FeCl3-Mediated arylation of α-hydroxyphosphonates with unactivated arenes: Pseudo-umpolung in allylic phosphonates

Article abstract of DOI:10.1002/ejoc.201201352

An FeCl₃-mediated regio- and stereoselective Friedel-Crafts-type arylation of α-hydroxy phosphonates with unactivated arenes has been developed in which the unstable allylphosphonate cations generated are stabilized by extended conjugation. The approach provides a simple, efficient and economic approach to highly demanding stereoselective γ-aryl- substituted vinylphosphonates and dialkyl (diarylmethyl)phosphonates with good regioselectivity. These reactions proceed under mild conditions and proceed in the absence of any additional solvent. Copyright

Full text of DOI:10.1002/ejoc.201201352

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
FULL PAPER
DOI: 10.1002/ejoc.201201352
FeCl3-Mediated Arylation of α-Hydroxyphosphonates with Unactivated Arenes:
Pseudo-Umpolung in Allylic Phosphonates
Gangaram Pallikonda[a] and Manab Chakravarty*[a]
Keywords: Synthetic methods / Umpolung / Allylic compounds / Phosphonates / Arenes / Iron
An FeCl3-mediated regio- and stereoselective Friedel–
Crafts-type arylation of α-hydroxy phosphonates with unacti-
vated arenes has been developed in which the unstable allyl-
phosphonate cations generated are stabilized by extended
conjugation. The approach provides a simple, efficient and
economic approach to highly demanding stereoselective γ-
aryl-substituted vinylphosphonates and dialkyl (di-
arylmethyl)phosphonates with good regioselectivity. These
reactions proceed under mild conditions and proceed in the
absence of any additional solvent.
have been reported in the literature for the synthesis of di-
ethyl (diarylmethyl)phosphonates that could extend the exi-
sting applications. Consequently, the synthesis of γ-aryl-
substituted vinylphosphonates[6a,6b] and diethyl (di-
arylmethyl)phosphonates[2] by a simple, efficient and econ-
omic approach is highly desirable.
Introduction
Research into organophosphonates,[1,2] in particular vi-
nylphosphonates,[1] has attracted considerable attention be-
cause of their significant biological properties[3] and wide-
spread applications in the field of materials sciences.[4] No-
tably, they are very well established as building blocks in the
synthesis of heterocyclic compounds[1b] and are also used
to increase flame retardancy in polymer sciences.[4c] γ-Aryl-
substituted vinylphosphonates are also frequently employed
in the synthesis of turmerone, an aromatic bisabolene ses-
quiterpene (Figure 1).[5] On the other hand, dialkyl (di-
arylmethyl)phosphonates are essential precursors for intro-
ducing the diarylethene moiety by the Horner–Wadsworth–
Emmons reaction (modified version of the famous Wittig
reaction) into a range of molecules with various applica-
tions (Figure 1). In spite of their widespread use, the scope
of these phosphonates is very limited due to their unavail-
ability with diverse substituents. Only dialkyl (di-
phenylmethyl)phosphonates have been reported, which
were prepared by the classical Michaelis–Arbuzov reaction
starting with benzhydryl bromide and trialkyl phosphite at
high temperatures with the generation of alkyl brom-
ide.[2g,2j] In another approach,[2i] harsh conditions were re-
quired for three days to achieve the desired product along
with starting materials and other unidentified compounds.
Thus, prolonged reaction times, harsh reaction conditions
and the production of copious waste make these methods
unattractive. However, as far as we know, no other methods
Figure 1. Examples of important molecules synthesized from γ-
substituted vinylphosphonates and diethyl diphenylmethylphos-
phonate.
Several transition-metal-mediated syntheses of organo-
phosphonates with different functionalities have been re-
ported.[1b,7] More significantly, Pd catalysts with expensive
phosphane ligands have been used for the regioselective
synthesis of γ-substituted vinylphosphonates starting from
α-acetoxy allylic phosphonates.[5,8] These reactions illustrate
the kind of umpolung reactivity of allylic phosphonates in
which the reactions proceed through the formation of allylic
phosphonate cations, which are difficult to generate due to
the electron-withdrawing effect of the phosphoryl group.[5,8]
[a] Department of Chemistry, Birla Institute of Technology and
Sciences, Pilani-Hyderabad Campus,
Jawahar nagar, Shamirpet Mondal, Hyderabad, AP-500078,
India
Fax: +91-40-66303998
E-mail: manabhere@yahoo.co.in
Homepage: http://universe.bits pilani.ac.in/hyderabad/
manabchakravarty/Profile
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201201352.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
G. Pallikonda, M. Chakravarty
FULL PAPER
However, because of the high cost of these metals as well was found that FeCl3 is the best system for this reaction.
as the relatively toxic nature of the associated ligands, there Although Friedel–Crafts-type reactions of benzylic acet-
is a need to look for inexpensive alternatives. In this respect, ates/alcohols have been reported with 10 mol-% FeCl3,[14]
FeIII-mediated organic transformations have shown poten- we needed 1 equiv. of FeCl3 to facilitate the departure of
tial benefits in organic synthesis.[9] The use of water-soluble the hydroxy group and complete the reaction (Scheme 1).[15]
FeCl3 as a mild and relatively non-toxic reagent for the acti-
Although the reaction was more favourable (6 h at room
vation of benzylic and allylic alcohols to generate the carbo- temp.) when performed with 3 equiv. of FeCl3, only 1 equiv.
cationic intermediate followed by addition to a nucleophile was used to avoid the formation of coloured impurities and
(Friedel–Crafts-type reaction) is very well established.[9b,10] waste. The reactions were very clean and almost quantita-
1
Hence, with this concept and an interest in the synthesis of tive conversions were observed by NMR (both H and 31P)
organophosphonates,[11] we report herein a new, simple and even before purification. We surmise that the carbocation is
facile FeCl3-mediated synthesis of γ-aryl-substituted vinyl- initially generated at the α carbon[16] and then is stabilized
phosphonates and diethyl (diarylmethyl)phosphonates at the γ carbon through conjugation. This reaction might
starting with the easily accessible α-hydroxyphosphonates be considered as a pseudo-umpolung given the reactivities
(1 and 4) under mild and solvent-free conditions.
of allylic phosphonates. Close scrutiny of highly resolved
1H and 13C NMR spectra of the regioisomeric mixture of
2a revealed the 3JP-H coupling constant (ca. 20.0 Hz) for β-
3
H and the JP-C coupling constant (ca. 21.0 Hz) for γ-C.
Results and Discussion
These data indicate that β-H and γ-C are cis and trans to
the phosphorus, respectively, in both the regioisomers (see
the Supporting Information for the extended spec-
trum).[5,17] The formation of the Z stereoisomer of 2a was
not observed under the reaction conditions employed, al-
though the Pd-catalysed arylation reactions of optically
pure or racemic allylic hydroxy phosphonates with (p-tolyl)-
tributylstannane[5] and other nucleophiles[6] gave a mixture
of E/Z isomers. The difference of 0.1 ppm in the 31P NMR
spectrum for the two regioisomers of 2a and comparative
studies of reported 31P NMR spectroscopic data for com-
pounds related to 2a suggest that the isomers of 2a are not
E/Z isomers but ortho/para regioisomers.[5,17] Also of inter-
est is the reaction in Scheme 2, in which the allylic alcohol
undergoes disproportionation to afford the corresponding
alkene and α,β-unsaturated ketone.[18] Under the same reac-
tion conditions, allylic alcohol 1a afforded only 2a with the
same regioselectivity as mentioned in Scheme 1. This dem-
onstrates the different electronic, steric and conjugation ef-
fects of the phosphonyl group compared with the phenyl
group and that make the phosphonate chemistry consider-
ably rich.
The difficulties involved in generating allylphosphonate
cations could be circumvented by introducing a carbocation
stabilizing group (e.g., allyl, phenyl and methyl) at the adja-
cent position or directly bonded to the carbocation stabi-
lized through a conjugation/inductive effect. In our initial
studies, allylphosphonate 1a was chosen as it is a very stable
crystalline, easily accessible, inexpensive material.[12] More-
over, similar kinds of allylic alcohols have been widely used
as precursors for the synthesis of synthetically and biolo-
gically important phosphonates.[13] The FeCl3-mediated re-
action of 1a with anhydrous toluene in nitromethane led to
the formation of a regioisomeric (ortho/para ca. 9:1) mix-
ture of (Ϯ)-(E)-γ-toluene-substituted vinylphosphonate 2a
(Scheme 1) in around 70% isolated yield at room tempera-
ture. Note that the FeCl3-catalysed benzylation of toluene
with 1-phenylethyl acetate afforded the product in more
than 99% yield with a regioselectivity of 84:13:3.[14] With a
view to a solvent-free approach, the reaction was performed
only in anhydrous toluene under the same reaction condi-
tions, which afforded 2a with identical selectivity. We opti-
mized the reaction conditions (see Table S1 in the Support-
ing Information) to obtain compound 2a (Scheme 1) in
good yields. A control experiment (without the use of any
metal) failed to undergo this reaction. With a view to cost
and accessibility, several Lewis acids [such as FeCl3,
FeCl3·6H2O, Fe(acac)3, FeCl2·H2O, ZnCl2, AlCl3,
CuCl2·2H2O, Cu(OAc)2·2H2O] and Brønsted acids (such as
AcOH and p-toluenesulfonic acid) were screened, and it
Scheme 2. FeCl3-catalysed disproportionation reaction of allylic
alcohol.[18]
Furthermore, to confirm the stereochemistry of the
product 2a, we also prepared the analogous solid com-
pound 3 starting from (Ϯ)-(E)-(OCH2CMe2CH2O)P(O)-
CH(OH)CH=CHPh in a manner similar to the preparation
of 2a. X-ray crystallographic analysis of a crystal obtained
from a dichloromethane (DCM)/hexane solution of com-
pound 3 revealed the E configuration (Figure 2).[19]
Scheme 1. FeCl3-mediated reaction of toluene with allylic hydroxy-
phosphonate 1a.
2
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
Arylation of α-Hydroxyphosphonates
Table 1. Synthesis of γ-aryl-substituted vinylphosphonates 2a–i.[a]
Figure 2. Molecular structure and ORTEP diagram (ellipsoids
drawn at the 20% probability level) for compound 3.
Next, we studied the reactions with different unactivated
arenes, which gave the expected products in good yields and
regioselectivities (Table 1). The reactions with toluene and
benzene proceeded at room temp., whereas the bulkier ar-
enes like o-xylene, mesitylene and durene needed a higher
temperature (70 °C). Dry dichloroethane (DCE) was used
as solvent in the case of durene and naphthalene (solid in
nature) to form a homogeneous mixture that might assist
the formation of products. The activated arene, anisole, gave
the product 2f as a regioisomeric mixture (ca. 1:2) along
with an α-arylated compound of type 2Ј[16] (ca. 7–8%,
Table 1, entry 6) at room temp. Being interested in the use
of naphthyl phosphonate systems as functional materials,[20]
our initial attempt at the reaction of naphthalene with
phosphonate 1a gave both the thermodynamically and ki-
netically controlled products, γ-naphthyl-substituted vinyl-
phosphonates, in a 1:1 regioisomeric ratio under the reac-
tion conditions (70 °C/8 h in DCE) although it needs more
detailed scrutiny. The acetate derivative of compound 1a
reacted readily with toluene in the presence of FeCl3 under
the reaction conditions employed to afford 2a in a similar
yield and selectivity to that obtained when starting from 1a.
The other inexpensive allylphosphonate 1b with a methyl
group at the γ carbon also underwent arylation reactions
with arenes in the presence of FeCl3 to afford compounds
2h and 2i in high yields. It is interesting to observe that
the single methyl group stabilizes the cation sufficiently. The
products 2b–i were assigned the E stereochemistry by analy-
1
sis of their H and/or 13C NMR spectra.
We also explored the scope of these FeCl3-mediated aryl-
ation reactions by using phosphonates 4a–c, which afforded
diethyl (diarylmethyl)phosphonates 5a–g in good yields and
with excellent regioselectivities under the mild conditions
(Table 2). As expected, the aryl groups of the phosphonates
should bear electron-donating substituents to stabilize the
carbocations and enable the reactions to proceed smoothly.
The reaction of 4b with toluene gave a mixture of three
regioisomers (probably ortho/para/meta 68:23:9), as indi-
cated in the 31P NMR spectrum of 5e. In addition, phos-
phonate 4c afforded 5g as a mixture of regioisomers, as an-
[a] Reaction conditions: phosphonate (1 mol equiv.), FeCl3
(1 mol equiv.) and arenes (2.0–20.0 mol equiv.) at room temp. for
entries 1, 2 and 6 and for the rest 70 °C was used. [b] The regiose-
lectivity ratio (ortho/para) was obtained by using integrated inten-
sity ratios of the 1H/31P NMR peaks. [c] DCE was used as solvent.
[d] Around 7–8% yield of a compound of type 2Ј was observed
along with the isolated compound.
ticipated. All these compounds 5a–g were very well charac- spectra and the appearance of a doublet in the region δ =
terized by identifying the doublet in the range δ = 4.35– 44.0–50.0 [J ≈ 135.0–144.0 Hz, P-C(α)H] in the 13C NMR
5.02 ppm [J ≈ 25.0–30.0 Hz, 1 H, P-C(α)H] in the 1H NMR spectra.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
G. Pallikonda, M. Chakravarty
FULL PAPER
Table 2. Synthesis of diethyl (diarylmethyl)phosphonates 5a–g.[a]
Conclusions
In this work, our initial efforts to develop a FeCl3-medi-
ated stereoselective method for the synthesis of γ-aryl-sub-
stituted vinylphosphonates and diethyl (diarylmethyl)phos-
phonates starting from easily accessible α-hydroxyphos-
phonates and unactivated arenes have been successful. We
believe that this atom economic, (additionally) solvent-free
and cheap method will open a new route to the synthesis
of several important phosphonates that could be used as
precursors for the synthesis of organic functional materials
as well as the analogues of natural products like turmerone.
Further studies in this area using heteroarenes and the syn-
thetic applications of these reactions and products are un-
derway in our laboratory.
Experimental Section
General: All reactions were carried out under nitrogen using a
Schlenk line or nitrogen-filled balloons. Solvents were purified by
distillation from appropriate drying agents under nitrogen. Organic
extracts were dried with anhydrous sodium sulfate. Solvents were
removed in a rotary evaporator under reduced pressure. Silica gel
(100–200 mesh size) was used for column chromatography. The re-
actions were monitored by TLC on silica gel 60 F254 (0.25 mm).
1H, 13C and 31P NMR spectra (1H, 400 or 500 MHz; 13C, 101 or
125 MHz; 31P, 162 or 212 MHz) were recorded with a 400 or
500 MHz spectrometer in CDCl3 with chemical shifts referenced to
SiMe4 (δ = 0 ppm) or 85% H3PO4 (δ = 0 ppm). IR spectra were
recorded with an FT-IR spectrophotometer. Melting points were
determined by using a local hot-stage melting-point apparatus. Ele-
mental analyses were carried out with a CHN analyser. Electron-
impact (EI) and chemical-ionization mass spectra were recorded
at 70 eV. Some mass spectra were also recorded by using LC–MS
equipment. The α-hydroxyphosphonates 1a–b,[12] 3,[21] 4a,[22] 4b[23]
and 4c[23] were prepared by using literature procedures.
General Procedure for the Synthesis of Vinylphosphonates 2a–i: An-
hydrous FeCl3 (0.30 g, 1.85 mmol equiv.) was added to a stirred
solution of 1a (0.50 g, 1.85 mmol) in anhydrous toluene (0.51 g, ca.
0.6 mL, 5.55 mmol)[24] and the reaction mixture was stirred at room
temp. for 12 h. After completion of the reaction, as indicated by
TLC, the reaction was quenched with a saturated NH4Cl Solution.
The aqueous layer was extracted with ethyl acetate (3ϫ20mL). Af-
ter filtration and removal of solvent in vacuo, the crude product
was purified by column chromatography using EtOAc/petroleum
ether (50:50) as the eluent to afford 2a as a regioisomeric mixture
(ca. 90:10). All the other compounds 2b–i were prepared analo-
gously using similar molar quantities unless stated otherwise.
Diethyl (؎)-(E)-3-Phenyl-3-(p-tolyl)prop-1-enylphosphonate (2a):
Yield 0.58 g (91%). Viscous liquid. IR (KBr): ν = 1627, 1448, 1247,
˜
1
1028 cm–1. H NMR (500 MHz, CDCl3): δ = 1.33 (t, J = 7.0 Hz,
6 H), 2.34 (s, 3 H), 4.06–4.13 (m, 4 H), 4.86 (d, J = 6.5 Hz, 1 H),
5.58 (ddd, J = 19.5, 17.9, 1.6 Hz, 1 H), 7.06–7.07 (m, 2 H), 7.13–
7.20 (m, 4 H), 7.22–7.27 (m, 2 H), 7.31–7.34 (m, 2 H) ppm. [The
corresponding characterization peaks for the other (10%) re-
gioisomer along with other peaks at δ = 5.45 (ddd, J = 19.7, 17.9,
1.8 Hz, 1 H) ppm prove the E stereoisomer for both regioisomers.]
13C NMR (125 MHz, CDCl3): δ = 16.4 (d, J = 6.1 Hz), 21.0, 54.7
(d, J = 21.4 Hz), 61.7 (d, J = 5.5 Hz), 118.8 (d, J = 185.5 Hz),
[a] Reaction conditions: phosphonate (1 mol equiv.), FeCl3
(1 mol equiv.) and arenes (3.0–20.0 mol equiv.) at room temp. for
entries 1, 2, 5 and 7 and for the rest 70 °C was required. [b] The
regioselectivity ratio was obtained by using integrated intensity ra-
1
tios of the H/31P NMR peaks. [c] DCE was used as solvent.
4
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
Arylation of α-Hydroxyphosphonates
126.8, 128.5, 128.6, 128.7, 129.3, 136.5, 138.2, 141.4, 154.2 (d, J =
5.6 Hz). [The corresponding characterization peak for the other
(10%) regioisomer along with other peaks at δ = 51.4 (d, J =
21.5 Hz), 119.1 (d, J = 185.5 Hz) ppm again support the E configu-
ration for both regioisomers.] 31P NMR (212 MHz, CDCl3): δ =
18.5 (s, ca. 90%) and 18.6 (s, ca. 10%) ppm. MS (70 eV): m/z =
345 [M + 1]+. C20H25O3P (344.39): calcd. C 69.75, H 7.32; found
C 69.88, H 7.17.
Diethyl
(؎)-[(E)-3-(4-Methoxyphenyl)-3-phenylprop-1-enyl]phos-
phonate (2f): The reaction was performed at room temp. for 12 h by
using anisole (3 equiv.). The product was isolated as a regioisomeric
mixture (ca. 32:60) along with a product of type 2Ј (ca. 8%), yield
0.55 g (83%). Viscous liquid. IR (KBr): ν = 1605, 1511, 1457, 1248,
˜
1029 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.31 (t, d, J = 7.2 Hz,
6 H), 3.76 and 3.7 (2 s, for both isomers in ca. 1:2 ratio, 3 H), 4.06–
4.09 (m, 4 H), 4.83 and 5.29 (2 br., 1 H), 5.53 (m, 1 H), 6.84–7.02
(m, 2 H), 7.05–7.08 (m, 2 H), 7.16–7.38 (m, 6 H) ppm; peak at δ =
6.5 (m) ppm appears due to the isomer of type 2Ј.[16] 13C NMR
(125 MHz, CDCl3): δ = 16.3 (d, J = 6.2 Hz), 54.2 (d, J = 21.2 Hz),
55.2, 61.8 (d, J = 6.2 Hz), 114.1, 118.7 (d, J = 186.2 Hz), 126.9,
128.2, 128.6, 128.7, 129.6, 133.2, 141.5, 154.4 (d, J = 6.2 Hz),
158.5 ppm. Peaks at δ = 48.0 (d, J = 22.5 Hz), 55.4, 61.7 (d, J =
5.0 Hz), 110.8, 118.2 (d, J = 186.2 Hz), 126.6, 128.4, 128.8, 129.4,
140.9, 154.3 (d, J = 6.2 Hz), 156.8 ppm along with other merged
peaks appear in the spectrum of the other regioisomer. 31P NMR
(162 MHz, CDCl3): δ = 18.6 (60%), 19.0 (32%), 25.1 (ca. 8%) ppm.
C20H25O4P (360.39): calcd. C 66.66, H 6.99; found C 66.78, H 6.89.
Diethyl [(E)-3,3-Diphenylprop-1-enyl]phosphonate (2b): In this case,
the reaction was stirred for only 6 h at room temp, yield 0.55 g
(90%). Brownish white solid, m.p. 48–50 °C. IR (KBr): ν = 1597,
˜
1495, 1457, 1248, 1023 cm–1. 1H NMR (400 MHz, CDCl3): δ =
1.31 (t, J = 7.1 Hz, 6 H), 4.04–4.11 (m, 4 H), 4.88 (d, J = 6.3 Hz,
1 H), 5.57 (ddd, J = 20.1, 17.1, 1.4 Hz, 1 H), 7.15–7.22 (m, 4 H),
7.24–7.27 (m, 3 H), 7.29–7.33 (m, 4 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 16.3 (d, J = 5.0 Hz), 55.1 (d, J = 21.2 Hz), 61.7 (d, J
= 6.2 Hz), 119.0 (d, J = 185.0 Hz), 126.9, 128.6, 128.7, 141.2, 154.0
(d, J = 5.0 Hz) ppm. 31P NMR (162 MHz, CDCl3): δ = 18.4
(s) ppm. C19H23O3P (330.36): calcd. C 69.08, H 7.02; found C
69.21, H 6.96.
Diethyl
(؎)-[(E)-3-(Naphthalen-1/2-yl)-3-phenylprop-1-enyl]phos-
phonate (2g): The reaction was performed with 1a (0.50 g,
1.85 mmol) and naphthalene (0.47 g, 3.70 mmol) at 70 °C for 6 h
using anhydrous 1,2-dichloroethane (4 mL) as solvent. The product
was isolated by column chromatography using EtOAc/hexane
(60:40) as an eluent as a mixture of two regioisomers in a ratio of
around 1:1, yield 0.59 g (84%). Thick, reddish viscous liquid. IR
Diethyl (؎)-[(E)-3-(3,4-Dimethylphenyl)-3-phenylprop-1-enyl]phos-
phonate (2c): The reaction was performed at 70 °C for 6 h and the
product was isolated as a regioisomeric mixture, yield 0.56 g (84%).
Viscous liquid. IR (KBr): ν = 1627, 1497, 1448, 1248, 1026 cm–1.
˜
1H NMR (400 MHz, CDCl3): δ = 1.31 (t, J = 6.8 Hz, 6 H), 2.23
and 2.22 (2 s, 6 H), 4.05–4.12 (m, 4 H), 4.81 (d, J = 6.4 Hz, 1 H),
5.57 (ddd, J = 20.5, 17.1, 1.6 Hz, 1 H), 6.88–6.93 (m, 2 H), 7.06–
7.17 (m, 3 H), 7.22–7.32 (m, 4 H) ppm. 13C NMR (101 MHz,
CDCl3): δ = 16.3 (d, J = 6.1 Hz), 19.2, 19.7, 54.6 (d, J = 21.2 Hz),
61.6 (d, J = 6.1 Hz), 118.8 (d, J = 187.8 Hz), 125.9, 126.7, 128.5,
128.5, 129.8, 135.0, 136.7, 138.5, 141.4, 126.8, 128.5, 128.6, 128.7,
129.3, 136.5, 138.2, 141.4, 154.2 (d, J = 5.0 Hz) ppm. 31P NMR
(162 MHz, CDCl3): δ = 18.6 ppm. C21H27O3P (358.42): calcd. C
70.37, H 7.59; found C 70.18, H 7.65.
(KBr): ν = 1627, 1599, 1449, 1245, 1025 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 1.28–1.35 (m, 6 H), 4.03–4.14 (m, 4 H), 5.05 (d, J =
6.3 Hz, 1 H), 5.48 (ddd, J = 19.9, 17.2, 1.6 Hz, 1 H), 7.19–7.46 (m,
7 H), 7.48–7.64 (m, 3 H), 7.78–7.96 (m, 3 H) ppm. The peak at δ
= 5.59–5.68 (m, not well resolved) merges with those of the other
isomer). Other peaks merge with those of the other isomer. 13C
NMR (125 MHz, CDCl3): δ = 16.4 (d, J = 6.2 Hz), 50.9 (d, J =
21.2 Hz), 61.8 (d, J = 5.0 Hz), 119.6 (d, J = 185.0 Hz), 123.8, 125.4,
125.7, 126.3, 127.0, 127.1, 127.6, 128.0, 128.7, 128.9, 131.5, 134.1,
136.9, 140.6, 153.8 (d, J = 6.2 Hz) ppm. The peaks at δ = 16.4 (d,
J = 6.25 Hz), 55.1 (d, J = 21.2 Hz), 61.8 (d, J = 5.0 Hz), 119.4 (d,
J = 186.2 Hz), 125.9, 126.6, 127.0, 127.1, 127.8, 128.4, 128.8, 128.9,
132.4, 133.4, 138.7, 141.1, 153.8 (d, J = 5.0 Hz) ppm merge with
those of the other regioisomer. 31P NMR (162 MHz, CDCl3): δ =
18.5 (s), 18.3 (s) (1:1) ppm. C23H25O3P (380.42): calcd. C 72.62, H
6.62; found C 72.85, H 6.58.
Diethyl (؎)-[(E)-3-Mesityl-3-phenylprop-1-enyl]phosphonate (2d):
This product was obtained after heating at 70 °C for 8 h, yield
0.59 g (86%). Viscous liquid. IR (KBr): ν = 1623, 1447, 1248,
˜
1
1026 cm–1. H NMR (400 MHz, CDCl3): δ = 1.31 (m, 6 H), 2.10
(s, 6 H), 2.28 (s, 3 H), 4.06–4.12 (m, 4 H), 5.35 (br., 1 H), 5.53–
5.72 (m, not well resolved, 1 H), 6.87 (s, 2 H), 7.11–7.22 (m, 5 H),
7.26–7.29 (m, 1 H) ppm. 13C NMR (101 MHz, CDCl3): δ = 16.3
(d, J = 6.1 Hz), 20.8, 21.4, 48.8 (d, J = 21.2 Hz), 61.7 (d, J =
6.1 Hz), 118.4 (d, J = 187.9 Hz), 126.3, 127.4, 128.5, 130.1, 134.6,
Diethyl (؎)-[(E)-3-Phenylbut-1-enyl]phosphonate (2h): Compound
2h was synthesized in a manner similar to compound 2a by starting
with 1b (0.5 g, 2.40 mmol) and anhydrous benzene (0.42 mL,
4.80 mmol) at 70 °C for 3 h, yield 0.59 g, (92%). Viscous liquid. IR
136.5, 137.0, 141.1, 152.6 (d,
J =
5.0 Hz) ppm. 31P NMR
(162 MHz, CDCl3): δ = 18.7 ppm. C22H29O3P (372.44): calcd. C
70.95, H 7.85; found C 70.69, H 7.78.
(KBr): ν = 2978, 1627, 1246, 1054, 1028 cm–1. 1H NMR (400 MHz,
˜
CDCl3): δ = 1.23–1.29 (m, 6 H), 1.39 (d, J = 7.2 Hz, 3 H), 3.55–
3.62 (m, 1 H), 4.01–4.07 (m, 4 H), 5.59 (ddd, J = 20.0, 17.2, 1.6 Hz,
1 H), 6.85–6.92 (m, 1 H), 6.96–7.30 (m, 5 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 16.3 (d, J = 6.1 Hz), 20.0, 43.6 (d, J =
21.2 Hz), 61.7 (d, J = 5.5 Hz), 115.6 (d, J = 187.8 Hz), 126.7, 127.3,
128.7, 142.9, 156.9 (d, J = 4.5 Hz) ppm. 31P NMR (162 MHz,
CDCl3): δ = 19.1 ppm. C14H21O3P (268.29): calcd. C 62.67, H 7.89;
found C 62.76, H 7.79.
Diethyl (؎)-[(E)-3-Phenyl-3-(2,3,5,6-tetramethylphenyl)prop-1-enyl-
]phosphonate (2e): The reaction was performed with 1a (0.50 g,
1.85 mmol) and durene (0.74 g, 5.55 mmol) at 70 °C in anhydrous
1,2-dichloroethane (4 mL) as solvent for 8 h, yield 0.62 g, (87%).
Off-white solid, m.p. 82–84 °C. IR (KBr): ν = 1623, 1468, 1445,
˜
1
1237, 1021 cm–1. H NMR (400 MHz, CDCl3): δ = 1.32 (m, 6 H),
2.01 (s, 6 H), 2.23 (s, 6 H), 4.06–4.12 (m, 4 H), 5.48 (br., 1 H),
5.57–5.66 (m, not well resolved, 1 H), 6.95 (s, 1 H), 7.11–7.21 (m,
5 H), 7.26–7.29 (m, 1 H) ppm. 13C NMR (101 MHz, CDCl3): δ = Diethyl (؎)-[(E)-3-Mesitylbut-1-enyl]phosphonate (2i): Compound
16.4 (d, J = 6.1 Hz), 17.3, 20.8, 48.8 (d, J = 22.2 Hz), 61.7 (d, J =
5.1 Hz), 118.3 (d, J = 188.9 Hz), 126.2, 127.2, 128.5, 130.9, 133.1,
2i was synthesized in a manner similar to compound 2h at 70 °C
for 5 h, yield 0.67 g (90%). Viscous liquid. IR (KBr): ν = 2978,
˜
134.6, 137.7, 141.6, 153.6 (d,
J
=
6.1 Hz) ppm. 31P NMR
1625, 1249, 1055, 1027 cm–1. 1H NMR (400 MHz, CDCl3): δ =
1.28 (t, J = 7.1 Hz, 6 H), 1.42 (d, J = 7.2 Hz, 3 H), 2.21 (s, 3 H),
2.23 (s, 6 H), 4.00–4.08 (m, 4 H, 1 H, merged), 5.58 (ddd, J = 20.0,
17.4, 2.6 Hz, 1 H), 6.79 (s, 2 H), 6.97–7.08 (m, 1 H) ppm. 13C NMR
(162 MHz, CDCl3): δ = 18.9 ppm. MS (70 eV): m/z = 387
[M + 1]+. C23H31O3P (386.47): calcd. C 71.48, H 8.01; found C
71.25, H 8.16.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
G. Pallikonda, M. Chakravarty
FULL PAPER
(101 MHz, CDCl3): δ = 16.4 (d, J = 6.3 Hz), 16.9, 20.6, 21.0, 37.9 8.7 Hz), 130.5 (d, J = 7.5 Hz), 137.2 (d, J = 3.7 Hz), 158.7 ppm.
(d, J = 21.2 Hz), 61.5 (d, J = 5.4 Hz), 114.9 (d, J = 189.1 Hz),
129.9, 135.9, 136.2, 136.5, 157.5 (d, J = 4.7 Hz) ppm. 31P NMR
(162 MHz, CDCl3): δ = 19.6 ppm. C17H27O3P (310.37): calcd. C
65.79, H 8.77; found C 65.71, H 8.86.
31P NMR (162 MHz, CDCl3): δ = 25.4 (s) ppm. C18H23O4P
(334.35): calcd. C 64.66, H 6.93; found C 64.76, H 6.85.
Diethyl (؎)-Mesityl(4-methoxyphenyl)methylphosphonate (5c): The
reaction mixture was stirred at 70 °C for 8 h, yield 0.25 g (91%).
(؎)-(E)-5,5-Dimethyl-2-[3-phenyl-3-(p-tolyl)propenyl]-1,3,2-dioxa-
phosphinane 2-Oxide (3): The reaction was performed in a manner
similar to that used for the preparation of compound 2a by starting
with (Ϯ)-(E)-(OCH2CMe2CH2O)P(O)CH(OH)CH=CHPh (0.20 g,
0.71 mmol) and FeCl3 (0.115 g, 0.71 mmol) in 2 mL toluene for 6 h
at room temp. The product was isolated as a regioisomeric mixture
by chromatography with EtOAc/petroleum ether (40:60), yield
Off-white solid, m.p. 94–96 °C. IR (KBr): ν = 2917, 1509, 1256,
˜
1
1015 cm–1. H NMR (400 MHz, CDCl3): δ = 1.01 (t, J = 7.2 Hz,
3 H), 1.34 (t, J = 7.2 Hz, 3 H), 2.06, 2.25, 2.47 (3 s, each for 3 H),
3.39–3.78 (m, 1 H), 3.78 (s, 3 H), 3.83–3.88 (m, 1 H), 4.09–4.24 (m,
2 H), 5.02 (d, J = 30.8 Hz, 1 H), 6.76 (s, 1 H), 6.80 (d, J ≈ 8.8 Hz,
2 H), 6.89 (s, 1 H), 7.33 (d, J ≈ 8.8 Hz, 2 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 16.2 (d, J = 5.6 Hz), 16.4 (d, J = 6.1 Hz),
20.8, 21.4, 21.7, 43.9 (d, J = 144.0 Hz), 55.2, 61.4 (d, J = 7.4 Hz),
62.8 (d, J = 6.7 Hz), 113.6, 128.9, 129.4, 129.8, 129.9, 131.1, 136.5
(d, J = 2.8 Hz), 137.7 (d, J = 7.4 Hz), 139.3 (d, J = 3.8 Hz),
157.8 ppm. A peak at δ = 29.7 ppm is also observed in the spec-
trum. 31P NMR (162 MHz, CDCl3): δ = 26.5 (s) ppm. C21H29O4P
(376.43): calcd. C 67.01, H 7.77; found C 67.12, H 7.63.
0.22 g (87%). Brownish solid, m.p. 113–115 °C. IR (KBr): ν = 1633,
˜
1511, 1468, 1258, 1059 cm–1. 1H NMR (400 MHz, CDCl3): δ =
1.03 and 1.08 (2 s, 6 H), 2.33 (s, 3 H), 3.77–3.83 (m, 2 H), 4.18–
4.23 (m, 2 H), 4.87 (d, J = 8 Hz, 1 H), 5.61 (ddd, J = 21.4, 17.2,
1.7 Hz, 1 H), 7.04–7.06 (m, 1 H), 7.12–7.24 (m, 3 H), 7.27–7.34 (m,
6 H) ppm. The peaks at δ = 0.97, 1.00, 2.24, 6.52–6.53 (m) arise due
to the presence of the other isomer (ca. 4%). 13C NMR (125 MHz,
CDCl3): δ = 21.0, 21.4, 21.7, 32.5 (d, J = 5.0 Hz), 54.8 (d, J =
21.2 Hz), 75.3 (d, J = 6.2 Hz), 116.7 (d, J = 186.2 Hz), 126.9, 128.5,
128.6, 128.7, 129.4, 136.7, 137.7, 141.2, 156.4 (d, J = 6.2 Hz) ppm.
31P NMR (101 MHz, CDCl3): δ = 14.2 (s) ppm. A small peak near
δ = 21.0 ppm was observed that arise from the isomer of type 2Ј.
C21H25O3P (356.40): calcd. C 70.77, H 7.07; found C 70.62, H 7.16.
We crystallized this sample from DCM/hexane (2:8). An X-ray
structural analysis was performed on this crystal to confirm the
stereochemistry of 2a.
Diethyl
(؎)-(4-Methoxyphenyl)(naphthalenyl)methylphosphonate
(5d): This reaction was performed with 4a (0.20 g, 0.73 mmol) and
naphthalene (0.187 g, 1.46 mmol) in anhydrous 1,2-dichloroethane
(4 mL) at 70 °C for 6 h. The product was isolated by column
chromatography as a regioisomeric mixture in a ration of around
1:3 using 70% EtOAc/petroleum ether, yield 0.25 g (89%). Thick
red viscous liquid. IR (KBr): ν = 2980, 1607, 1510, 1252,
˜
1
1027 cm–1. H NMR (500 MHz, CDCl3): δ = 1.04–1.15 (m, 6 H),
3.74 (s, 3 H), 3.81–4.06 (m, 4 H, merged with peaks due to the
other isomer), 5.28 (d, J = 25.0 Hz, 1 H), 6.84 (d, J = 8.7 Hz, 2
H), 7.44–7.55 (m, 4 H, merged with peaks due to the other isomer),
7.78–7.86 (m, 3 H), 8.09 (d, J = 6.7 Hz, 1 H), 8.28 (d, J = 6.7 Hz,
1 H) ppm. The peaks at δ = 1.16–1.21 (m, 6 H), 3.78 (s, 3 H), 4.59
(d, J = 25.0 Hz, 1 H), 6.89 (d, J = 8.7 Hz, 2 H), 7.65 (d, J = 6.7 Hz,
1 H), 8.04 (br., 1 H) ppm along with other merged peaks appear
in the spectrum for the other regioisomer in a ratio of 1:3. 13C
NMR (125 MHz, CDCl3): δ = 16.2 (d, J = 6.2 Hz), 45.0 (d, J =
143.7 Hz), 55.2, 62.6 (d, J = 6.2 Hz), 113.9 (d, J ≈ 2.5 Hz), 123.1,
125.5, 126.4, 127.4 (d, J = 6.2 Hz), 127.9, 128.0, 128.2, 128.6 (d, J
= 5.0 Hz), 129.0, 130.7 (d, J = 6.2 Hz), 131.7 (d, J = 12.5 Hz),
134.2, 158.7 (d, J = 2.5 Hz) ppm. The peaks at δ = 16.4 (d, J =
6.2 Hz), 50.4 (d, J = 142.5 Hz), 55.2, 62.7 (d, J = 6.2 Hz), 113.0 (d,
J ≈ 1.3 Hz), 125.4, 125.9, 126.1, 127.6 (d, J ≈ 6.2 Hz), 128.0, 128.1,
128.8 (d, J = 5.0 Hz), 130.6 (d, J = 6.2 Hz), 132.4 (d, J = 2.5 Hz),
132.9 (d, J = 2.5 Hz), 133.4 (d, J = 1.2 Hz), 134.8 (d, J = 5.0 Hz),
158.7 (d, J = 1.2 Hz) ppm also appear for the other isomer. 31P
NMR (162 MHz, CDCl3): δ = 26.1 (s), 25.3 (s) ppm; signals are
present in an isomeric ratio of 1:3. C22H25O4P (384.41): calcd. C
68.74, H 6.56; found C 68.85, H 6.49.
General Procedure for the Synthesis of Diethyl (Diarylmethyl)phos-
phonates 5a–d: Anhydrous FeCl3 (0.118 g, 0.73 mmol) was added
to a stirred solution of 4a (0.20 g, 0.73 mmol) in anhydrous toluene
(0.20 g, 0.23 mL, 2.19 mmol)[24] and the reaction mixture was
stirred at room temp. for 12 h. After completion of the reaction, as
indicated by TLC, the mixture was quenched with a saturated
NH4Cl solution. The aqueous layer was extracted with ethyl acetate
(3ϫ 10 mL). After filtration and removal of the solvent in vacuo,
the crude product was purified by column chromatography using
EtOAc/petroleum ether (50:50) as eluent to afford 5a as a re-
gioisomeric mixture (ca. 97:3). Compounds 5b–d were prepared
analogously using similar molar quantities unless stated otherwise.
Diethyl (؎)-(4-Methoxyphenyl)(p-tolyl)methylphosphonate (5a):
Yield 0.235 g (92%). Viscous liquid. IR (KBr): ν = 2925, 1511,
˜
1253, 1029 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1.13 (t, J =
7.1 Hz, 6 H), 2.31 (s, 3 H), 3.77 (s, 3 H), 3.80–3.86 (m, 2 H), 3.93–
4.03 (m, 2 H), 4.35 (d, J = 25.2 Hz, 1 H), 6.84 (d, J ≈ 8.0 Hz, 2
H), 6.84 (d, J ≈ 8.0 Hz, 2 H), 7.38–7.44 (m, 4 H) ppm. 13C NMR
(101 MHz, CDCl3): δ = 16.3 (d, J = 5.2 Hz), 21.0, 49.9 (d, J =
139.1 Hz), 55.2, 62.6 (d, J = 6.9 Hz), 113.9, 129.1, 129.2, 130.4,
130.5, 134.1, 136.6, 158.6 ppm. 31P NMR (162 MHz, CDCl3): δ =
25.6 (s) ppm. A tiny peak at δ = 26.3 (ca. 3%) in the 31P NMR
spectrum is observed arising from a regioisomer. LC–MS: m/z =
349 [M + 1]+. C19H25O4P (348.38): calcd. C 65.51, H 7.23; found
C 65.46, H 7.15.
Diethyl (؎)-(m-Tolyl)(p-tolyl)methylphosphonate (5e): Compound
5e was prepared in a manner similar to compound 5a by mixing
4b (0.100 g, 0.387 mmol) and anhydrous FeCl3 (0.062 g,
0.387 mmol) in anhydrous toluene (0.5 mL, ca. 12 mmol) to afford
5e as a regioisomeric mixture (ca. 68:23:9), yield 0.112 g (87%).
Viscous liquid. IR (KBr): ν = 2924, 1605, 1248, 1022 cm–1. 1H
˜
Diethyl (؎)-(4-Methoxyphenyl)(phenyl)methylphosphonate (5b): The
reaction mixture was stirred at room temp. for 6 h, yield 0.22 g
NMR (400 MHz, CDCl3): δ = 1.08–1.16 (m, 6 H), 2.31 and 2.32
(2 s, 6 H), 3.78–3.88 (m, 2 H), 3.93–4.03 (m, 2 H), 4.35 (d, J =
25.2 Hz, 1 H), 7.03–7.21 (m, 4 H), 7.29–7.42 (m, 4 H) ppm. The
peaks at δ = 2.34 (s), 4.64 (d, J = 25.6 Hz) and 7.93 (d, J =
8 Hz) ppm along with other merged peaks appear in the spectrum
(90%). Off-white solid, m.p. 35–38 °C. IR (KBr): ν = 2927, 1511,
˜
1
1254, 1028 cm–1. H NMR (400 MHz, CDCl3): δ = 1.11–1.15 (m,
6 H), 3.78 (s, 3 H), 3.80–3.87 (m, 2 H), 3.96–4.02 (m, 2 H), 4.38
(d, J = 25.2 Hz, 1 H), 6.85 (d, J ≈ 8.8 Hz, 2 H), 7.21–7.33 (m, 3 for the other regioisomers. 13C NMR (125 MHz, CDCl3): δ = 16.2
H), 7.45 (d, J ≈ 8.4 Hz, 2 H), 7.51 (d, J ≈ 7.2 Hz, 2 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 16.3, 50.5 (d, J = 137.5 Hz), 55.2,
62.7, 113.9, 127.0, 128.5, 128.9 (d, J = 5.0 Hz), 129.3 (d, J =
(many lines), 20.1, 21.0, 21.5, 50.8 (d, J = 136.2 Hz), 62.7 (many
lines), 126.4 (d, J = 7.5 Hz), 127.8 (d, J = 2.5 Hz, along with other
merged peaks), 128.4, 129.2, 130.1 (d, J = 7.5 Hz), 130.6 (d, J =
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
Arylation of α-Hydroxyphosphonates
8.7 Hz), 133.9 (d, J = 3.7 Hz), 136.7 (d, J = 2.5 Hz), 136.9 (d, J = moy and Dr. Ram Suresh for helping to obtain the analytical data.
5.0 Hz), 138.1 (d, J = 1.2 Hz) ppm. The peaks at δ = 46.6 (d, J =
137.5 Hz), 51.0 (d, J = 137.5 Hz), 126.2 (d, J = 1.5 Hz), 126.5 (d,
J = 6.2 Hz), 126.9 (d, J = 7.5 Hz), 127.1 (d, J = 2.5 Hz), 128.3 (d,
J = 1.2 Hz), 129.3, 129.5 (d, J = 5.0 Hz), 130.2 (d, J = 7.5 Hz),
130.4 (d, J = 7.5 Hz), 135.3 (d, J = 5.0 Hz), 136.2 (d, J = 6.2 Hz),
136.3, 136.4, 136.8 (d, J = 5.0 Hz), 137.9 (d, J = 1.2 Hz) ppm arise
from the other isomers. 31P NMR (212 MHz, CDCl3): δ = 25.4
(s) ppm. The peaks at δ = 25.3 (9%) and 26.1 (ca. 23%) ppm ap-
pear in the spectrum for the other regioisomers. C19H25O3P
(332.38): calcd. C 68.66, H 7.58; found C 68.45, H 7.71.
Special thanks go to Dr. E. Balaraman for his valuable suggestions
while writing the manuscript.
[1] a) T. Janecki, J. Kedzia, T. Wasek, Synthesis 2009, 1227; b)
˛
˛
V. M. Dembitsky, A. A. A. Quntar, A. Haj-Yehia, M. Srebnik,
Mini-Rev. Org. Chem. 2005, 2, 91; c) T. Minami, T. Okauchi,
R. Kouno, Synthesis 2001, 349; d) T. Minami, J. Motoyoshiya,
Synthesis 1992, 333.
[2] a) G. Mao, A. Orita, L. Fenenko, M. Yahiro, C. Adachi, J.
Otera, Mater. Chem. Phys. 2009, 115, 378; b) C. L. Chiang, C.-
F. Shu, C.-T. Chen, Org. Lett. 2005, 7, 3717; c) J. Motoyoshiya,
T. Ikeda, S. Tsuboi, T. Kusaura, Y. Takeuchi, S. Hayashi, S.
Yoshioka, Y. Takaguchi, H. Aoyama, J. Org. Chem. 2003, 68,
5950; d) M. J. Plater, T. Jackson, Tetrahedron 2003, 59, 4673;
e) D. Armesto, A. Ramos, E. P. Mayoral, M. J. Ortiz, A. R.
Agarrabeitia, Org. Lett. 2000, 2, 183; f) D. Armesto, M. J. Or-
tiz, A. R. Agarrabeitia, J. Org. Chem. 1999, 64, 1056; g) C. Ha,
J. H. Homer, M. Newcomb, T. R. Varick, J. Org. Chem. 1993,
58, 1194; h) H. E. Zimmerman, R. T. Klun, Tetrahedron 1978,
34, 1775; i) A. C. Poshkus, J. E. Herweh, J. Org. Chem. 1964,
64, 1056; j) B. E. Smith, A. Burger, J. Am. Chem. Soc. 1953,
75, 5891.
[3] a) R. Engel, Chem. Rev. 1977, 77, 349; b) M. R. Harnden, A.
Parkin, M. J. Parratt, R. M. Perkins, J. Med. Chem. 1993, 36,
1345; c) R. R. Breaker, G. R. Gough, P. T. Gilham, Biochemis-
try 1993, 32, 9125; d) J. T. Whitteck, W. Ni, B. M. Griffin, A. C.
Eliot, P. M. Thomas, N. L. Kelleher, W. W. Metcalf, W. A.
van der Donk, Angew. Chem. 2007, 119, 9247; Angew. Chem.
Int. Ed. 2007, 46, 9089; e) Z. A. Doddridge, R. D. Bertram,
C. J. Hayes, P. Soultanas, Biochemistry 2003, 42, 3239; f) R.
Hirschmann, A. B. Smith III, C. M. Taylor, P. A. Benkovic,
S. D. Taylor, K. M. Yager, P. A. Sprengeler, S. J. Benkovic, Sci-
ence 1994, 265, 234.
Diethyl (؎)-Mesityl(m-tolyl)methylphosphonate (5f): The reaction
mixture of 4b (0.80 g, 3.10 mmol) and anhydrous FeCl3 (0.50 g,
3.10 mmol) in anhydrous mesitylene (2 mL) was stirred at 80 °C for
8 h. The product was isolated in pure form by column chromatog-
raphy using EtOAc/petroleum ether (70:30) as eluent, yield 0.92 g
(82%). White crystalline solid, m.p. 86–90 °C. IR (KBr): ν = 1606,
˜
1
1448, 1246, 1021 cm–1. H NMR (400 MHz, CDCl3): δ = 1.02 (t,
J = 6.8 Hz, 3 H), 1.34 (t, J = 6.8 Hz, 3 H), 2.07, 2.26, 2.29 (3 s,
each for 3 H), 2.48 (s, 3 H), 3.41–3.45 (m, 1 H), 3.84–3.86 (m, 1
H), 4.09–4.26 (m, 2 H), 5.03 (d, J = 30.8 Hz, 1 H), 6.77 (s, 1 H),
6.91 (s, 1 H), 7.01 (d, J ≈ 7.6 Hz, 1 H), 7.4–7.19 (m, 2 H), 7.25 (s,
1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 16.2 (d, J = 5.0 Hz),
16.4 (d, J = 6.2 Hz), 20.8, 21.4, 21.5, 21.7, 44.7 (d, J = 141.2 Hz),
61.4 (d, J = 7.5 Hz), 62.8 (d, J = 6.3 Hz), 125.9 (d, J = 11.2 Hz),
126.9, 128.0, 128.9, 129.4 (d, J = 11.2 Hz), 131.0 (d, J = 6.2 Hz),
131.1 (d, J = 2.5 Hz), 136.5 (d, J = 3.7 Hz), 137.4, 137.7, 137.8 (d,
J = 6.2 Hz), 139.4 (d, J = 3.8 Hz) ppm. 31P NMR (162 MHz,
CDCl3): δ = 26.3 (s) ppm. C21H29O3P (360.43): calcd. C 69.98, H
8.11; found C 70.12, H 8.02.
[4] a) S. Monge, B. Canniccioni, A. Graillot, J.-J. Robin, Biomacro-
molecules 2011, 12, 1973; b) C. Queffélec, M. Petit, P. Janvier,
D. A. Knight, B. Bujoli, Chem. Rev. 2012, DOI: 10.1021/
cr2004212; c) G. David, C. Negrell-Guirao, F. Iftene, B. Boute-
vin, K. Chougrani, Polym. Chem. 2012, 3, 265; d) S. Jin, K. E.
Gonsalves, Macromolecules 1998, 31, 1010; e) J. R. Ebdon, Re-
cent Adv. Flame Retard. Polym. Mater. 1997, 8, 161.
[5] a) J. R. Bradley, C. D. Spilling, J. Org. Chem. 2003, 68, 9502;
b) J. R. Bradley, S. Jeffrey, C. D. Spilling, Phosphorus Sulfur
Silicon Relat. Elem. 2002, 177, 1881.
[6] a) N. Rabasso, A. Fadel, Tetrahedron Lett. 2010, 51, 60; b) C.
Yuan, J. Yao, S. Li, Phosphorus Sulfur Silicon Relat. Elem.
1990, 53, 21; c) T. Janecki, A. Albrecht, J. F. Koszuk, J. Mod-
ranka, D. Słowak, Tetrahedron Lett. 2010, 51, 2274.
[7] For Cu, see: a) L. Rout, S. Rregati, C.-G. Zhao, Adv. Synth.
Catal. 2011, 353, 3340; for Ti, see: b) A. A. Quntar, V. M.
Dembitsky, M. Srebnik, Org. Lett. 2003, 5, 357; for Zr, see: c)
A. Quntar, M. Srebnik, Org. Lett. 2001, 3, 1379; for Ru, see:
d) A. Chatterjee, K. T.-L. Choi, R. H. Grubbs, Synlett 2001,
1034; for Ni, see: e) A. Fadel, F. Legrand, G. Evano, N. Rab-
asso, Adv. Synth. Catal. 2011, 353, 263; for Zn, see: f) R. J.
Barney, R. M. Richardson, D. F. Wiemer J. Org. Chem. 2011,
76, 2875; for Mn, see: g) K. V. Sajna, K. C. Kumara Swamy, J.
Org. Chem. 2012, 77, 8712; for a review, see: h) J. D. Sellars,
P. G. Steel, Chem. Soc. Rev. 2011, 40, 5170.
Diethyl (؎)-(3,4-Dimethoxyphenyl)(p-tolyl)methylphosphonate (5g):
Compound 5g was prepared in a manner similar to the preparation
of 5a by mixing 4c (0.1 g, 0.329 mmol) and anhydrous FeCl3
(0.053 g, 0.329 mmol) in anhydrous toluene (1 mL) at room temp.
for 12 h. The crude product was purified by column chromatog-
raphy using EtOAc/petroleum ether (80:20) as the eluent to afford
5g as a regioisomeric mixture (ca. 93:7), yield 0.102 g (82%). Vis-
1
cous liquid. IR (KBr): ν = 1599, 1510, 1256, 1015 cm–1. H NMR
˜
(400 MHz, CDCl3): δ = 1.14 (t, J = 7.2 Hz, 6 H), 2.30 (s, 3 H),
3.84 (s, 3 H), 3.87 (s, 3 H), 3.91–4.02 (m, 4 H), 4.33 (d, J = 25.2 Hz,
1 H), 6.80 (d, J ≈ 9.2 Hz, 1 H), 7.04 (d, J ≈ 8.8 Hz, 1 H), 7.11 (s,
1 H), 7.12 (d, J ≈ 8.0 Hz, 2 H), 7.40 (d, J ≈ 7.6 Hz, 2 H) ppm. The
peaks at δ = 2.34 (s), 4.62 (d, J = 26.4 Hz) ppm are observed for
the other regioisomer (ca. 7%). 13C NMR (101 MHz, CDCl3): δ =
16.3, 21.0, 50.2 (d, J = 139.1 Hz), 55.8 (2 s), 62.6 (d, J = 6.9 Hz),
111.1, 112.6 (d, J = 7.8 Hz), 121.6, (d, J = 8.7 Hz), 129.1, 129.2,
129.3, 133.9, 136.7, 148.0, 148.7 ppm. 31P NMR (162 MHz,
CDCl3): δ = 25.5 (s), 26.2 ppm, observed in a ratio of around 93:7.
LC–MS: m/z = 379 [M + 1]+. C20H27O5P (378.40): calcd. C 63.48,
H 7.19; found C 63.36, H 7.28.
Supporting Information (see footnote on the first page of this arti-
1
cle): Optimization table; copies of H/13C/31P NMR spectra.
[8] a) J. Zhu, X. Lu, Tetrahedron Lett. 1987, 28, 1897; b) J. Zhu,
X. Lu, J. Chem. Soc., Chem. Commun. 1987, 1318; c) X. Lu, J.
Sun, J. Zhu, Heteroat. Chem. 1992, 3, 551.
[9] For reviews, see: a) C. Bolm, J. Legros, J. L. Paih, L. Zani,
Chem. Rev. 2004, 104, 6217; b) D. D. Díaz, P. O. Miranda, J. I.
Padrón, V. S. Martín, Curr. Org. Chem. 2006, 10, 457.
[10] a) U. Jana, S. Biswas, S. Maiti, Tetrahedron Lett. 2007, 48,
4065; b) P. Salehi, N. Iranpoor, F. K. Behbahani, Tetrahedron
1998, 54, 943.
Acknowledgments
The authors thank the Department of Science and Technology
(DST), FAST TRACK for financial support. The authors are also
highly thankful to Mr. Satish, Mr. Swamy, Mr. Ramesh, Dr. Tan-
[11] a) K. V. Sajna, R. Kotikalapudi, M. Chakravarty, N. N. Bhu-
van Kumar, K. C. Kumara Swamy, J. Org. Chem. 2011, 76, 920;
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
G. Pallikonda, M. Chakravarty
FULL PAPER
b) M. Phani Pavan, M. Chakravarty, K. C. Kumara Swamy,
Eur. J. Org. Chem. 2009, 5927; c) M. Chakravarty, K. C. Kum-
ara Swamy, J. Org. Chem. 2006, 71, 9128.
[12]
[13]
F. Texier-Boullet, A. Foucaud, Synthesis 1982, 165.
a) R. Kotikalapudi, K. C. Kumara Swamy, Tetrahedron Lett.
2012, 53, 3831; b) A. He, N. Sutivisedsak, C. D. Spilling, Org.
Lett. 2009, 11, 3124; c) B. Yan, C. D. Spilling, J. Org. Chem.
2008, 73, 5385; d) H. Shabany, C. D. Spilling, Tetrahedron Lett.
1998, 39, 1465; e) E. Öhler, S. Kotzinger, Synthesis 1993, 497;
f) G. M. Blackburn, D. E. Kent, J. Chem. Soc., Chem. Com-
mun. 1981, 511.
[17] a) A. A. A. Quntar, M. Srebnik, J. Org. Chem. 2001, 66, 6650;
b) X.-Y. Jiao, W. G. Bentrude, J. Org. Chem. 2003, 68, 3303; c)
S. Ma, H. Guo, F. Yu, J. Org. Chem. 2006, 71, 6634.
[18] J. Wang, W. Huang, Z. Zhang, X. Xiang, R. Liu, X. Zhou, J.
Org. Chem. 2009, 74, 3299.
[19] CCDC-898273 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[14] I. Iovel, K. Mertins, J. Kischel, A. Zapf, M. Beller, Angew.
Chem. 2005, 117, 3981; Angew. Chem. Int. Ed. 2005, 44, 3913.
[15] M. Noji, Y. Konno, K. Ishii, J. Org. Chem. 2007, 72, 5161.
[16] The α-arylated compounds of type 2Ј were presumably ob-
served in yields of 5–8%. These compounds were not isolated
in the pure state and were partially characterized by multinu-
clear NMR spectroscopy. For the reactions with toluene,
xylene and anisole, the NMR analyses showed a multiplet in
[20] J. C. Amicangelo, W. R. Leenstra, Inorg. Chem. 2005, 44, 2067,
and references cited therein.
[21] C. Muthiah, K. Praveen Kumar, C. Aruna Mani, K. C. Kum-
ara Swamy, J. Org. Chem. 2000, 65, 3733.
[22] A. Y. Platonov, A. A. Sivakov, K. N. Chistokletov, E. D.
Maiorova, Russ. Chem. Bull. 1999, 48, 367.
[23] G. Consiglio, S. Failla, P. Finocchiaro, Phosphorus Sulfur Sili-
con Relat. Elem. 1996, 117, 37.
[24] Although the reactions run smoothly with 3 equiv. of arenes
with the same selectivity, to avoid the problems associated with
the solubility of phosphonates and the volatility of liquid aryl-
ating reagents, 3.0–20.0 mol equiv. of arenes were used.
Received: October 12, 2012
1
the range of δ = 6.51–6.60 ppm in the H NMR spectra and at
δ = 48.9 ppm (d, J = 137.8 Hz) in the 13C NMR spectra. The
singlets in the range of δ = 25.0–25.2 ppm in the 31P NMR
spectra indicate the formation of compounds of type 2Ј
(Table 1).[2d] For more substituted compounds (mesitylene and
durene), doublets of doublets appear at δ ≈ 4.55 ppm (J ≈ 32.0
and 6.0 Hz) in the 1H NMR spectra and doublets at δ ≈
44.0 ppm (d, J ≈ 120.0 Hz) in the 13C NMR spectra. In the 31
P
NMR spectra, singlets were observed at δ ≈ 27.0 ppm, which
again supports our observations.
Published Online: ᭿
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O21352
/KAP1
Date: 19-12-12 10:05:39
Pages: 9
Arylation of α-Hydroxyphosphonates
Arylation of α-Hydroxyphosphonates
G. Pallikonda, M. Chakravarty* ....... 1–9
FeCl3-Mediated Arylation of α-Hydroxy-
phosphonates with Unactivated Arenes:
Pseudo-Umpolung in Allylic Phosphonates
Keywords: Synthetic methods / Umpolung /
Allylic compounds / Phosphonates / Ar-
enes / Iron
A facile and solvent-free synthesis of γ-
aryl-substituted vinylphosphonates and di-
ethyl (diarylmethyl)phosphonates has been
developed under mild conditions. The reac-
tion was performed with inexpensive FeCl3
and easily accessible α-hydroxyphosphon-
ates and unactivated arenes. In this atom-
economic approach, hard-to-achieve allyl-
phosphonate cations are stabilized through
extended conjugation.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
9