 4H), 7.10−7.06 (m, 2H), 3.69 (d, J = 11.0
Hz, 3H), 3.38 (s, 1H), 3.33 (d, J = 0.9 Hz, 1H), 2.39 (d, J = 1.7 Hz,
3H).; 13C NMR (101 MHz, CDCl3) δ 150.7 (d, J = 9.0 Hz), 137.1 (d,
J = 6.9 Hz), 130.7 (d, J = 5.7 Hz), 130.6 (d, J = 3.5 Hz), 129.2 (d, J =
9.7 Hz), 127.4 (d, J = 3.9 Hz), 126.2 (d, J = 3.6 Hz), 124.8, 120.3 (d,
J = 4.4 Hz), 53.4 (d, J = 7.3 Hz), 30.7 (d, J = 139.1 Hz), 20.0.; 31P
NMR (162 MHz, CDCl3) δ 24.7.; IR (film) ν 2958, 1591, 1489, 1261,
1205, 1041, 927, 802.; HRMS (ESI) m/z calcd for C15H18O3P
(M + H)+ 277.0994, found 277.0992.
1
Yield: 5.3 mg, 15%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.46−7.40 (m, 8H), 7.37−7.33 (m, 2H), 7.32−7.30 (m, 1H), 7.23 (d,
J = 7.6 Hz, 2H), 3.45 (s, 1H), 3.39 (s, 1H), 3.18 (s, 3H), 3.15 (s, 3H).;
13C NMR (101 MHz, CDCl3) δ 143.7 (d, J = 6.0 Hz), 142.1, 130.0
(d, J = 3.7 Hz), 129.7, 128.2, 127.1, 126.9 (d, J = 10.2 Hz), 126.6 (d,
J = 4.0 Hz), 51.8 (d, J = 6.8 Hz), 27.0 (d, J = 136.3 Hz).; 31P NMR
(162 MHz, CDCl3) δ 28.7.; IR (film) ν 2951, 1456, 1256, 1057, 1032,
868,761, 704.; HRMS (ESI) m/z calcd for C21H22O3P (M + H)+
353.1307, found 353.1304.
Dimethyl (3-Methoxybiphenyl-2-yl)methylphosphonate
(8d). Yield: 27.6 mg, 90%; yellow liquid; 1H NMR (400 MHz,
CDCl3) δ 7.44−7.38 (m, 2H), 7.37−7.32 (m, 3H), 7.239−7.239 (m,
1H), 6.88 (dd, J = 16.7, 8.0 Hz, 2H), 3.91 (s, 3H), 3.50 (s, 3H), 3.47
(s, 3H), 3.35 (s, 1H), 3.30 (s, 1H).; 13C NMR (101 MHz, CDCl3) δ
157.7 (d, J = 5.3 Hz), 144.0 (d, J = 6.7 Hz), 141.2, 129.5, 128.1, 127.5
(d, J = 3.9 Hz), 127.1, 122.9 (d, J = 3.5 Hz), 118.5 (d, J = 10.4 Hz),
109.4 (d, J = 3.4 Hz), 55.7, 52.2 (d, J = 6.5 Hz), 24.1 (d, J = 138.3 Hz).;
Typical Procedure for the Ortho-Arylation of Benzylic
Phosphonic Monoester 7a. To a mixture of benzylic phosphonic
monoester 7a (21.5 mg, 0.1 mmol) and PhBF3K (50.2 mg, 0.3 mmol)
in tert-butyl alcohol (1.5 mL) were added PdCl2(PEt3)2 (4.2 mg, 0.01
mmol), Ac-Val-OH (3.5 mg, 0.02 mmol), KHF2 (7.8 mg, 0.1 mmol),
and Ag2O (46.4 mg, 0.2 mmol). The reaction mixture was heated at
110 °C for 24 h in a sealed vial. After the reaction mixture was cooled
to 0 °C, EtOAc (10 mL) and 2.0 N HCl solution (1 mL) were added.
The organic layer was separated and washed with brine, it was dried
11251
dx.doi.org/10.1021/jo401716p | J. Org. Chem. 2013, 78, 11247−11254

The Journal of Organic Chemistry
Article
IR (film) ν 2953, 1573, 1470, 1260, 1032, 886, 764, 706.; 31P NMR
(162 MHz, CDCl3) δ 29.8.; HRMS (ESI) m/z calcd for C16H20O4P
(M + H)+ 307.1099, found 307.1092.
7.23−7.19 (m, 1H), 7.00 (dd, J = 16.4, 8.2 Hz, 2H), 3.48 (s, 3H), 3.45
(s, 3H), 3.25 (d, J = 2.3 Hz, 1H), 3.19 (d, J = 2.3 Hz, 1H).; 13C NMR
(101 MHz, CDCl3) δ 161.3(dd, J = 246.9, 5.9 Hz), 144.8 (d, J =
3.5 Hz), 140.0, 129.4, 128.3, 128.1 (dd, J = 9.3, 3.8 Hz), 127.5, 126.2
(t, J = 3.2 Hz), 117.5 (dd, J = 15.7, 10.1 Hz), 114.3 (dd, J = 22.8, 3.5
Hz), 52.5 (d, J = 6.4 Hz), 23.5 (dd, J = 139.4, 3.3 Hz).; 31P NMR (162
MHz, CDCl3) δ 27.8 (d, J = 3.6 Hz).; 19F NMR (376 MHz, CDCl3) δ
−113.3 (d, J = 3.7 Hz).; IR (film) ν 2953, 1636, 1464, 1265, 1032, 902,
736, 702.; HRMS (ESI) m/z calcd for C15H17O3PF (M + H)+
295.0899, found 295.0899.
Dimethyl (4-Methoxybiphenyl-2-yl)methylphosphonate
(8e). Yield: 26.1 mg, 85%; yellow liquid; 1H NMR (400 MHz,
CDCl3) δ 7.42 (d, J = 7.5 Hz, 2H), 7.34 (d, J = 7.3 Hz, 3H), 7.18 (d,
J = 8.4 Hz, 1H), 7.10 (s, 1H), 6.86 (d, J = 8.5 Hz, 1H), 3.85 (s, 3H),
3.60 (s, 3H), 3.58 (s, 3H), 3.21 (s, 1H), 3.16 (s, 1H).; 13C NMR (101
MHz, CDCl3) δ 158.8, 140.8, 135.2 (d, J = 8.3 Hz), 131.5 (d, J =
2.7 Hz), 129.9 (d, J = 8.8 Hz), 129.7, 128.3, 126.9, 115.5 (d, J = 4.8
Hz), 112.9 (d, J = 3.4 Hz), 55.4, 52.7 (d, J = 6.8 Hz), 29.6 (d, J = 138.1
Hz).; 31P NMR (162 MHz, CDCl3) δ 29.2.; IR (film) ν 2955, 1608,
1485, 1234, 1030, 712, 705.; HRMS (ESI) m/z calcd for C16H20O4P
(M + H)+ 307.1099, found 307.1097.
Dimethyl (4-Fluorobiphenyl-2-yl)methylphosphonate (8k).
1
Yield: 23.6 mg, 80%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.47−7.41 (m, 2H), 7.35 (dd, J = 12.8, 7.3 Hz, 3H), 7.23 (dd, J = 12.4,
5.4 Hz, 2H), 7.01 (d, J = 8.1 Hz, 1H), 3.63 (s, 3H), 3.60 (s, 3H), 3.20
(s, 1H), 3.14 (s, 1H).; 13C NMR (101 MHz, CDCl3) δ 161.9 (d, J =
242.4 Hz), 140.1, 138.7 (dd, J = 9.5, 4.8 Hz), 131.9 (dd, J = 8.2, 2.8
Hz), 131.0 (t, J = 8.4 Hz), 129.6, 128.4, 127.4, 117.0 (dd, J = 22.3, 4.8
Hz), 114.0 (dd, J = 21.1, 3.4 Hz), 52.7 (d, J = 6.7 Hz), 29.6 (d, J =
Dimethyl (3-Chlorobiphenyl-2-yl)methylphosphonate (8f).
1
Yield: 25.8 mg, 83%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.36 (t, J = 7.5 Hz, 3H), 7.30 (d, J = 7.2 Hz, 1H), 7.26 (d, J = 7.2 Hz,
2H), 7.15 (dd, J = 7.8, 2.4 Hz, 1H), 7.07 (d, J = 7.5 Hz, 1H), 3.45 (s,
1H), 3.43 (s, 3H), 3.40 (s, 3H), 3.41 (s, 1H),; 13C NMR (101 MHz,
CDCl3) δ 144.8 (d, J = 6.1 Hz), 140.9, 135.3 (d, J = 6.5 Hz), 129.4,
129.2 (d, J = 3.6 Hz), 128.9 (d, J = 3.6 Hz), 128.3, 127.7 (d, J = 3.9
Hz), 127.5, 52.4 (d, J = 6.7 Hz), 28.1 (d, J = 138.3 Hz).; IR (film) ν
2953, 1562, 1452, 1265, 1031, 870, 793, 164, 704.; 31P NMR (162
MHz, CDCl3) δ 27.5.; HRMS (ESI) m/z calcd for C15H17O3PCl (M +
H)+ 311.0604, found 311.0608.
138.6 Hz).; 31P NMR (162 MHz, CDCl3) δ 28.5 (d, J = 2.1 Hz).; 19
F
NMR (376 MHz, CDCl3) δ −114.9 (d, J = 2.6 Hz).; IR (film) ν 2955,
1609, 1483, 1252, 1031, 956, 816, 708.; HRMS (ESI) m/z calcd for
C15H17O3PF (M + H)+ 295.0899, found 295.0898.
Dimethyl (4-Fluoro-5-methoxybiphenyl-2-yl)methylphos-
phonate (8l). Yield: 26.3 mg, 81%; yellow liquid; 1H NMR
(400 MHz, CDCl3) δ 7.43 (d, J = 7.4 Hz, 2H), 7.37 (dd, J = 9.1,
7.6 Hz, 3H), 7.25 (d, J = 7.4 Hz, 1H), 6.84 (d, J = 8.7 Hz, 1H), 3.87 (s,
3H), 3.63 (s, 3H), 3.60 (s, 3H), 3.11 (s, 1H), 3.05 (s, 1H).; 13C NMR
(101 MHz, CDCl3) δ 151.4 (dd, J = 246.1, 3.8 Hz), 146.2 (dd, J =
10.8, 3.3 Hz), 140.4, 139.4−13.0 (m), 129.5, 128.4, 127.5, 121.3 (dd,
J = 9.0, 6.8 Hz), 117.7 (dd, J = 19.1, 4.5 Hz), 115.4, 56.3, 52.7 (d, J =
6.8 Hz), 28.7 (d, J = 139.5 Hz).; 31P NMR (162 MHz, CDCl3) δ 28.9.;
19F NMR (376 MHz, CDCl3) δ −136.7 (d, J = 2.5 Hz).; IR (film)
Dimethyl (4-Chlorobiphenyl-2-yl)methylphosphonate (8g).
1
Yield: 25.5 mg, 82%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.51 (t, J = 2.4 Hz, 1H), 7.43 (dd, J = 7.9, 6.3 Hz, 2H), 7.36 (ddd, J =
8.3, 6.9, 1.5 Hz, 3H), 7.30−7.26 (m, 1H), 7.21−7.17 (m, 1H), 3.63 (s,
3H), 3.60 (s, 3H), 3.19 (s, 1H), 3.13 (s, 1H).; 13C NMR (101 MHz,
CDCl3) δ 141.1 (d, J = 8.2 Hz), 139.9, 133.3 (d, J = 4.0 Hz), 131.7 (d,
J = 2.8 Hz), 130.8 (d, J = 8.8 Hz), 130.2 (d, J = 4.9 Hz), 129.4, 128.4,
127.5, 127.2 (d, J = 3.5 Hz), 52.8 (d, J = 6.8 Hz), 29.4 (d, J = 138.7
Hz).; 31P NMR (162 MHz, CDCl3) δ 28.4.; IR (film) ν 2953, 1635,
1476, 1252, 1030, 888, 809, 704.; HRMS (ESI) m/z calcd for
C15H17O3PCl (M + H)+ 311.0604, found 311.0607.
ν 2955, 1636, 1516, 1232, 1034, 830, 704.; HRMS (ESI) m/z calcd for
C16H19O4P F (M + H)+ 325.1005, found 325.1010.
Dimethyl (4-(Trifluoromethyl)biphenyl-2-yl)methylphos-
phonate (8m). Yield: 31.7 mg, 92%; yellow liquid; 1H NMR
(400 MHz, CDCl3) δ 7.77 (s, 1H), 7.56 (d, J = 8.1 Hz, 1H), 7.49−
7.35 (m, 6H), 3.63 (s, 3H), 3.60 (s, 3H), 3.26 (s, 1H), 3.20 (s, 1H).;
13C NMR (101 MHz, CDCl3) δ 146.2 (d, J = 9.2 Hz), 139.8, 131.0
(d, J = 2.8 Hz), 130.1 (d, J = 8.8 Hz), 129.2, 128.5, 127.9, 127.5−127.0
(m), 123.7 (t, J = 3.6 Hz), 52.8 (d, J = 6.8 Hz), 29.5 (d, J = 138.8 Hz).;
31P NMR (162 MHz, CDCl3) δ 28.1.; 19F NMR (376 MHz, CDCl3) δ
Dimethyl (3-Chloro-4,5-dimethoxybiphenyl-2-yl)-
1
methylphosphonate (8h). Yield: 34.4 mg, 93%; yellow liquid; H
NMR (400 MHz, CDCl3) δ 7.48−7.40 (m, 2H), 7.39−7.31 (m, 3H),
7.26 (s, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 3.50 (s, 3H), 3.47 (s, 3H),
3.43 (s, 1H), 3.37 (s, 1H).; 13C NMR (101 MHz, CDCl3) δ 151.9 (d,
J = 3.8 Hz), 144.9, 141.1 (d, J = 1.6 Hz), 139.5 (d, J = 6.5 Hz), 129.8
(d, J = 6.0 Hz), 129.5, 128.3, 127.5, 120.9 (d, J = 10.5 Hz), 113.1 (d,
J = 3.6 Hz), 60.6, 56.1, 52.3 (d, J = 6.7 Hz), 27.9 (d, J = 139.5 Hz).;
31P NMR (162 MHz, CDCl3) δ 28.0.; IR (film) ν 2955, 1562, 1487,
1349, 1273, 1031, 886, 704.; HRMS (ESI) m/z calcd for C17H20O5PClNa
(M + Na)+ 393.0635, found 393.0630.
−62.5.; IR (film) ν 2954, 1636, 1332, 1126, 1032, 899, 704.; HRMS
(ESI) m/z calcd for C16H17O3PF3 (M + H)+ 345.0866, found
345.0867.
Dimethyl (2-Phenylnaphthalen-1-yl)methylphosphonate
(8n). Yield: 28.5 mg, 87%; yellow liquid; 1H NMR (400 MHz,
CDCl3) δ 8.03 (d, J = 3.6 Hz, 1H), 7.89−7.84 (m, 1H), 7.83−7.77 (m,
1H), 7.74 (s, 1H), 7.50−7.42 (m, 6H), 7.40 (dd, J = 6.1, 2.6 Hz, 1H),
3.58 (s, 3H), 3.55 (s, 3H), 3.39 (s, 1H), 3.33 (s, 1H).; 13C NMR (101
MHz, CDCl3) δ 141.1, 140.7 (d, J = 7.0 Hz), 132.6 (d, J = 3.5 Hz),
132.3 (d, J = 2.6 Hz), 129.7, 129.5 (d, J = 6.6 Hz), 129.3, 128.3, 127.5
(d, J = 7.4 Hz), 127.3, 127.1 (d, J = 8.9 Hz), 126.2, 52.7 (d, J = 6.8
Hz), 29.5 (d, J = 138.4 Hz).; 31P NMR (162 MHz, CDCl3) δ 29.2.; IR
(film) ν 2953, 1636, 1497, 1265, 1057, 1034, 815, 736, 702.; HRMS
(ESI) m/z calcd for C19H20O3P (M + H)+ 327.1150, found 327.1148.
Dimethyl (3-Phenylnaphthalen-2-yl)methylphosphonate
(8o). Yield: 24.8 mg, 76%, colorless liquid; 1H NMR (400 MHz,
CDCl3) δ 8.03 (d, J = 3.6 Hz, 1H), 7.90−7.84 (m, 1H), 7.82−7.79 (m,
1H), 7.74 (s, 1H), 7.50−7.44 (m, 6H), 7.41 (dd, J = 6.2, 2.5 Hz, 1H),
3.58 (s, 3H), 3.56 (s, 3H), 3.39 (s, 1H), 3.34 (s, 1H).; 13C NMR (101
MHz, CDCl3) δ 141.1, 140.7 (d, J = 7.1 Hz), 132.6 (d, J = 3.5 Hz),
132.3 (d, J = 2.5 Hz), 129.7, 129.5, 129.4, 129.3 (d, J = 2.2 Hz), 127.9
(d, J = 1.5 Hz), 127.5 (d, J = 1.2 Hz), 127.1, 127.0, 126.3, 126.2, 52.7
(d, J = 6.8 Hz), 29.5 (d, J = 138.5 Hz).; 31P NMR (162 MHz, CDCl3)
δ 29.1.; IR (film) ν 3055, 2953, 2237, 1409, 1246, 1031, 910, 731,
704.; HRMS (ESI) m/z calcd for C19H20O3P (M + H)+ 327.1150,
found 327.1143.
Dimethyl (5-Chlorobiphenyl-2-yl)methylphosphonate (8i).
1
Yield: 14.6 mg, 47%; yellow liquid; H NMR (400 MHz, CDCl3) δ
7.50−7.41 (m, 3H), 7.41−7.28 (m, 5H), 3.60 (s, 3H), 3.58 (s, 3H),
3.18 (s, 1H), 3.12 (s, 1H).; 13C NMR (101 MHz, CDCl3) δ 144.2 (d,
J = 8.3 Hz), 139.8, 132.7 (d, J = 4.2 Hz), 131.8 (d, J = 4.9 Hz), 130.3
(d, J = 2.9 Hz), 129.3, 128.4, 127.7, 127.6 (d, J = 3.4 Hz), 127.4 (d, J =
8.7 Hz), 52.7 (d, J = 6.7 Hz), 28.9 (d, J = 138.8 Hz).; 31P NMR (162
MHz, CDCl3) δ 28.7.; IR (film) ν 2955, 1636. 1472, 1250, 1057, 1031,
864, 806, 704.; HRMS (ESI) m/z calcd for C15H17O3PCl (M + H)+
311.0604, found 311.0600.
Dimethyl (5-Chloro-3-phenylbiphenyl-2-yl)methylphos-
phonate (9i). Yield: 4.6 mg, 12%; yellow liquid; 1H NMR (400
MHz, CDCl3) δ 7.41 (dd, J = 17.0, 7.0 Hz, 10H), 7.24 (d, J = 0.8 Hz,
2H), 3.38 (s, 1H), 3.32 (s, 1H), 3.19 (s, 3H), 3.16 (s, 3H).; 13C NMR
(101 MHz, CDCl3) δ 145.2 (d, J = 6.0 Hz), 140.8, 132.2 (d, J = 4.9
Hz), 129.7 (d, J = 3.8 Hz), 129.5, 128.3, 127.5, 125.8 (d, J = 10.3 Hz),
51.9 (d, J = 6.7 Hz), 26.6 (d, J = 136.8 Hz).; IR (film) ν 2954, 1636,
1570, 1423, 1265, 1058, 1034, 736, 702.; 31P NMR (162 MHz,
CDCl3) δ 28.1.; HRMS (ESI) m/z calcd for C21H21O3PCl (M + H)+
387.0917, found 387.0917.
Dimethyl (3-Fluorobiphenyl-2-yl)methylphosphonate (8j).
1
Yield: 21.0 mg, 71%; yellow liquid; H NMR (400 MHz, CDCl3) δ
Dimethyl 1-(3-Methylbiphenyl-2-yl)ethylphosphonate (11a).
1
7.37 (dd, J = 10.2, 4.2 Hz, 2H), 7.30 (ddd, J = 4.6, 3.3, 2.2 Hz, 3H),
Yield: 26.9 mg, 88%; yellow liquid; H NMR (400 MHz, CDCl3)
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δ 7.42−7.35 (m, 4H), 7.18−7.16 (m, 3H), 7.04−7.03 (m, 1H), 3.75−
3.63 (m, 1H), 3.55 (d, J = 10.7 Hz, 3H), 3.40 (d, J = 10.5 Hz, 3H),
2.70 (d, J = 1.2 Hz, 3H), 1.53 (dd, J = 18.4, 7.5 Hz, 3H).; 13C NMR
(101 MHz, CDCl3) δ 144.0 (d, J = 9.2 Hz), 142.7, 138.5 (d, J = 4.5
Hz), 133.8 (d, J = 4.7 Hz), 131.6 (d, J = 3.0 Hz), 129.8, 128.1 (d, J =
1.6 Hz), 127.9, 127.0, 126.4 (d, J = 2.8 Hz), 52.8 (d, J = 6.8 Hz), 52.2
(d, J = 7.2 Hz), 34.6 (d, J = 138.0 Hz), 21.5, 14.4 (d, J = 3.9 Hz).; 31P
NMR (162 MHz, CDCl3) δ 32.8.; IR (film) ν 2953, 1630, 1458, 1238,
1036, 820, 702.; HRMS (ESI) m/z calcd for C17H22O3P (M + H)+
305.1307, found 305.1309.
Hz, 2H), 7.35 (s, 1H), 7.13 (s, 2H), 3.63 (s, 3H), 3.60 (s, 3H), 3.14 (s,
1H), 3.08 (s, 1H), 2.40 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ
144.8, 138.4 (d, J = 8.1 Hz), 138.0 (d, J = 3.4 Hz), 131.3 (d, J = 5.0
Hz), 130.2 (d, J = 2.5 Hz), 130.0, 125.2 (d, J = 3.8 Hz), 52.7 (d, J = 6.8
Hz), 29.5 (d, J = 138.8 Hz), 21.2.; 31P NMR (162 MHz, CDCl3) δ
29.0.; 19F NMR (377 MHz, CDCl3) δ −62.4.; IR (film) ν 2955, 1635,
1618, 1325, 1166, 1124, 1031, 817, 736.; HRMS (ESI) m/z calcd for
C17H19O3PF3 (M + H)+ 359.1024, found 359.1021.
Dimethyl (4′-Methoxy-4-methylbiphenyl-2-yl)methylphos-
1
phonate (12f). Yield: 29.5 mg, 92%; yellow liquid; H NMR (400
MHz, CDCl3) δ 7.33 (s, 1H), 7.30−7.24 (m, 2H), 7.12 (t, J = 8.3 Hz,
2H), 6.97−6.93 (m, 2H), 3.85 (s, 3H), 3.61 (s, 3H), 3.58 (s, 3H), 3.20
(s, 1H), 3.15 (s, 1H), 2.38 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ
158.7, 139.5, 136.9 (d, J = 3.4 Hz), 133.5, 131.0 (d, J = 4.9 Hz), 130.6,
130.5 (d, J = 2.8 Hz), 128.6 (d, J = 8.7 Hz), 127.8 (d, J = 3.5 Hz),
113.7, 55.3, 52.7 (d, J = 6.8 Hz), 29.3 (d, J = 138.2 Hz), 21.1.; 31P
NMR (162 MHz, CDCl3) δ 29.6.; IR (film) ν 2953, 1610, 1493, 1246,
1057, 1034, 812, 735.; HRMS (ESI) m/z calcd for C17H22O4P
(M + H)+ 321.1256, found 321.1259.
Dimethyl 1-(Biphenyl-2-yl)ethylphosphonate (11b). Yield:
1
23.8 mg, 82%, colorless liquid; H NMR (400 MHz, CDCl3) δ 7.71
(d, J = 7.8 Hz, 1H), 7.45−7.28 (m, 7H), 7.23 (d, J = 7.6 Hz, 1H), 3.62
(d, J = 10.6 Hz, 3H), 3.50 (t, J = 8.3 Hz, 3H), 3.55−3.39 (m, 1H), 1.49
(dd, J = 18.7, 7.3 Hz, 3H).; 13C NMR (101 MHz, CDCl3) δ 142.2 (d,
J = 9.7 Hz), 141.2, 135.7 (d, J = 5.4 Hz), 130.3 (d, J = 2.0 Hz), 129.3,
128.3, 128.4 (d, J = 4.5 Hz), 128.3, 127.7 (d, J = 2.9 Hz), 126.8 (d, J =
2.7 Hz), 52.9 (dd, J = 60.5, 7.1 Hz), 33.3 (d, J = 138.8 Hz), 17.2 (d, J =
4.8 Hz).; 31P NMR (162 MHz, CDCl3) δ 33.0; IR (film) ν 2953, 1741,
1494, 1234, 1058, 1031, 825, 775, 750, 704.; HRMS (ESI) m/z calcd
for C16H20O3P (M + H)+ 291.1150, found 219.1156.
Dimethyl (3′-Methoxy-4-methylbiphenyl-2-yl)methylphos-
1
phonate (12g). Yield: 24.4 mg, 76%; yellow liquid; H NMR (400
MHz, CDCl3) δ 7.32 (dd, J = 13.4, 5.2 Hz, 2H), 7.15 (t, J = 10.7 Hz,
2H), 6.96−6.88 (m, 3H), 3.84 (s, 3H), 3.62 (s, 3H), 3.59 (s, 3H), 3.21
(s, 1H), 3.16 (s, 1H), 2.39 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ
159.4, 142.5, 139.7 (d, J = 10.4 Hz), 137.3, 131.0 (d, J = 4.9 Hz),
130.3, 129.2, 128.4 (d, J = 8.6 Hz), 127.8 (d, J = 3.4 Hz), 122.0, 115.1,
112.9, 55.3, 52.7 (d, J = 6.8 Hz), 29.3 (d, J = 138.3 Hz), 21.1.; 31P
NMR (162 MHz, CDCl3) δ 29.6.; IR (film) ν 2955, 1636, 1479, 1223,
1055, 1030, 810, 736, 706.; HRMS (ESI) m/z calcd for C17H22O4P
(M + H)+ 321.1256, found 321.1255.
Dimethyl (4′-Fluoro-4-methylbiphenyl-2-yl)methylphos-
1
phonate (12a). Yield: 28.7 mg, 93%; yellow liquid; H NMR (400
MHz, CDCl3) δ 7.33 (dd, J = 8.6, 5.5 Hz, 3H), 7.10 (dd, J = 11.3, 6.1
Hz, 4H), 3.62 (s, 3H), 3.59 (s, 3H), 3.15 (s, 1H), 3.10 (s, 1H), 2.39 (s,
3H).; 13C NMR (101 MHz, CDCl3) δ 162.1 (d, J = 246.1 Hz), 138.7
(d, J = 8.0 Hz), 137.4 (d, J = 3.4 Hz), 137.0 (s), 131.2 (d, J = 8.6 Hz),
131.1 (d, J = 5.5 Hz), 130.4 (d, J = 2.6 Hz), 128.5 (d, J = 8.6 Hz),
127.9 (d, J = 3.5 Hz), 115.1 (d, J = 21.2 Hz), 52.7 (d, J = 6.8 Hz), 29.4
(d, J = 138.5 Hz), 21.1.; 31P NMR (162 MHz, CDCl3) δ 29.3.; 19F
NMR (377 MHz, CDCl3) δ −115.7 (d, J = 3.0 Hz).; IR (film) ν 2955,
1634, 1489, 1223, 1159, 1032, 816, 735.; HRMS (ESI) m/z calcd for
C16H19O3PF (M + H)+ 309.1056, found 309.1053.
Dimethyl (3′,4-Dimethylbiphenyl-2-yl)methylphosphonate
(12h). Yield: 21.7 mg, 71%; yellow liquid; 1H NMR (400 MHz,
CDCl3) δ 7.34 (s, 1H), 7.32−7.27 (m, 1H), 7.19−7.08 (m, 5H), 3.59
(s, 3H), 3.56 (s, 3H), 3.21 (s, 1H), 3.15 (s, 1H), 2.39 (s, 6H).; 13C
NMR (101 MHz, CDCl3) δ 141.1, 139.9 (d, J = 8.2 Hz), 137.8, 137.1
(d, J = 3.4 Hz), 131.0 (d, J = 4.9 Hz), 130.4, 130.3 (d, J = 2.2 Hz),
128.1, 127.7 (d, J = 3.5 Hz), 127.7, 126.6, 52.6 (d, J = 6.7 Hz), 29.3 (d,
J = 137.9 Hz), 21.5, 21.1.; 31P NMR (162 MHz, CDCl3) δ 29.5.; IR
(film) ν 2953, 1634, 1614, 1456, 1250, 1056, 1032, 844, 735, 710.; HRMS
(ESI) m/z calcd for C17H22O3P (M + H)+ 305.1307, found 305.1308.
Dimethyl 5-Methyl-2-(naphthalen-2-yl)benzylphosphonate
(12i). Yield: 30.0 mg, 88%; yellow liquid; 1H NMR (400 MHz,
CDCl3) δ 7.94−7.81 (m, 4H), 7.56−7.47 (m, 3H), 7.39 (s, 1H), 7.24
(d, J = 7.8 Hz, 1H), 7.15 (d, J = 7.8 Hz, 1H), 3.58 (s, 3H), 3.56 (s,
3H), 3.24 (s, 1H), 3.18 (s, 1H), 2.42 (s, 3H).; 13C NMR (101 MHz,
CDCl3) δ 139.7 (d, J = 8.2 Hz), 138.6, 137.3 (d, J = 3.4 Hz), 133.3,
132.3, 131.1 (d, J = 4.9 Hz), 130.6 (d, J = 2.7 Hz), 128.6 (d, J = 8.6 Hz),
128.3, 128.0, 127.9, 127.9, 127.8, 127.7, 126.3, 126.0, 52.6 (d, J = 6.8 Hz),
29.4 (d, J = 138.2 Hz), 21.2.; 31P NMR (162 MHz, CDCl3) δ 29.5.; IR
(film) ν 2953, 1636, 1491, 1265, 1057, 1032, 895, 800, 735, 704.; HRMS
(ESI) m/z calcd for C20H22O3P (M + H)+ 341.1307, found 341.1303.
Dimethyl (2′-Fluoro-4-methylbiphenyl-2-yl)methylphos-
Dimethyl (3′-Fluoro-4-methylbiphenyl-2-yl)methyl-
1
phosphonate (12b). Yield: 27.5 mg, 89%; yellow liquid; H NMR
(400 MHz, CDCl3) δ 7.38−7.34 (m, 2H), 7.15−7.10 (m, 3H), 7.10−
7.05 (m, 2H), 3.62 (s, 3H), 3.59 (s, 3H), 3.18 (s, 1H), 3.12 (s, 1H),
2.39 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ 162.6 (d, J = 246.3 Hz),
143.3 (d, J = 7.7 Hz), 138.5 (d, J = 8.1 Hz), 137.7 (d, J = 3.5 Hz),
131.2 (d, J = 4.9 Hz), 130.2 (d, J = 2.8 Hz), 129.7 (d, J = 8.4 Hz),
128.4 (d, J = 8.6 Hz), 127.9 (d, J = 3.5 Hz), 125.4 (d, J = 2.6 Hz),
116.6 (d, J = 21.4 Hz), 113.9 (d, J = 20.9 Hz), 52.7 (d, J = 6.8 Hz),
29.4 (d, J = 138.5 Hz), 21.2.; 31P NMR (162 MHz, CDCl3) δ 29.2.;
19F NMR (377 MHz, CDCl3) δ −113.2.; IR (film) ν 2956, 1614, 1585,
1265, 1186, 1057, 1031, 852, 736.; HRMS (ESI) m/z calcd for
C16H19O3PF (M + H)+ 309.1056, found 309.1053.
Dimethyl (4′-Chloro-4-methylbiphenyl-2-yl)methylphos-
1
phonate (12c). Yield: 30.9 mg, 95%; yellow liquid; H NMR (400
MHz, CDCl3) δ 7.39 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 8.5 Hz, 3H),
7.11 (s, 2H), 3.62 (s, 3H), 3.60 (s, 3H), 3.15 (s, 1H), 3.09 (s, 1H),
2.39 (s, 3H).; 13C NMR (101 MHz, CDCl3) δ 139.5, 138.6 (d, J = 8.1
Hz), 137.6 (d, J = 3.4 Hz), 133.1, 131.2 (d, J = 4.9 Hz), 130.9, 130.3
(d, J = 2.8 Hz), 128.4, 127.9 (d, J = 3.5 Hz), 52.7 (d, J = 6.8 Hz), 29.4
(d, J = 138.6 Hz), 21.1.; 31P NMR (162 MHz, CDCl3) δ 29.2.; IR
(film) ν 2953, 1636, 1481, 1250, 1057, 1031, 815, 735.; HRMS (ESI)
m/z calcd for C16H19O3PCl (M + H)+ 325.0760, found 325.0760.
Dimethyl (3′-Cyano-4-methylbiphenyl-2-yl)methylphos-
1
phonate (12l). Yield: 4.0 mg, 13%; yellow liquid; H NMR (400
MHz, CDCl3) δ 7.38−7.28 (m, 3H), 7.20 (t, J = 7.1 Hz, 1H), 7.16−
7.10 (m, 3H), 3.56 (t, J = 13.5 Hz, 6H), 3.13 (d, J = 19.3 Hz, 2H), 2.40
(s, 3H).; 13C NMR (101 MHz, CDCl3) δ 159.5 (d, J = 245.9 Hz),
138.0 (d, J = 3.3 Hz), 133.1 (d, J = 8.2 Hz), 132.2, 131.1 (d, J = 5.1
Hz), 130.7, 129.7 (d, J = 9.0 Hz), 129.3 (d, J = 8.0 Hz), 128.3 (d, J =
17.6 Hz), 127.9 (d, J = 3.3 Hz), 124.1 (d, J = 3.6 Hz), 115.7 (d, J =
22.5 Hz), 52.6, 29.7 (d, J = 138.4 Hz), 21.2.; 31P NMR (162 MHz,
CDCl3) δ 29.1.; 19F NMR (377 MHz, CDCl3) δ −115.0.; IR (film) ν
2955, 1483, 1446, 1254, 1057, 1032, 814, 762.; HRMS (ESI) m/z
calcd for C16H19O3PF (M + H)+ 309.1056, found 309.1050.
Typical Procedure for the Horner−Wadsworth−Emmons
Reactions.15c To a mixture of dimethyl (4-methylbiphenyl-2-yl)-
methylphosphonate (8b) (29.1 mg, 0.1 mmol), n-Bu4NBr (6.4 mg,
0.02 mmol), and solid NaOH (6.4 mg, 0.02 mmol) in anhydrous
toluene (5.0 mL) at room temperature was added a toluene solution
(1 mL) of benzaldehyde (12.7 mg, 0.12 mmol), and the mixture was
vigorously stirred at 35 °C for 15 h under nitrogen. After completion
1
phonate (12d). Yield: 28.8 mg, 91%; yellow liquid; H NMR (400
MHz, CDCl3) δ 8.32 (s, 1H), 8.02 (d, J = 7.6 Hz, 1H), 7.53 (t, J = 7.6
Hz, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.25−7.20 (m, 2H), 7.15 (d, J = 8.0
Hz, 1H), 3.72 (s, 3H), 3.70 (s, 3H), 3.07 (s, 1H), 3.02 (s, 1H), 2.40 (s,
3H).; 13C NMR (101 MHz, CDCl3) δ 169.2, 140.3, 139.3 (d, J = 7.8
Hz), 137.6 (d, J = 3.7 Hz), 132.7, 132.1, 131.8 (d, J = 4.6 Hz), 130.1
(d, J = 2.9 Hz), 129.3, 128.9, 128.1 (d, J = 3.9 Hz), 127.3, 53.0 (d, J = 6.9
Hz), 30.3 (d, J = 138.8 Hz), 21.1.; 31P NMR (162 MHz, CDCl3) δ 29.8.;
IR (film) ν 2958, 1635, 1506, 1265, 1057, 1032, 812, 736.; HRMS (ESI)
m/z calcd for C17H19NO3P (M + H)+ 316.1103, found 316.1096.
Dimethyl (4-Methyl-4′-(trifluoromethyl)biphenyl-2-yl)-
methylphosphonate (12e). Yield: 26.2 mg, 73%; yellow liquid;
1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0
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of the reaction, H2O (1 mL) was added to the reaction mixture and
the mixture was extracted with diethyl ether (2 × 15 mL). The
combined organic extracts were washed with brine, dried over MgSO4,
and concentrated in vacuo. The resulting residue was purified by flash
chromatography on silica (100:1 hexane/ethyl acetate) to provide
compound 13a (21.9 mg, 81%).
Int. Ed. 2011, 50, 2450. (j) Arockiam, P. B.; Bruneau, C.; Dixneuf, P.
H. Chem. Rev. 2012, 112, 5879. (k) Song, G.; Wang, F.; Li, X. Chem.
Soc. Rev. 2012, 41, 3651. (l) Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-
Q. Acc. Chem. Res. 2012, 45, 788. (m) Wencel-Delord, J.; Glorius, F.
Nature Chem. 2013, 5, 369.
(5) For selected recent examples, see: (a) Satoh, T.; Miura, M.
Synthesis 2010, 3395. (b) Zhao, X.; Yeung, C. S.; Dong, V. M. J. Am.
Chem. Soc. 2010, 132, 5837. (c) Nishikata, T.; Abela, A. R.; Huang, S.;
Lipshutz, B. H. J. Am. Chem. Soc. 2010, 132, 4978. (d) Feng, C.; Loh,
T. P. Chem. Commun. 2011, 47, 10458. (e) Park, S. H.; Kim, J. Y.;
Chang, S. Org. Lett. 2011, 13, 2372. (f) Patureau, F. W.; Besset, T.;
Glorius, F. Angew. Chem., Int. Ed. 2011, 50, 1064. (g) Ackermann, L.;
Wang, L.; Wolfram, R.; Lygin, A. V. Org. Lett. 2012, 14, 728.
(h) Cheng, X. F.; Li, Y.; Su, Y.-M.; Yin, F.; Wang, J.-Y.; Sheng, J.; Vora,
H. U.; Wang, X.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2013, 135, 1236.
(i) Zhang, L.-S.; Chen, K.; Chen, G.; Li, B.-J.; Luo, S.; Guo, Q.-Y.;
Wei, J.-B.; Shi, Z.-J. Org. Lett. 2013, 15, 10.
(6) For selected recent examples, see: (a) Gao, K.; Lee, P.-S.; Fujita,
T.; Yoshikai, N. J. Am. Chem. Soc. 2010, 132, 12249. (b) Arockiam, P.
B.; Fischmeister, C.; Bruneau, C.; Dixneuf, P. H. Angew. Chem., Int. Ed.
2010, 49, 6629. (c) Gao, K.; Yoshikai, N. J. Am. Chem. Soc. 2011, 133,
400. (d) Tsai, A. S.; Tauchert, M. E.; Bergman, R. G.; Ellman, J. A. J.
Am. Chem. Soc. 2011, 133, 1248. (e) Gao, K.; Yoshikai, N. Angew.
Chem., Int. Ed. 2011, 50, 6888. (f) Kim, J. Y.; Park, S. H.; Ryu, J.; Cho,
S. H.; Kim, S. H.; Chang, S. J. Am. Chem. Soc. 2012, 134, 9110.
(E)-4-Methyl-2-styrylbiphenyl (13a). Yield: 21.9 mg, 81%,
1
colorless liquid; H NMR (400 MHz, CDCl3) δ 7.58 (s, 1H), 7.47−
7.33 (m, 7H), 7.30 (t, J = 7.6 Hz, 2H), 7.19 (dd, J = 23.5, 8.1 Hz, 3H),
7.07 (q, J = 16.3 Hz, 2H), 2.45 (s, 3H).; 13C NMR (101 MHz, CDCl3)
δ 140.9, 138.5, 137.7, 137.2, 135.2, 130.2, 129.9, 129.2, 128.6, 128.4,
128.1, 127.9, 127.4, 126.9, 126.9, 126.5, 21.2.; IR (film) ν 3024, 2922,
1598, 1261, 1072, 964, 908, 819, 769, 721, 700.; HRMS (ESI) m/z
calcd for C21H19 (M + H)+ 271.1487, found 271.1487.
(E)-2-(4-Chlorostyryl)-4-methylbiphenyl (13b). Yield: 23.7 mg,
1
78%, colorless liquid; H NMR (400 MHz, CDCl3) δ 7.55 (s, 1H),
7.48−7.32 (m, 5H), 7.31−7.23 (m, 5H), 7.17 (d, J = 7.8 Hz, 1H), 7.02
(dd, J = 38.9, 16.3 Hz, 2H), 2.44 (s, 3H).; 13C NMR (101 MHz,
CDCl3) δ 140.8, 138.6, 137.2, 136.2, 134.8, 133.0, 130.3, 129.9, 128.9,
128.7, 128.6, 128.1, 127.9, 127.7, 127.0, 126.4, 21.2.; IR (film) ν 3024,
2922, 1486, 1089, 1010, 964, 908, 812, 761, 732, 702.; HRMS (ESI)
m/z calcd for C21H18Cl (M + H)+ 305.1097, found 305.1091.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra. This material is available free of
charge via the Internet at http://pubs.acs.org.
(g) Schroder, N.; Wencel-Delord, J.; Glorius, F. J. Am. Chem. Soc.
̈
2012, 134, 8298. (h) Guin, S.; Rout, S. K.; Banerjee, A.; Nandi, A.;
Patel, B. K. Org. Lett. 2012, 14, 5294. (i) Johnson, D. G.; Lynam, J. M.;
Mistry, N. S.; Slattery, J. M.; Thatcher, R. J.; Whitwood, A. C. J. Am.
Chem. Soc. 2013, 135, 2222.
AUTHOR INFORMATION
Corresponding Author
*E-mail: sgkim@ntu.edu.sg.
■
(7) (a) Meng, X.; Kim, S. Org. Lett. 2013, 15, 1910. (b) Chan, L. Y.;
Kim, S.; Ryu, T.; Lee, P. H. Chem. Commun. 2013, 49, 4682.
(8) For Rh-catalyzed C-H activation using organophosphoryl
directing groups, see: (a) Unoh, Y.; Hashimoto, Y.; Takeda, D.;
Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2013, 15, 3258. (b) Park, S.;
Seo, B.; Shin, S.; Son, J.-Y.; Lee, P. H. Chem. Commun. 2013, 49, 8671.
(c) Seo, J.; Park, Y.; Jeon, I.; Ryu, T.; Park, S.; Lee, P. H. Org. Lett.
2013, 15, 3358. (d) Zhao, D.; Nimphius, C.; Lindale, M.; Glorius, F.
Org. Lett. 2013, 15, 4504. (e) Chary, B. C.; Kim, S. Org. Biomol. Chem.
2013, 11, 6879.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support from Nanyang
Technological University.
■
(9) (a) Wang, D.-H.; Mei, T.-S.; Yu, J.-Q. J. Am. Chem. Soc. 2008,
130, 17676. (b) Engle, K. M.; Thuy-Boun, P. S.; Dang, M.; Yu, J.-Q. J.
Am. Chem. Soc. 2011, 133, 18183.
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