Arylation of α-substituted diethyl methylphosphonates with π-complexes of haloarenes

Article abstract of DOI:10.1023/A:1015306825816

Nucleophilic aromatic substitution of halogen in neutral and cationic π-complexes of haloarenes η⁶-(ArF)Cr(CO)₃ and [η⁶-(ArHlg)FeCp]⁺[PF₆]^- (Hlg = F, Cl) by carbanions derived from α-substi

Full text of DOI:10.1023/A:1015306825816

Russian Journal of Organic Chemistry, Vol. 38, No. 1, 2002, pp. 76 86. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 1, 2002,
pp. 85 94.
Original Russian Text Copyright
2002 by Artamkina, Sazonov, Beletskaya.
Arylation of -Substituted Diethyl Methylphosphonates
with -Complexes of Haloarenes*
G. A. Artamkina, P. K. Sazonov, and I. P. Beletskaya
Faculty of Chemistry, Moscow State University, Vorob’evy gory, Moscow, 119899 Russia
e-mail: gaa@elorg.chem.msu.ru
Received May 10, 2001
Abstract Nucleophilic aromatic substitution of halogen in neutral and cationic -complexes of haloarenes
6-(ArF)Cr(CO)3 and [ 6-(ArHlg)FeCp]+[PF6] (Hlg = F, Cl) by carbanions derived from -substituted diethyl
methylphosphonates [CHZP(O)(OEt)2] (Z = CN, COOEt), generated in situ by the action of Cs2CO3, leads
to formation of the corresponding arylmethylphosphonate complexes in 78 88% yield. The reaction of the
complexes [ 6-{ArCHZP(O)(OEt)2}FeCp]+ [PF6] with 1,10-phenanthroline in acetonitrile on exposure to
daylight yields 32 44% of the free diethyl arylmethylphosphonates.
Reactions of aryl and hetaryl halides with stabilized
carbanions containing an -phosphinoyl group in
addition to other electron-acceptor substituents lead
to formation of new functionally substituted organic
phosphonates and diphosphonates. Such compounds
attract interest as potential biologically active sub-
stances and new synthons for preparation of aryl- or
hetaryl-substituted alkenes by the Horner Emmons
reaction.
attack involves -coordination of the aromatic sub-
strate to transition metals. This approach was success-
fully utilized in the arylation of a number of stabilized
carbanions derived from -dicarbonyl compounds
[4 6], including diethyl malonate derivatives [7, 8];
here, haloarene complexes with cyclopentadienyliron
cation were used as arylating agents.
In the present work we studied the possibility for
arylation with neutral and cationic haloarene -com-
plexes 6-(ArHlg)Cr(CO)3 and [ 6-(ArHlg)FeCp]+
[PF6] of substituted diethyl methylphosphonates of
the general formula ZCH2P(O)(OEt)2 (I III) where
Z is an additional electron-acceptor group [I, Z =
COOEt; II, Z = CN; III, Z = P(O)(OEt)2]. Preliminary
experiments showed that ethyl diethoxyphosphinoyl
acetate (I) smoothly reacts with p-nitrofluorobenzene
in DMF at room temperature in the presence of CsF
or Cs2CO3 as a base. After 3.5 h, the corresponding
arylation product was formed in 83% yield (according
to the 31P NMR data); the yield of the isolated product
was 70% (by chromatography on silica gel). Likewise,
p-nitrofluorobenzene readily reacted with diethyl
cyanomethylphosphonate (II). These results led us to
expect successful arylation with haloarene complexes
of transition metals.
In the preceding communication [1] we reported on
the arylation of carbanions derived from -substituted
dialkyl methylphosphonates with fairly electrophilic
haloarenes, perfluoro- and perchloroaromatic com-
pounds. Arylation of stabilized carbanions with non-
activated haloarenes presents a considerably more
difficult problem. A known way for solving this
problem is based on catalytic cross-coupling, e.g.,
arylation of -phosphinoyl carbanions of the general
formula [CHZP(O)(OEt)2] (Z = CN, SO2R, COOEt)
in the presence of an equivalent amount of CuI, which
requires fairly severe conditions (DMF or HMPA,
100 C) [2]. Sakamoto et al. [3] reported on the only
example of Pd(PPh3)4-catalyzed arylation of diethyl
cyanomethylphosphonate (DME, 85 C). Another
general way of activating haloarenes to nucleophilic
____________
However, ester I failed to react with the tricar-
bonylchromium complex of p-chlorotoluene (IV-Cl)
in the system DMF Cs2CO3. No reaction was also
observed with preliminarily prepared sodium salt of I,
NaCH(COOEt)P(O)(OEt)2. On prolonged heating
(30 h at 60 C) in the presence of 18-crown-6, the
*
This study was financially supported by the Russian Founda-
tion for Basic Research (projects nos. 98-03-32973a and 00-
15-97406) and by the Federal Program State Support of
the Integration of Higher Education and Basic Research
(project no. AO 115).
1070-4280/02/3801-0076$27.00 2002 MAIK Nauka/Interperiodica

ARYLATION OF -SUBSTITUTED DIETHYL METHYLPHOSPHONATES
77
conversion of the initial compound was as low as
Scheme 1.
10%. The reaction of phosphonate II sodium salt
NaCH(CN)P(O)(OEt)2 with complex IV-Cl was much
faster, and the corresponding product was obtained
in 75% yield* in 1.5 2 h. Obviously, for the arylation
to be successful it is necessary to enhance electro-
philicity of the aromatic substrate in one or another
way. For example, the higher mobility of fluorine
atom as compared to chlorine in arene(tricarbonyl)-
chromium complexes can be utilized [9 11].
Both CH acids reacted with fluorobenzene tricar-
bonylchromium complex IV-F even at room tempera-
ture in the presence of Cs2CO3 as a base (runs. nos. 1
and 2; Table 1). Tetrahydrofuran can be used as sol-
vent in the reaction with cyanomethylphosphonate II,
which facilitates isolation of the product. According
to the TLC data, the reactions are sufficiently fast
(in 2 h, the conversion is more than 50%), and only
small amounts of by-products are formed. However,
the conversion of initial fluorobezene complex IV-F
is not complete; after 48 h, it remains in the reaction
mixture even in the presence of excess (5 10%) CH
acid. The products, tricarbonylchromium complexes
of benzylphosphonates V and VI (Scheme 1), were
isolated in good yields (77 80%) and were charac-
V, Z = CN; VI, Z = COOEt.
Therefore, we tried haloarene complexes with cyclo-
pentadienyliron cation as arylating agents toward sub-
stituted dialkyl methylphosphonates ZCH2P(O)(OEt)2
[Z = COOEt, CN, P(O)(OEt)2].
Cationic complexes of cyclopentadienyliron with
chlorobenzene (IXa), p-dichlorobenzene (IXb), and
p-fluorotoluene (IXc) smoothly reacted with phospho-
nates I and II in the presence of excess Cs2CO3 as
a base (20 C; for the other conditions, see Table 3).
The progress of the reaction can be monitored by
31P NMR spectroscopy: signals of the initial CH acids
disappear, and those belonging to deprotonated form
A of the product appear. After acidification, signals
from arylated CH acids X and XI are observed in the
spectrum. No by-products were detected. An intense
red color develops as the reaction progresses. The
corresponding absorption band of complex A in the
1
terized by H and 13C NMR spectra (Tables 1, 2).
Complexes V and VI are very sensitive to oxidation;
on exposure to air they are converted into phospho-
nates VIIa and VIIIa. Preparative oxidation of V
and VI with excess molecular iodine [11] gave com-
pounds VIIa and VIIIa in 90% yield (70% after
chromatographic purification). However, the applica-
tion of fluoroarene tricarbonylchromium complexes
as arylating agents is strongly limited by difficulties
in the preparation of such complexes (especially of
those with fluoroarenes containing acceptor substit-
uents) and their high lability. It is well known that
coordination of an aromatic substrate to the cationic
visible region (
= 442 452 nm) was also used
max
to monitor the reaction course. The reaction was
assumed to be complete when the optical density no
longer increased. Cationic benzylphosphonate com-
plexes Xa Xc and XIa XIc (Scheme 2) were isolated
in good yields (78 88%) by acidification and addition
of excess NaPF6. They were characterized by 1H NMR
spectra (Table 3) and analytical data.
As well as in the previously studied reactions with
polyfluoroaromatic compounds [1] or fluorobenzene
tricarbonylchromium complex, cyanomethylphospho-
nate II turned out to be more reactive than phos-
phinoylacetate I. The reactions with phosphonate II
occur at a sufficient rate in solvents which are less
polar than DMF, e.g., in THF or acetonitrile. Phos-
phonate II also reacts with chlorobenzene complex
IXa without a solvent, on intermittent grinding with
a glass rod of a paste-like mixture of the reactants
with Cs2CO3, but the process is not complete in 24 h
(unlike the reaction in THF; run no. 3, Table 3). It
should be noted that the higher reactivity of stronger
+
species [C5H5Fe] considerably enhances electro-
philicity of the former, as compared with neutral tri-
carbonylchromium complexes [9, 10, 12]. The com-
plexes [ 6-(ArHlg)FeCp]+ [PF6] are fairly resistant to
oxidation (see, e.g., [12, 13]). They can be synthesized
in one step from accessible starting compounds
[12, 14], and hence they are free from disadvantages
intrinsic to the tricarbonylchromium complexes. In
keeping with some published data [9, 10, 12], the
activity of such complexes in SNAr reactions is com-
parable with the activity of 2,4-dinitrochlorobenzene.
____________
*
The yield was calculated taking into account that only 50% of
the initial CH acid can be consumed in the reaction because
of subsequent transmetalation.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

78
ARTAMKINA et al.
Scheme 2.
IX XI, X = H, Hlg = Cl (a); X = Hlg = Cl (b); X = CH3, Hlg = F (c); X, Z = CN; XI, Z = COOEt.
CH acid II is consistent with the mechanism involv-
ing proton transfer in the rate-determining stage.
which leads to formation of diethyl fluorophosphate
and (Ar2CZ)Cs (an analogous process was studied by
us in detail previously [1]). Obviously, the arylation
of phosphonates ZCH2P(O)(OEt)2 in the presence of
fluoride ions should not be carried out at elevated
temperature.
The structure of colored complex A is an interest-
ing point. Such complexes are usually represented in
the form of canonical zwitterionic and neutral species
A1 and A2 (Scheme 3). However, the question so as to
whether this complex exists as an individual species
or as an adduct with inorganic ion (Cs+, Cl , [PF6] )
was not discussed [5, 7]. We have found that the
signal from [PF6] ion decreases in intensity as the
reaction progresses and that it disappears almost com-
pletely by the end of the process. Presumably, [PF6]
ions leave the solution as the salt CsPF6; therefore,
addition of a hexafluorophosphate(V) salt is quite
necessary for isolation of final products X and XI.
Furthermore, addition of hydrochloric acid to the
p-Fluorotoluene complex IXc is more reactive than
chloroarene complexes, but the difference is relatively
small. According to published data, the presence of
a positive charge in complexes like IX levels the
effect of the ring substituent, as well as the element
effect (F/Cl) [10].
Cesium fluoride as a base was much less efficient
than Cs2CO3. In the reactions of complex IXa with
both CH acids I and II in the system THF CsF
(2.5 3 equiv) and even in the system THF DMF
(1:1) CsF, the conversion was as low as <5%. Better
results were obtained when the reaction was carried
out in DMF: the yield of the arylation product attains
40% from cyanomethylphosphonate II and 20% from
ester I (20 C, 6 8 h). On heating the reaction mixtures
for 6 8 h at 80 C, signals belonging to the arylation
product disappear from the 31P NMR spectrum, pre-
sumably because of further reaction with fluoride ion,
Table 1. Reactions of ethyl diethylphosphinoylacetate (I) and diethyl cyanomethylphosphonate (II) with fluorobenzene
tricarbonylchromium complex IV-F in the presence of 3 equiv of Cs2CO3; 20 C
Run
no.
Yield,
%
Z
Reaction conditions
THF, 48 h
Product
1H NMR spectrum (acetone-d6, 20 C), , ppm
1
2
CN
V
80
77
1.299 t, 1.310 t (6H, CH3); 4.17 4.25 m (4H, CH2);
4.820 d (1H, CH, JH, P = 26 Hz); 5.64 5.80 (5H,
C6H5)
1.253 t, 1.259 t (6H, POCH2CH3); 1.298 t (3H,
COCH2CH3); 4.06 4.16 m (4H, POCH2CH3),
4.132 d (1H, PCH, JH, P = 24 Hz); 4.232 q (2H,
COCH2CH3); 5.574 t, 5.630 t, 5.684 t (3H, m-H,
p-H); 5.796 (1H, o-H), 6.232 (1H, o-H)
COOEt
DMF, 48 h
VI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

ARYLATION OF -SUBSTITUTED DIETHYL METHYLPHOSPHONATES
79
Table 2. 13C NMR spectra of -substituted benzylphosphonates V, VIIa, and VIIIa
Compound
Chemical shifts C, ppm
6-[C6H5CH(CN)P(O)(OEt)2]Cr(CO)3 (V) 16.55 d (CH3, JC, P = 5.5 Hz); 36.29 d (CH, JC, P = 133 Hz); 65.12 d
(CH2, JC, P = 7 Hz); 65.25 d (CH2, JC, P = 7 Hz); 93.03 d (Co, JC, P
2.5 Hz); 93.94, 94.10, 94.20 (Cm, Cp); 96.08 d (Co, JC, P
=
=
2 Hz); 101.40 d (Ci, JC, P = 4.5 Hz); 114.82 d (CH, JC, P = 10 Hz),
233.10 (CO)
C6H5CH(CN)P(O)(OEt)2 (VIIa)
16.48 t (CH3, JC, P = 5 Hz); 36.52 d (CH, JC, P = 137 Hz); 64.62 ta (CH2,
JC, P = 7 Hz); 116.86 d (CN, JC, P = 10 Hz); 129.28 d (Cp, JC, P
=
3 Hz); 129.63 d (Cm, JC, P = 3 Hz); 129.70 d (Co, JC, P = 5 Hz);
129.93 d (Ci, JC, P = 8 Hz)
C6H5CH(COOEt)P(O)(OEt)2 (VIIIa)
14.32 (COCH2CH3); 16.47 d (POCH2CH3, JC, P = 6 Hz); 16.62 d (POCH2-
CH3, JC, P = 6 Hz); 52.48 d (CHP, JC, P = 133 Hz); 61.98 (COCH2CH3);
63.22 d (POCH2CH3, JC, P = 6.5 Hz); 63.45 d (POCH2CH3, JC, P
=
6.5 Hz); 128.41 d (Cp, JC, P = 2.5 Hz); 128.92 d (Cm, JC, P = 2.5 Hz);
130.68 d (Co, JC, P = 6.5 Hz); 132.64 d (Ci, JC, P = 8.5 Hz),
168.18 (CO, JC, P = 3.5 Hz)
a
Superposition of two doublets.
reaction mixture (after filtration) leads to almost
quantitative precipitation of CsCl. These findings may
be explained on the assumption that complex A in
the reaction mixture exists in the form of an adduct
with CsCl (CsF). Thus zwitterionic structure A1 is
more appropriate for such complexes in solution.
energy barrier to nucleofuge elimination is typical
of nucleophilic replacement in haloarenes activated
through -coordination with transition metals, espe-
cially in the case of cationic complexes [10].
Let us consider briefly one interesting feature of
1
the H and 13C NMR spectra of complexes X and
The formation of nucleophilic substitution products
as deprotonated species A is readily explainable:
cationic complexes X and XI should be very strong
CH acids; therefore, they should readily lose a proton
by the action of Cs2CO3. However, it is more probable
that proton abstraction occurs at the stage of formation
of the corresponding -complex, thus facilitating
elimination of halide ion; in other words, complex A
is formed directly from the -complex via -elimina-
tion of hydrogen halide (Scheme 4). This reaction
path seems to be preferred to elimination of anionic
species (Hlg ) from the neutral complex, which is
unfavorable at least for electrostatic reasons. Elimina-
tion of nucleofuge from the endo-position of such
-complexes may also be hindered for steric reasons
[10]. According to published data, a relatively high
XI. Protons in the ortho- and meta-positions of the
aromatic ring are magnetically nonequivalent, as well
as the corresponding protons and carbon nuclei in tri-
carbonylchromium complexes V and VI (Tables 1 3).
1
The aromatic region of the H NMR spectra of para-
substituted complexes displays a superposition of two
AB systems. Sutherland and co-workers [8] described
an analogous nonequivalence of the two ethoxycar-
bonyl groups in complexes of meta- and ortho-sub-
stituted aralalkylmalonic acid esters with the [CpFe]+
cation. The authors erroneously explained the ob-
served pattern by restricted rotation about the Ar C
bond. In fact, this is the result of chiral structure of
metal complexes with arenes having at least two dif-
ferent substituents in the meta- or orto-positions [15].
In our case, molecules V, VI, X, and XI already have
Scheme 3.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

80
ARTAMKINA et al.
Table 3. Reactions of ethyl diethoxyphosphinoylacetate (I), diethyl cyanomethylphosphonate (II), and tetraethyl
methylenediphosphonate (III) with complexes [CpFeArHal]+ [PF6] (IXa IXc) in the presence of Cs2CO3 (3 equiv); 20 C
NMR spectra of X and XI,a , ppm
Run
no. complex
Initial
Reaction
conditions
Yield,
%
Z
Product
b
(acetone-d6, 20 C)
H
P
1
2
3
IXa
IXa
CN
DMF, 1 h
THF, 24 h
No solvent, 24 h
Xa
Xa
Xa
80
78
65
26.1
26.3
1.269 t, 1.282 t (6H, CH3); 4.15 4.26 m
(4H, CH2); 5.326 d (1H, CHP, JH, P
=
25 Hz); 5.335 s (5H, C5H5); 6.59
6.75 m (5H, C6H5)
4
COOEt
DMF, 5 h
XIa
81
30.1
1.224 t, 1.237
1.395 t (3H, COCH2CH3); 4.109 m
(4H, POCH2CH3); 4.431 (2H,
COCH2CH3); 4.788 (1H, CHP,
t (6H, POCH2CH3);
q
d
JH, P = 24 Hz); 5.157 s (5H, C5H5);
6.57 m (4H); 6.86 (1H) (C6H5)
5
6
IXb
IXb
CN
CH3CN, 9 h
THF, 24 h
Xb
Xb
88
25.5
26.4
1.275 t, 1.289 t (6H, CH3); 4.16 4.25 m
55c
(4H, CH2); 5.313 d (1H, CHP, JH, P =
25 Hz); 5.450 s (5H, C5H5); 6.753 td
(2H), 7.001 d (1H), 7.038 (1H) (C6H4)
7
COOEt
DMF, 20 h
XIb
84
29.0
1.230 t, 1.246
1.376 t (3H, COCH2CH3); 4.115 m
(4H, POCH2CH3); 4.402 (2H,
COCH2CH3); 4.817 (1H, CHP,
t (6H, POCH2CH3);
q
d
JH, P = 24 Hz); 5.258 s (5H, C5H5);
6.682 d (1H); 6.91 6.94 m, 6.969 d
(3H) (C6H4)
8
9
IXc
IXc
CN
THF, 3 h
Xc
78
83
26.2
30.3
1.270 t, 1.285
t (6H, POCH2CH3);
2.613 s (3H, ArCH3); 4.15 4.23 m
(4H, CH2); 5.288 d (1H, CHP, JH, P
=
25 Hz); 5.285 s (5H, C5H5); 6.543 me
(2H); 6.578 q (2H, C6H4, AB system,
JA, B = 6.8 Hz)
COOEt
CH3CN, 24 h
XIc
1.228 t, 1.237
1.385 t (3H, COCH2CH3); 2.577 s
(3H, ArCH3); 4.06 4.14 (4H,
t (6H, POCH2CH3);
m
POCH2CH3); 4.417 q (2H, COCH2);
4.746 d (1H, CHP, JH, P = 24 Hz),
5.095 s (5H, C5H5); 6.46 6.50 m
(3H); 6.780 d (1H, J = 6.7 Hz) (C6H4)
1.275 t, 1.328 t (12H, POCH2CH3);
4.05 4.29 m (8H, POCH2CH3); 4.371 t
(1H, CHP, JH, P = 24 Hz), 5.28 s (5H,
C5H5); 6.563 br.s (5H, C6H5)
10
IXa
P(O)(OEt)2 DMF, 72 hf
XII
60
29.2
a
31P NMR spectrum of the [PF6] ion and initial compounds, 20 C, P, ppm (solvent): [PF6] , 143.9 (THF), 144.3 (DMF);
CH2(CN)P(O)(OEt)2, 15.8 (THF); CH2(COOEt)P(O)(OEt)2, 19.5 (DMF); CH2[P(O)(OEt)2]2, 19.7 (DMF).
31P {1H} NMR spectrum of deprotonated form A of complexes X and XI in the same solvent as that used as reaction medium; 20 C.
Conversion 75%.
Superposition of two doublets.
Unresolved AB-quartet.
b
c
d
e
f
The reaction was performed with 2 equiv of preliminarily prepared NaCH[P(O)(OEt)2]2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

ARYLATION OF -SUBSTITUTED DIETHYL METHYLPHOSPHONATES
81
Scheme 4.
*
an asymmetric carbon atom [ArCHZP(O)(OEt)2], so
that usually equivalent ortho- and meta-positions of
the aromatic ring become diastereotopic [16].
occur, but it does not lead to formation of arylation
product.
The sodium salt NaCH[P(O)(OEt)2]2, prepared
from phosphonate III by the action of NaH, slowly
reacts with chlorobenzene complex IXa in DMF
following Scheme 5. According to the 31P NMR
data, the reaction with 2 equiv of NaCH[P(O)(OEt)2]2
at a concentration of 0.5 M proceeds by 75% in 18 h
at 20 C. On further increase of the reaction time,
the signal from complex A in the 31P NMR spectrum
no longer increases but begins to decrease. At the
Our attempts to effect arylation of tetraethyl
methylenediphosphonate (III) with cationic haloarene
complexes under conditions of phase-transfer catalysis
were unsuccessful. The reaction of bis-phosphonate
III with p-fluorotoluene complex IXc in the presence
of Cs2CO3 (CH3CN, 20 C, 15 h) gave no arylation
product. The 31P NMR spectrum of the reaction mix-
ture contained only the signal from the initial CH
acid. Under more severe conditions (DMF, 60 C, 4 h),
the yield of the arylation product did not exceed 6%
(if it was formed). On the other hand, in the two cases
the reaction mixture quickly turned crimson, and the
same time, the intensity of the signal at
20 ppm,
P
which belongs to free CH acid III or its mixture with
unidentified by-products, continuously increases (up
to 65% of the overall signal intensity). In addition,
broadening of the 31P signals from phosphinoyl
groups is observed. The desired product, cationic aryl-
methylenediphosphonate complex XII, was isolated
in 60% yield by appropriate treatment of the reaction
absorption maximum (
= 540 nm) was located
at longer wavelengths than those typical of type A
max
complexes. The [PF6] signal disappeared from the
31P NMR spectrum, and the H NMR spectrum (in
1
1
CH3CN) lacked a characteristic singlet from cyclo-
pentadienyl fragment. These findings indicate that
some reaction involving initial haloarene IXc does
mixture, and its H NMR spectrum was recorded (run
no. 10; Table 3). Strangely enough, carbanion of the
weakest CH acid III (pKa 23; calculated by the
Scheme 5.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

82
ARTAMKINA et al.
Scheme 6.
VII, X, Z = CN; VIII, XI, Z = COOEt; o-Phen = 1,10-phenanthroline.
Kabachnik equation [17]) turned out to be the least
nucleophilic in the series under study. This may be
due to strong association of its salts in solution.
increases. Most arylmethylphosphonates VII and VIII
were reported previously (see, e.g., [2, 3]) and were
1
identified by the H NMR spectra (Table 4) and 13C
NMR spectra (for VIIa and VIIIa; Table 2). Newly
synthesized compounds VIIIb and VIIIc were addi-
tionally characterized by elemental analysis.
An important aspect of using the above reactions
as a method of arylation of substituted methylphos-
phonates is transformation of the resulting complexes
X and XI into free arylmethylphosphonates. A number
of procedures were proposed for liberation of arene
ligands from their complexes with cyclopentadienyl-
iron cation. These include photolysis in a donor
solvent, e.g., acetonitrile [6, 18], vacuum pyrolysis
[5, 7], reaction with 1,10-phenanthroline in daylight
[18, 19], and treatment with sodium tert-butoxide
[19]. The latter procedure is efficient even in the case
of sterically hindered arene ligands but is totally
inapplicable to complexes with arylmethylphospho-
nates. The latter, as strong CH acids, will react with
t-BuONa to give less electrophilic neutral type A
comlexes through elimination of proton. The reaction
with t-BuONa can also involve ester and CH moieties
which are sensitive to bases.
EXPERIMENTAL
1
The H (400 MHz), 31P (161.90 MHz), and 13C
(100.58 MHz) NMR spectra were recorded on
a Varian VXR-400 spectrometer. The 31P NMR spe-
ctra were also measured on a Varian FT-80A instru-
ment operating at 32.4 MHz. The 31P chemical shifts
were measured relative to 85% H3PO4 as external
reference. The electron absorption spectra in the
visible region were recorded on a Hewlett Packard
8452A spectrophotometer.
Cesium carbonate and fluoride were dried for 2 4 h
at 100 180 C under reduced pressure over P2O5.
Dimethylformamide, tetrahydrofuran, and acetonitrile
were dried and purified by standard procedures;
THF was stored over potassium diphenylketyl.
-Complexes IX of haloarenes with cyclopentadienyl-
iron cation were synthesized by reaction of ferrocene
with the corresponding haloarenes in the presence
of AlCl3 and powdered aluminum [12, 14] and were
purified by reprecipitation from acetone with excess
diethyl ether. Complexes IXb and IXc were addi-
tionally recrystallized from acetone benzene. Tri-
carbonylchromium complexes of haloarenes and sub-
stituted methylphosphonates I III were synthesized
by known methods. Their physical properties were
in agreement with published data.
The most widely used procedure for isolation of
arylation products of stabilized carbanions (such as
malonates and other -dicarbonyl compounds) from
their complexes with [CpFe]+ is vacuum pyrolysis
which usually occurs at 200 220 C (0.1 1 mm)
[5, 7]. In fact, by vacuum pyrolysis of the complexes
[
6-Ar{CH(CN)P(O)(OEt)2}FeCp]+[PF6] (X) we
obtained the corresponding arylmethylphosphonates
VII, but their yields were poor (10 20%). Moreover,
a number of by-products were formed, some of which
could not be separated by column chromatography.
We succeeded in isolating the whole series of phos-
phonates VII and VIII, though in moderate yields
(32 44%), by an alternative procedure, namely by
treatment of complexes X and XI with 1,10-phen-
anthroline under day(sun)light (Scheme 6). It should
be noted that decomposition of the complexes was not
quantitative. According to the electron absorption
spectra in the visible region, the concentration of
phenathroline iron complex [Fe(o-Phen)3]2+ reaches
70% of the theoretically possible one, and it no longer
Reaction of substituted diethyl methylphospho-
nates with haloarene -complexes under conditions
of phase-transfer catalysis (general procedure).
A flat-bottom Schlenk vessel was charged with pre-
liminarily dried powdered CsF or Cs2CO3 and was
evacuated for 0.5 h at 180 C. Haloarene complex, CH
acid (usually in 5 15% excess), and DMF were added
in succession under counterstream of argon, and the
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ARYLATION OF -SUBSTITUTED DIETHYL METHYLPHOSPHONATES
83
Table 4. Reactions of the complexes [CpFeArCH(Z)P(O)(OEt)2]+ [PF6] (X and XI) with 1,10-phenanthroline (3 equiv)
in daylight; CH3CN, concentration of X and XI 0.02 0.035 M, 20 C
Initial complex
Yield,
Product
VIIa
1H NMR spectrum (acetone-d6, 20 C), , ppm
%
no.
X
Z
Xa
H
CN
32
1.213 t, 1.243 t (6H, CH3); 3.96 4.15 m (4H, CH2); 4.903 d (1H,
CHP, JH, P = 26.5 Hz); 7.37 7.47 m (3H, m-H, p-H); 7.49 7.54 m
(2H, o-H)
XIa
H
COOEt
VIIIa
43
1.107 t (3H, COCH2CH3); 1.229 t, 1.234 t (6H, POCH2CH3); 3.83
4.24 m (6H, CH2); 4.360 d (1H, CHP, JH, P = 24 Hz); 7.23 7.37 m
(3H, m-H, p-H); 7.56 7.60 m (2H, o-H)
Xb
Cl
Cl
CN
VIIb
44
40
1.239 t, 1.257 t (6H, CH3); 4.00 4.19 m (4H, CH2); 4.961 d (1H,
CHP, JH, P = 26.5 Hz); 7.48 7.54 m (5H, C6H4)
1.128 t (3H, COCH2CH3); 1.235 t, 1.242 t (6H, POCH2CH3); 3.87
4.23 m (6H, CH2); 4.425 d (1H, CHP, JH, P = 24 Hz); 7.386 d
(2H), 7.599 d (2H, C6H4)
XIb
COOEt
VIIIb
Xc
CH3
CH3
CN
VIIc
42
36
1.216 t, 1.248 t (6H, POCH2CH3); 2.332 s (3H, ArCH3); 3.97
4.15 m (4H, CH2); 4.838 d (1H, CHP, JH, P = 26.5 Hz); 7.249 d
(2H), 7.382 d.q (2H, C6H4, Jq = 2.3 Hz)
1.119 t (3H, COCH2CH3); 1.223 t, 1.230 t (6H, POCH2CH3);
2.299 d (3H, ArCH3, J = 2 Hz); 3.84 4.22 m (6H, CH2); 4.293 d
(1H, CHP, JH, P = 23.5 Hz); 7.152 d (2H), 7.445 d.q (2H,
C6H4, Jq = 2.3 Hz)
XIc
COOEt
VIIIc
mixture was evacuated. When the reaction was carried
out in THF or acetonitrile, the solvent was recon-
densed through a vacuum line. The mixture was
agitated using a magnetic stirrer under argon with
protection from direct daylight, for ( 6-arene)(cyclo-
pentadienyl)iron(II) complexes are very sensitive to
light [12]. When the reaction was performed without
a solvent, the paste-like mixture was intermittently
ground with a glass rod. The conditions are given in
Tables 1 and 3. The progress of the reactions was
monitored by spectrophotometry. For this purpose,
0.02-ml samples were withdrawn and diluted with
500 1250 volumes of acetone, and absorption spec-
trum of the resulting solution was recorded imme-
diately. When the reaction was complete, a part of
the mixture was transferred into an NMR ampule,
the ampule was sealed, and 31P NMR spectrum was
recorded. To monitor the reaction course by 31P NMR
spectroscopy, the reaction was carried out directly in
reservoirs which were connected through a tube with
a built-in glass filter. One reservoir had a side arm
separated by a constriction, and an NMR ampule was
built in the second reservoir. The latter was charged
with initial haloarene -complex ( 0.5 mmol), and the
first reservoir (with a side arm) was charged with
1.5 2 equiv of NaH as a 60% suspension in mineral
oil. The setup was evacuated, and tetrahydrofuran was
recondensed therein to remove mineral oil from NaH.
The solution was collected in the side arm which was
then sealed off. The solvent was evaporated, the setup
was filled with argon, 1.5 2 ml of argon-saturated
DMF was added to sodium hydride, 1 equiv of ap-
propriate CH acid was then added, and the mixture
instantaneously foamed. It was stirred with a magnetic
stirrer with intermittent evacuation until hydrogen
no longer evolved (30 40 min), and the resulting
colorless solution of CH acid sodium salt was filtered
into the second reservoir containing haloarene -com-
an NMR ampule which was charged with the reactants plex; the complex dissolved completely. A part of
and solvent in the same order as above; after evacua- the solution was placed into the built-in NMR ampule,
tion, the ampule was sealed. In this case, the mixture
was stirred by fixing the ampule at a rotor shaft.
Reactions of haloarene -complexes with sub-
stituted methylphosphonate sodium salts. The reac-
tions were carried out in a device consisting of two
the latter was sealed off, and 31P NMR spectrum was
recorded when necessary.
Isolation of ( 6-diethyl arylmethylphosphonate)-
(
5-cyclopentadienyl)iron(II) hexafluorophos-
phates(V). The reaction mixture was filtered through
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

84
ARTAMKINA et al.
Celite into 0.2 0.4 ml of concentrated hydrochloric
acid, the originally bright red filtrate instantaneously
turned pale yellow, and a colorless solid (CsCl)
precipitated. The filter was repeatedly washed with
acetone, and the solution was separated from the CsCl
precipitate by decanting, concentrated to a volume of
1 3 ml, and poured into an aqueous solution of NaPF6
(1.5 2 equiv). A brown yellow oily liquid separated.
The aqueous phase was extracted with 3 portions of
methylene chloride, the extracts were compbined with
the oily substance, and the mixture was evaporated
to dryness on a rotary evaporator. The residue was
dissolved in 2 4 ml of acetone, the solution was
diluted with a 10 15-fold amount of diethyl ether, and
the product, [ 6-Ar{CH(Z)P(O)(OEt)2}FeCp]+ [PF6]
[Z = CN, COOEt, P(O)(OEt)2], was isolated as
a brown yellow oily liquid which foamed on evacua-
tion and solidified to form a pale yellow foam-like
phosphonate II, 400 mg of complex IXc, and 1.12 g
of Cs2CO3 in 1.5 ml of tetrahydrofuran. Yield 430 mg
(77%). Found, %: C 40.24; H 4.17; P 11.52.
C18H23F6FeNO3P2. Calculated, %: C 40.55; H 4.35;
P 11.62.
[
6-Ethyl diethoxyphosphinoyl(p-tolyl)acetate]-
5-cyclopentadienyl)iron(II) hexafluorophos-
(
phate(V) (XIc) was synthesized from 245 mg of
phosphonate I, 385 mg of complex IXc, and 1.2 g
of Cs2CO3 in 1 ml of acetonitrile. Yield 460 mg
(78%). Found, %: C 40.76; H 5.01. C20H28F6FeO5P2.
Calculated, %: C 41.40; H 4.86.
5
[
6-Tetraethyl benzylidenediphosphonate)(
-
cyclopentadienyl)iron(II) hexafluorophosphate(V)
(XII) was synthesized from 125 mg of bis-phospho-
nate III, 82 mg of complex IXa, and 30 mg of NaH
in 1 ml of DMF. Yield 81 mg (60%). Found, %:
C 38.04; H 4.79. C20H31F6FeO6P3. Calculated, %:
C 38.12; H 4.96.
1
material. The H and 31P NMR spectra of the com-
plexes are given in Table 3.
Isolation of ( 6-diethyl arylmethylphosphonate)-
tricarbonylchromium(0) complexes. Excess hydro-
chloric acid was added to the reaction mixture, the
product was extracted into diethyl ether, the extract
was washed with water and evaporated to dryness on
a rotary evaporator, and the residue was subjected to
column chromatography on silica gel L (40/100 m).
Unchanged ( 6-fluorobenzene)tricarbonylchromuim(0)
was eluted with methylene chloride petroleum ether
ethyl acetate (5:10:1); a number of unidentified
products were eluted by gradually increasing the frac-
tion of ethyl acetate in the eluent; and the major frac-
tion was collected when the fraction of ethyl acetate
in the eluent attained 20 30%. The NMR spectra of
the products are given in Tables 1 and 2.
(
6-Diethyl -cyanobenzylphosphonate)( 5-cy-
clopentadienyl)iron(II) hexafluorophosphate(V)
(Xa) was synthesized from 180 mg of phosphonate II,
375 mg of complex IXa, and 1.1 g of Cs2CO3 in
1.5 ml of THF. Yield 400 mg (78%). Found, %:
C 38.91; H 3.87; P 12.01. C17H21F6FeNO3P2. Calcu-
lated, %: C 39.33; H 4.08; P 11.93.
[
6-Ethyl diethoxyphosphinoyl(phenyl)acetate]-
5-cyclopentadienyl)iron(II) hexafluorophos-
(
phate(V) (XIa) was synthesized from 350 mg of
phosphonate I, 568 mg of complex IXa, and 1.46 g
of Cs2CO3 in 1.6 ml of DMF. Yield 690 mg (81%).
Found, %: C 40.16; H 4.51; P 10.70. C19H26F6FeO5P2.
Calculated, %: C 40.31; H 4.63; P 10.94.
(
6-Diethyl p-chloro- -cyanobenzylphospho-
(
6-Diethyl -cyanobenzylphosphonate)tricar-
nate)( 5-cyclopentadienyl)iron(II) hexafluorophos-
phate(V) (Xb) was synthesized from 235 mg of
phosphonate II, 520 mg of complex IXb, and 1.2 g
of Cs2CO3 in 2 ml of acetonitrile. Yield 610 mg
(88%). Found, %: C 36.91; H 3.36; P 11.18.
C17H20ClF6FeNO3P2. Calculated, %: C 36.88; H 3.64;
P 11.19.
bonylchromium(0) (V) was synthesized from 190 mg
of phosphonate II, 220 mg of complex III-F, and
0.95 g of Cs2CO3 in 2 ml of tetrahydrofuran. Yield
295 mg (80%).
[
6-Ethyl diethoxyphosphinoyl(phenyl)acetate]-
tricarbonylchromium(0) (VI) was synthesized from
250 mg of phosphonate I, 260 mg of complex III-F,
and 1.1 g of Cs2CO3 in 1.6 ml of dimethylformamide.
Yield 375 mg (77%).
[
6-Ethyl p-chlorophenyl(diethoxyphosphinoyl)-
acetate]( 5-cyclopentadienyl)iron(II) hexafluoro-
phosphate(V) (XIb) was synthesized from 240 mg
of phosphonate I, 415 mg of complex IXb, and 1.05 g
of Cs2CO3 in 1.3 ml of DMF. Yield 510 mg (84%).
Found, %: C 38.36; H 4.21. C19H25ClF6FeO5P2. Cal-
culated, %: C 37.99; H 4.20.
6
Vacuum pyrolysis of ( -diethyl benzylphospho-
nate)( 5-cyclopentadienyl)iron(II) hexafluorophos-
phates(V). A 100 300-mg portion of the complex
was dissolved in 1 3 ml of methylene chloride, and
the solution was carefully evaporated in a vacuum
sublimator in such a way that the residue formed
an even film on the walls. The setup was evacuated to
0.1 mm and was heated to 200 220 C over a period
(
6-Diethyl -cyano-p-methylbenzylphospho-
nate)( 5-cyclopentadienyl)iron(II) hexafluorophos-
phate(V) (Xc) was synthesized from 200 mg of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

ARYLATION OF -SUBSTITUTED DIETHYL METHYLPHOSPHONATES
85
of 2 3 h. The dark sublimate was washed off from
the finger condenser with acetone and was subjected
to chromatography on a 15-cm column charged with
silica gel L (40/100 m). The column was eluted first
with methylene chloride petroleum ether (10:15),
and ethyl acetate was then gradually added to the
eluent. Initially, a number of unidentified products
were washed off from the column. A fraction contain-
ing the major product was collected when the eluent
contained 20 30% of ethyl acetate.
Ethyl p-chlorophenyl(diethoxyphosphinoyl)-
acetate (VIIIb) was synthesized from 340 mg of
complex XIb and 340 mg of 1,10-phenanthroline in
17.5 ml of acetonitrile. Reaction time 7 h. Yield
80 mg (40%). Oily liquid. Found, %: C 50.04; H 6.43;
P 9.49. C14H20ClO5P. Calculated, %: C 50.23; H 6.02;
P 9.25.
Diethyl -cyano-p-methylbenzylphosphonate
(VIIc) [3, 20] was synthesized from 180 mg of com-
plex Xc and 185 mg of 1,10-phenanthroline in 14 ml
of acetonitrile. Reaction time 5 h. Yield 39 mg (42%).
Oily liquid.
Isolation of arylphosphonates by reaction of
(
6-diethyl benzylphosphonate)( 5-cyclopentadi-
Ethyl diethoxyphosphinoyl(p-tolyl)acetate
(VIIIc) was synthesized from 220 mg of complex
XIc and 245 mg of 1,10-phenanthroline in 12 ml of
acetonitrile. Reaction time 7 h. Yield 43 mg (36%).
Oily liquid. Found, %: C 56.84; H 7.54; P 9.65.
C15H23O5P. Calculated, %: C 57.32; H 7.38; P 9.85.
enyl)iron(II) complexes with 1,10-phenanthroline.
A 140 500-mg portion (1 equiv) of appropriate com-
plex and 3 equiv of 1,10-phenanthroline were dis-
solved in acetonitrile to attain an initial complex
concentration of 0.02 0.035 M (at higher concentra-
tions the yield of the product was lower). The solution
was stirred in a glass flask with a magnetic stirrer
on exposure to sunlight. The progress of the reaction
was monitored by electron spectroscopy. A 0.02-ml
sample of the mixture was diluted with a 100-fold
volume of acetone, and the optical density was
measured at the absorption maximum of the iron(II)
complex with 1,10-phenanthroline [Fe(o-Phen)3]2+,
REFERENCES
1. Artamkina, G.A., Tarasenko, E.A., Lukashev, N.V.,
and Beletskaya, I.P., Tetrahedron Lett., 1998, vol. 39,
pp. 901 904; Tarasenko, E.A., Artamkina, G.A.,
Voevodskaya, T.I., Lukashev, N.V., and Belets-
kaya, I.P., Russ. J. Org. Chem., 1998, vol. 34, no. 10,
pp. 1459 1463.
= 508 nm,
11000. After 2.5 4 h, the optical
max
density no longer increased, and an appreciable
amount of a solid separated from the solution. The
mixture was kept for an additional 1 2 h on exposure
to light and evaporated to dryness. The residue was
passed through a short (h = 3 4 cm) column charged
with silica gel L (40/100 m) using chloroform as
eluent. The eluate was shaken with 0.1 0.2 ml of
concentrated hydrochloric acid to remove 1,10-phen-
anthroline and was filtered again through a similar
2. Suzuki, H., Watanabe, K., and Yi, Q., Chem. Lett.,
1985, pp. 1779 1780; Minami, T., Isonaka, T.,
Okada, Y., and Ichikawa, J., J. Org. Chem., 1993,
vol. 58, no. 25, pp. 7009 7015.
3. Sakamoto, T., Katoh, E., Kondo, Y., and Yama-
naka, H., Heterocycles, 1988, vol. 27, no. 6, pp. 1353
1356; Sakamoto, T., Katoh, E., Kondo, Y., and
Yamanaka, H., Chem. Pharm. Bull., 1990, vol. 38,
no. 6, pp. 1513 1517.
1
column (see above). The H and 13C NMR spectra of
4. Moriarty, R.M. and Gill, U.S., Organometallics, 1986,
the products are given in Tables 4 and 2, respectively.
vol. 5, no. 2, pp. 253 256.
Diethyl -cyanobenzylphosphonate (VIIa) [2, 3]
was synthesized from 550 mg of complex Xa and
580 mg of 1,10-phenanthroline in 33 ml of aceto-
nitrile. Reaction time 4.5 h. Yield 85 mg (32%).
Oily liquid.
Ethyl diethoxyphosphinoyl(phenyl)acetate
(VIIIa) [2] was synthesized from 530 mg of complex
XIa and 530 mg of 1,10-phenanthroline in 35 ml of
acetonitrile. Reaction time 4 h. Yield 120 mg (43%).
Oily liquid.
Diethyl p-chloro- -cyanobenzylphosphonate
(VIIb) [20] was synthesized from 145 mg of complex
Xb and 155 mg of 1,10-phenanthroline in 13 ml of
acetonitrile. Reaction time 5 h. Yield 34 mg (44%).
Oily liquid.
5. Abd-El-Aziz, A.S., Lee, C.C., Piorko, A., and Suther-
land, R.G., J. Organomet. Chem., 1988, vol. 348,
pp. 95 107.
6. Abd-El-Aziz, A.S., Boraie, W., Al-Salem, N.,
Sadek, S.A., and Epp, K.M., J. Chem. Soc., Perkin
Trans. 1, 1997, pp. 1469 1479.
7. Abd-El-Aziz, A.S., Lee, C.C., Piorko, A., and Suther-
land, R.G., Synth. Commun., 1988, vol. 18, no. 3,
pp. 291 300.
8. Piorko, A., Abd-El-Aziz, A.S., Lee, C.C., and Suther-
land, R.G., J. Chem. Soc., Perkin Trans. 1, 1989,
pp. 469 475.
9. Nesmeyanov, A.N., Vol’kenau, N.A., Isaeva, L.S.,
and Bolesova, I.N., Dokl. Akad. Nauk SSSR, 1968,
vol. 183, no. 4, pp. 834 837.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002

86
ARTAMKINA et al.
10. Litvak, V.V. and Shteingarts, V.D., Izv. Sib. Otd.
Akad. Nauk SSSR, Ser. Khim., 1983, no. 4,
pp. 59 68.
15. Potapov, V.M., Stereokhimiya (Stereochemistry),
Moscow: Khimiya, 1988, pp. 19, 433.
16. Ustynyuk, Yu.A., Artamkina, G.A., Luzikov, Yu.N.,
Grishin, Yu.K., Azizov, A.A., and Beletskaya, I.P.,
Zh. Org. Khim., 1976, vol. 12, no. 8, pp. 1615 1618.
11. Semmelhack, M.F. and Hall, H.T., J. Am. Chem.
Soc., 1974, vol. 96, pp. 7091 7092.
17. Kabachnik, M.I. and Mastryukova, T.A., Russ. J.
Gen. Chem., 1993, vol. 63, no. 1, pp. 1 16.
12. Nikitina, T.V., Metody elementoorganicheskoi khimii
(Methods of Organometallic Chemistry), Nesmeya-
nov, A.N. and Kocheshkov, K.A., Eds., Moscow:
Nauka, 1985, pp. 371 384.
18. Pearson, A.J., Gelormini, A.M., Fox, M.A., and
Natrins, D., J. Org. Chem., 1996, vol. 61, no. 4,
pp. 1297 1305.
13. Storm, J.P. and Andersson, C.-M., J. Org. Chem.,
2000, vol. 65, no. 17, pp. 5264 5274.
19. Brown, R.A., Fernando, S.I.S., and Roberts, R.M.G.,
J. Chem. Soc., Perkin Trans. 1, 1994, pp. 197 201.
14. Nesmeyanov, A.N., Vol’kenau, N.A., and Boleso-
va, I.N., Dokl. Akad. Nauk SSSR, 1963, vol. 149,
no. 3, pp. 607 610.
20. Kim, D.Y. and Oh, D.Y., Synth. Commun., 1987,
vol. 17, no. 8, pp. 953 958.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 1 2002