Synthesis of alkyl tetraphosphonates: First example of nickel catalyst for H-phosphonates addition to diynes

Article abstract of DOI:10.1134/S1070428013080010

Efficient algorithm was developed for the analysis of products of the catalytic reaction of diynes multiphosphorylation based on combined application of ³¹P NMR DOSY spectra and HPLC-MS method. Using this analytical approach the reaction of H-phosphonates addition to diynes was investigated and a simple synthetic procedure got alkyl tetraphosphonates preparation was developed.

Full text of DOI:10.1134/S1070428013080010

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 8, pp. 1099−1207. © Pleiades Publishing, Ltd., 2013.
Original English Text © Yu.V. Ivanova, L.L. Khemchyan, S. S. Zalesskii, V.P Ananikov, I.P. Beletskaya, 2013, published in Zhurnal Organicheskoi Khimii, 2013,
Vol. 49, No. 8, pp. 1119−1127.
Dedicated to the memory of Correspondent Member
of the Russian Academy of Sciences M.Yu. Antipin
Synthesis of Alkyl Tetraphosphonates: First Example
of Nickel Catalyst for H-Phosphonates Addition to Diynes
Yu. V. Ivanovaa, L. L. Khemchyana, S. S. Zalesskiia, V. P. Ananikova, and I. P. Beletskayab
aZelinskiy Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, 119991 Russia
e-mail: val@ioc.ac.ru
bLomonosov Moscow State University, Moscow, Russia
Received May 20, 2013
Abstract—Efficient algorithm was developed for the analysis of products of the catalytic reaction of diynes
multiphosphorylation based on combined application of 31P NMR DOSY spectra and HPLC-MS method. Using
this analytical approach the reaction of H-phosphonates addition to diynes was investigated and a simple synthetic
procedure got alkyl tetraphosphonates preparation was developed.
DOI: 10.1134/S1070428013080010
Aspecial attention is directed to the creation of selec-
tive procedures of carbon–phosphorus bond formation
due to the outstanding importance of organophosphorus
compounds in chemistry, medicine, and materials science.
Phosphorus-containing alkene derivatives are biologically
active components [1–5], important compounds for the
chemistry of nucleic acids [6–10], convenient reagents for
a number of synthetic transformations [15–17]. Among
the multiple organophosphorus molecules special atten-
tion is lately drown to vinylphosphonates A that exhibit a
wide range of biologic activity [18–21].
complex catalysis in the recent years advanced a new stage
in the study of the catalytic reactions of the carbon–phos-
phorus bond formation based on acetylene hydrocarbons
thus introducing quite a number of promising routes [34].
In particular, the application of addition of molecules
containing a phosphorus–hydrogen bond to unsaturated
organic compounds catalyzed by the transition metal com-
plexes made it possible to develop a convenient synthetic
method of carbon-phosphorus bonds formation [35–39].
100% atomic efficiency of the addition reaction combined
with a high regioselectivity permitted a development of
economical and environmentally safe synthetic procedures.
R1
R2O
P
The first example of alkynes hydrophosphorylation
catalyzed by transition metal complexes was described
under 1972 [40]. The reaction carried out in severe con-
ditions was characterized by low selectivity and low to
medium yields.
R2O
O
A
The practical application of organophosphorus
compounds includes their use in the membranes of fuel
elements [22], in optical materials [23–25], as flame
retardants (antipyrenes) [26–29], and as ligands in
catalytic reactions [30–33]. The growing demand for the
preparation of new ligands for highly efficient catalytic
systems is among the driving forces in the field of the
organophosphorus chemistry.
Tanaka et al. for the first time carried out the hydro-
phosphorylation catalyzed with palladium complexes in
1996 [41]. The addition of (MeO)2P(O)H to alkynes in
the presence of palladium catalyst under mild conditions
(67°C, 15–20 h) afforded vinylphosphonates in high
yields (Scheme 1).
We had formerly developed a catalytic system Pd2d-
ba3–PPh3–CF3COOH [42] that was successfully tested on
The intensive development of the transition metal
1099

IVANOVA et al.
1100
a hydrophosphorylation of a series of alkynes (Scheme 2).
The high regio- and stereoselectivity allowed the prepa-
ration of addition products with excellent yields and purity.
The study of the reaction mechanism showed that the addi-
tion of CF3COOH to the catalytic system was a necessary
condition of the suppression for the side reactions.
In the course of further research we found that the use
of Ni(acac)2 as the catalyst precursor made it possible to
carry out the reaction in the absence of the acid without
a decrease in the yield and the selectivity of the process.
We succeeded to apply the developed catalytic system
to carry out the addition of H-phosphonates both to ter-
minal and internal alkynes with an excellent regio- and
stereoselectivity [43, 44].
{(MeO)2P(O)H [41, 46], (Me2CO)2P(O)H [45, 46], and
(EtO)2P(O)H [46]} was known furnishing branched and
linear adducts, and also cyclic derivatives of vinylphos-
phonates.
The scanty published data on the diynes hydrophos-
phorylation, the latter being very interesting not only
for the synthesis of divinyldiphosphonates but for the
preparation of multiphosphorylated products, as well
prompted us to investigate these reactions. Here we pres-
ent the catalytic system Ni(acac)2–(i-Bu)2AlH that we
have developed for the hydrophosphorylation of diynes.
The developed synthetic procedure excludes the applica-
tion of organic solvents and toxic phosphine ligands in
keeping with the requirements of the “green chemistry”.
Up till now catalytic hydrophosphorylation of vari-
ous classes of unsaturated compounds (alkenes, dienes,
alkynes) has been studied [34]. However only scanty
examples exist for the catalytic hydrophosphorylation of
diynes (Scheme 3) [41, 45, 46]. It should be mentioned as
well that only the addition of the simplest H-phosphonates
As a model reaction we chosen the addition of
diisopropyl-H-phosphonate (Ia) to 1,6-heptadiyne (IIa)
using Ni(acac)2 as catalyst precursor (Scheme 4). The
stable in air and cheap Ni(acac)2 has obvious advantages
over the expensive palladium complexes and unstable
compounds of Ni(0).
Scheme 1.
R
3 mol% [Pd]
3 мол% [Pd]
(MeO)2P(O)H
R
THF, 67°С,
P(O)(OMe)2
89_95%
15_20 h
[Pd] = cis-PdMe2(PPh2Me)2; R = Ar, Alk.
Scheme 2.
R1
R2
O
_
_
Pd2dba3 PPh3 CF3COOH
THF, 50_70°C, 4_8 h
(R3O)2P
R1
R2
+
H
(R3O)2P
O
11 examples
y lds 65–9
theirieyields 65
6_%96%
R1 = Alk; R2 = H, Et; R3 = Alk, Ar.
Scheme 3.
O
O
2(MeO)2P(O)H
(MeO)2P
Z
P(OMe)2
Z
3 mol% [Pd],
THF, 67°C, 15_20 h
(CH ) , 83%
,
Z = (CH22)55 83%
[Pd] = cis-PdMe2(PPh2Me)2
,
Z =
87%
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

SYNTHESIS OF ALKYL TETRAPHOSPHONATES
1101
The ratio being reagents Ia and IIa of 2 : 1 was
chosen initially aiming at selective synthesis of divinyl-
diphosphonate B as a result of the addition of two
molecules of H-phosphonate Ia to both triple bonds of
diyne IIa.
Table 1. Variation of promoters in the addition reaction of
diisopropyl-H-phosphonate (Ia) to 1,6-heptadiyne (IIa)
Yield, %a
Run
no.
Conversion
Ligand Additive
of Ia, %a
IIIa
0
IVa
0
1
–
–
0
0
O
O
2b DPPM
3b DPPE
4b DPPB
–
0
0
(i-PrO)2P
P(OPr-i)2
3
–
–
0
0
0
0
0
0
B
5c
–
(i-Bu)2AlH
100
79
19
In the absence of a phosphine ligand the formation of
product B was not observed, and the only signal registered
in the 31P{1H} NMR spectrum belonged to the initial
H-phosphonate Ia (Table 1, run no. 1). The introduction
of bidentate phosphine ligands (Table 1, runs nos. 2–4)
to the system also did not result in the formation of the
target divinyldiphosphonate B. In particular, the system
Ni(acac)2–DPPE (Table 1, run no. 3) which high effi-
ciency in the hydrophosphorylation of alkynes, including
1-heptyne, was demonstrated earlier [44], was inactive
in the case of diynes.
Calculated from 31P{1H}NMR spectrum;
b Conditions: 1 mmol of Ia, 0.5 mmol of IIa, 4 h, 100°C, 6 mol% of
Ni(acac)2, 12 mol% of ligand;
Conditions: 1 mmol of Ia, 0.5 mmol of IIa, 24 h, 120°C, 9 mol%
a
c
of Ni(acac)2, 18 mol% of (i-Bu)2AlH.
lacking. To establish the number of formed products
the reaction mixture in the first stage was subject to
31P DOSY NMR [47].
The analysis of the DOSYspectrum allowed the sepa-
ration of the main components present in the 31P NMR
spectrum by their self-diffusion coefficients. Two dou-
blets at 28.8 and 30.9 ppm proved to belong to the same
component, log(D) = –10.22 ± 0.07 IIIa, whereas the
singlet at 26.1 ppm corresponded to another molecule
with higher mobility [log(D) = –10.07 ± 0.05 IVa]. In the
DOSY spectrum the signals of the initial diisopropyl-H-
phosphonate (Ia), log(D) = –9.78 ± 0.16 (1JPH 687 Hz) and
It turned out that the application of diisobutylalumi-
num hydride led to the 100% conversion of H-phospho-
nate Ia within 24 h at 120°C (Table 1, run no. 5). In the
31P{1H} NMR spectrum of the reaction mixture after the
completion of the reaction two main signals accompanied
by the signals of side products of unknown nature were
observed. However in the 1H NMR spectrum of the re-
action mixture the characteristic divinyldiphosphonate
signals of vinyl protons in the region 4–6 ppm were
log D
–10.4
Product IIIa
Product IVa
–10.2
i PrO
i PrO
O
–10.0
–9.8
–9.6
P
OiPr
1JP–H = 687 Hz
i PrO
i PrO
O
P
5
H
40
35
30
25
20
15
10
0
–5 ppm
Fig. 1. 31P NMR DOSY spectrum of the reaction mixture.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

IVANOVA et al.
1102
Scheme 4.
_
( )
Ni(acac)2 (i-Bu)2AlH
120°С, 24 h
( )
+
3
[P]
[P]
[P]-H +
3
[P] [P]
[P]
[P]
IIIa
IVa
Ia
IIa
O
O
O
[P]-H =
P
H
of a side product of the reaction, triisopropyl phosphate,
log(D) = –9.86 ± 0.07, were also identified (Fig. 1).
characteristic pattern of the signals in the 31P{1H}NMR
spectrum allowed an assumption that adduct IIIa formed
via the addition of four molecules of diisopropyl-H-
phosphonate to the molecule of 1,6-heptadiyne (Fig. 3).
Regretfully, we failed to separate completely the
mixture obtained by the dry column chromatography.
The purest fraction contained a mixture of compounds
IIIa and IVa in 1 : 1 ratio. The establishment of the
structure of individual compounds was performed us-
ing 1H–31P HMBC, 1H–13C HSQC, and 1H–13C HMBC
NMR method. It turned out that compound IVa was a
product of the intramolecular cyclization of diyne with
two phosphorus-containing substituents (Fig. 2).
The observed spin-spin coupling constant JP–P in the
spectrum of compound IIIa equals 73 Hz. It corresponds
to typical values of 3JP–P for phosphate residues in similar
fragments [48, 49]. Yet the values 2JP–P and 4JP–P usually
do not exceed 10 Hz [50], therefore it is possible to as-
sign to compound IIIa the structure presented in Fig. 3.
This assumption is in agreement with the data of diffu-
sion NMR presented in Fig. 1: The tetraphosphorylation
product owing to the large mass and steric load is less
mobile in solution which corresponds to the observed
smaller self-diffusion coefficient.
Analogous cyclization product of heptadiyne with a
pinacol-H-phosphonate was described earlier [46]. In this
study we have performed a complete assignment of the
signals in the 1H and 13C{1H} NMR spectra of compound
IVa. The data of the chemical shifts and the multiplicity
of signals are listed in Table 2. The strong overlapping
of signals in the 1H and 13C{1H} NMR spectra impeded
their complete assignment for compound IIIa, but the
To get an independent confirmation of the assumed
structures of compounds IIIa and IVa the reaction mix-
ture was subjected to HPLC-MS analysis. The mixture
contained two prevailing substances IIIa and IVa with
retention time 1.2 and 1 min respectively, and also sev-
eral side products (Fig. 4). Found m/z 757.3743 (IIIa).
C31H68O12P4. Calculated [M + H]+ 757.3734, ∆ 1.2 ppm.
Found m/z 425.2222 (IVa). C19H38O6P2. Calculated [M +
H]+ 425.2216, ∆ 1.4 ppm.
O
O
P
P
O
O
O
O
The method HPLC-MS in contrast to HPLC-UV makes
Table 2. Chemical shifts in the 1H and 13C{1H} NMR spectra
of compound IVa (for numeration of atoms, see Fig. 2)
Fig. 2. Structure of compound IVa according to the NMR
spectroscopy. The arrows indicate the key 1H–13C and 1H–31P
HMBC correlations.
Atom no.
δ(1H)
1.28
δ(13C{1H})
3JP–P = 73 Hz
1
2
3
4
5
24.18
70.28
4.67
O
O
O
O
P
P
O
2.67 d (2JPH
18 Hz)
–
28.42 dd (1JPC 143, 4JPC 6 Hz)
P
O
P
O
O
O
O
O
O
130.11
37.39
2.49
1.82
6
21.92
Fig. 3. Assumed structure of multiphosphorylation product IIIa.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

SYNTHESIS OF ALKYL TETRAPHOSPHONATES
1103
x × 106
IIIa
IVa
IVa
3
IIIa
2
1
1
2
3
4
5 Time, min
Fig. 4. HPLC-MS chromatogram of the reaction mixture of model reaction.
zation of the conditions of the model reaction aiming at
increasing the yield of compound IIIa. Decreasing the
temperature from 120 to 100°C resulted in the reduc-
tion of compound IIIa yield from 79 to 51%, the yield
of compound IVa decreased insignificantly (from 19 to
15%), yet about 20% of H-phosphonate Ia did not react.
The use of 1 mol% of Ni(acac)2 at 120°C caused a sharp
decrease in the yield of compound IIIa from 79 to 36%,
whie the yield of compound IVa remained on the same
level (17%).
it possible to independently detect all components
simultaneously due to the variation in the intensity of each
definite m/z value with time. This feature of the detection
provides a possibility to avoid the laborious grading of
eluent composition, parameters of the chromatographic
column, and the separation conditions and permits
obtaining complete information on the composition
of a multicomponent mixture in one run (in this case
the time of analysis not exceeds 5 min). According to
HPLC-MS data compounds IIIa and IVa were the main
components of the obtained mixture; therewith the system
contained quite a number of the other impurity products
with phosphorus atoms in their composition which were
registered as small peaks in the 31PNMR DOSYspectrum
(Fig. 1, 4).
In accordance with the stoichiometry of adduct IIIa
formation the most favorable ratio of the reagents H-
phosphonate–diyne would be 4 : 1. However the increased
excess of the H-phosphonate in the reaction to three- and
fourfold did not result in a considerable increase in the
yield of the tetraaddition product. Therefore for the sub-
sequent experiments we chose the ratio H-phosphonate–
diyne 2 : 1.
Hence the structure of compound IVa and the assumed
structure of compound IIIa were confirmed by the data of
diffusion, heteronuclear correlation NMR spectroscopy,
and HPLC-MS analysis.
We carried out under the optimized conditions the
hydrophosphorylation of various diynes IIb–IId with
diisopropyl-H-phosphonate (Ia) (Table 3, runs nos. 1–3),
and also the hydrophosphorylation of 1,6-heptadiyne
(IIa) with various H-phosphonates Ib, Ic (Table 3, runs
nos. 4, 5). The performed experiments confirmed the high
efficiency of the catalytic system Ni(acac)2–(i-Bu)2AlH
for the synthesis of the product of multiphosphorylation.
In all cases the complete conversion of H-phosphonate I
was attained, and the corresponding alkyl tetraphospho-
It is noteworthy that the examples of the formation
of alkyl tetraphosphonates in catalytic reactions of H-
phosphonates with diynes were not known up today. The
catalytic system developed by us based on Ni(acac)2–(i-
Bu)2AlH allowed a hydrophosphorylation of diyne with
H-phosphonate with a 100% conversion of the latter and
a prevailing formation of alkyl tetraphosphonate IIIa.
We carried out a series of experiments on the optimi-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

IVANOVA et al.
Table 3. Hydrophosphorylation of diynes II with H-phosphonates I
1104
Run no.
Diyne II
H-phosphonate I
Conversion of I,%a
Yield of III,%a
Yield of IV,%a
i-PrO
O
P
91
IIIb
9b
4
1
100
i-PrO
H
IIb
Ia
i-PrO
O
H
70
IIIc
P
P
2
3
100
100
30b
10b
5
i-PrO
IIc
Ia
i-PrO
O
H
90
IIId
6
i-PrO
IId
Ia
EtO
O
45
IIIe
4
97
30c
P
3
EtO
H
IIa
Ib
PhO
O
H
56
IIIf
5e
100
8d
P
3
PhO
IIa
Ic
a
Calculated from the data of 31P{1H}NMR spectra. Conditions: 2 mmol of I, 1 mmol of II, 24 h, 120°C, 9 mol% of Ni(acac)2, 18 mol% of
(i-Bu)2AlH.
b Overall yield of compound IV and the other side products.
с
Overall yield of phosphorus-containing products of unknown structure 25%.
d Overall yield of phosphorus-containing products of unknown structure 36%.
e12 mol% Ni(acac)2, 24 mol% (i-Bu)2AlH.
nates IIIa–IIId were obtained in high yields.
mine the structure of compounds III and IV by the direct
analysis of the reaction mixture without preliminary
separation. The analysis of the data of diffusion 31PNMR
spectroscopy provides in a short time the fundamental
information on the number and type of the components
in the studied mixture of compounds. The existence of
this information allows carrying out further purposeful
analysis of the interesting components of the mixture with
the help of HPLC-MS and the other analytic methods. It
should be noted that such approach is especially suitable
to the study of the processes of synthesis of phosphorus-
containing hydrocarbons where often a large number of
reaction products are formed.
The system Ni(acac)2–(i-Bu)2AlH that we have de-
veloped is the first example of a nickel-based catalyst for
the addition of H-phosphonates to diynes. The addition
occurs without solvent, does not require the presence of
a phosphorus-containing ligand and permits the synthesis
of alkyl tetraphosphonates in high yields. The utilization
of catalytic amounts of cheap and stable against the air
oxygen and moisture Ni(acac)2 makes the procedure of
the synthesis cheap and easily available. The developed
catalytic system made it possible to prepare a series of
The catalyst based on Ni(acac)2–(i-Bu)2AlH proved
to be equally efficient for multiphosphorylation of diynes
with diverse lengths of the carbon chains (Table 1, run
no. 5; Table 3, runs nos. 1–3). In the case of diyne IIb
the corresponding cyclic compound IV formed in trace
amounts and the overall yield of side products did not
exceed 9% (Table 3, run no. 1).
The developed catalytic system Ni(acac)2–(i-Bu)2AlH
turned out to be suitable for the reactions with H-phos-
phonates containing the other substituents Ib, Ic, although
the selectivity of the process and the yield of the corre-
sponding compounds III were considerably lower in this
case (Table 3, runs nos. 4, 5). Such high sensitivity to the
variations in the structure of the substituent is character-
istic of this type of processes. The obtained compounds
IIIa–IIIe, IVa were characterized by the NMR spectros-
copy and high resolution mass spectrometry.
The main attention in this research we directed to the
development of an efficient physicochemical approach
to the study of the catalytic hydrophosphorylation of
diynes. The applied combination of the methods of NMR
spectroscopy and HPLC-MS made it possible to deter-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

SYNTHESIS OF ALKYL TETRAPHOSPHONATES
1105
new multiphosphorylated alkanes, valuable organophos-
phorus compounds.
a chromatographic column ZORBAX SB-C18 (2.1 ×
50.0 mm); the size of the particles of the stationary phase
1.8 μm, mobile phase acetronitrile–0.1% water solution of
formic acid, 9:1, elution in the isocratic mode, flow rate
0.25 ml min−1, temperature 25°C, the volume of injected
sample 0.01 μl. The analyzed mixture was dissolved in
acetonitrile (Merck, HPLC grade).
The detailed study of the mechanism of the reaction
described here is the object of further research. In par-
ticular, the important problems are discovering the role
of the metal in the stages of hydrophosphorylation of the
triple and double bonds, and also the nature of catalysis
and of the strong effect of the substituents in the diyne
and the H-phosphonate on the yield and the selectivity
of the reaction.
Mass spectrometric detection was performed on an
instrument Bruker maXis equipped with ESI ion source.
The measurements were carried out by registering the
positive ions (the voltage on the capillary 4500 V). The
range of mass scanning m/z 50–3000 Da, external calibra-
tion (Electrospray Calibrant Solution, Fluka). The eluate
from the analytic column of the chromatograph was
directly introduced into the ion source of the mass spec-
trometer, flow rate 0.25 ml min−1, spraying gas nitrogen
(8 l min−1), interface temperature 200°C.
EXPERIMENTAL
1D NMR spectra were registered on a spectrometer
Bruker DRX500 at operating frequencies 500.1, 125.8,
1
202.5 MHz for nuclei H, 13C, and 31P respectively.
The solvents for NMR experiments were stored over
molecular sieves. Chemical shifts are reported in the scale
δ, ppm. As internal reference for 1H and 13C{1H} NMR
spectra tetramethylsilane (1H) and solvent signals (13C)
were used. Chemical shifts in 31P{1H} NMR spectra are
reported with respect to external reference 85% water
solution of H3PO4. The error in the evaluation of the
yield from the 1P{1H} NMR spectra did not exceed 2%
[51].All spectra were processed with Bruker Topspin 2.1
software package.
High resolution mass spectra were measured on an
instrument Bruker micrOTOF II equipped with ESI ion
source. The measurements were carried out by registering
the positive ions (the voltage on the capillary 4500 V).
The range of mass scanning m/z 50–3000 Da, external
calibration (Electrospray Calibrant Solution, Fluka). The
acetonitrile (Merck, HPLC grade) solutions of substances
were injected by a syringe, flow rate 3 μl min−1, spraying
gas nitrogen (4 l min−1), interface temperature 180oC.
2D spectra were registered with a Bruker Avance II
600 NMR spectrometer equipped with a 5 mm BBO
probehead with Z-gradient coil. Standard pulse pro-
grams were used for the registration of COSY, HSQC
and HMBC NMR spectra. 2D 31P DOSY spectra were
obtained with a BrukerAvance II 600 NMR spectrometer
operating at 242.9 MHz for 31P. A standard 5 mm BBO
probehead with Z-gradient coil was used. Gradient field
strength was calibrated with 1% H2O/D2O sample (known
diffusion coefficient 1.90 × 10–9 m2s−1 at 25°C) and ap-
peared to be 6.50 G cm−1 A−1. The spectra were acquired
with air flow switched off to prevent convection artifacts.
Standard pulse program stegp1s (stimulated echo with one
spoil gradient) was used. 31P DOSY NMR spectra were
registered without proton decoupling. The duration of
gradient pulse and diffusion time were set to 1500 μs and
400 ms, respectively. 128 diffusion points were acquired
with 32 scans per point and linear gradient increment
from 5 to 95%. 2D DOSY spectra were generated using
Bruker Topspin 2.1 software package.
All reagents were commercial products and were used
after spectral testing their purity (1H, 13C{1H}, 31P{1H}
NMR spectroscopy). Ni(acac)2 before use was dried in a
vacuum (3 Pa, 70°C, 2 h).
All reactions were carried out in PTFE screw capped
tubes, equipped with a magnetic stirrer bar. In all cases
reaction vessels were flushed with argon before heating.
Hydrophosphorylation in the system Ni(acac)2–
(i-Bu)2AlH. The mixture of diyne II (1 × 10–3 mol),
H-phosphonate I (2 × 10–3 mol), and Ni(acac)2 23.1 mg
(9 × 10–5 mol), was stirred for 5 min. To the formed ho-
mogeneous green solution at stirring and constant argon
flow was added 0.18 ml of 1 M solution of (i-Bu)2AlH
in THF; at the moment of the addition the color of the
solution changed from green to black. The reaction was
carried out at 120°C over 24 h.
The experiments with the use of phosphine ligands
(Table 1) were carried out along procedure [44].
The purification of the products was carried out by
vacuum chromatography on a dry column with a gradient
elution [52]; silica gel 0.015–0.040 mm (Merck); eluent
ethyl acetate–ethanol, 1.5 : 1 (IIIa, IVa); hexane–metha-
The separation by the method HPLC was carried
out on a chromatograph Agilent 1200 equipped with
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

IVANOVA et al.
1106
nol, 1.5 : 1 (IIIb–IIIe). The solvents were purified by
known procedures [53].
nos. 13-03-01210, 12-03-33127, 12-03-31518), and of
the Ministry of Education and Science of the Russian
Federation (grant no. 8453, 8572).
Octaisopropyl (heptane-1,2,6,7-tetrayl)tetrakis-
1
phosphonate (IIIa). Yellow oily substance. H NMR
spectrum (CDCl3), δ, ppm: 1.18–2.25 m (60H), 4.60–
4.78 m (8H). 31P{1H} NMR spectrum (CDCl3), δ, ppm:
28.8 d (3JP–P 73.0 Hz), 30.9 d (3JP–P 73.0 Hz). Mass spec-
trum: m/z 757.3744 [M + H]+. C31H68O12P4. Calculated:
757.3734, Δ 1.3 ppm
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Tetraisopropyl [cyclopent-1-ene-1,2-diyldi-
(methylene)]bisphosphonate (IVa). Yellow oily sub-
stance. 1H NMR spectrum (CDCl3), δ, ppm: 1.26–1.29 m
(24H), 1.78–1.86 m (2H), 2.46–2.52 m (4H), 2.67 d (4H,
J 18 Hz), 4.64–4.69 m (4H). 31P{1H} NMR spectrum
(CDCl3), δ, ppm: 26.1. Mass spectrum: m/z 425.2216
[M + H]+. C19H38O6P2. Calculated: 425.2216, Δ 0 ppm
Octaisopropyl (octane-1,2,7,8-tetrayl)tetrakisphos-
1
phonate (IIIb). Yellow oily substance. H NMR spec-
trum (CDCl3), δ, ppm: 1.16–2.27 m (62H), 4.61–4.76 m
(8H). 31P{1H} NMR spectrum (CDCl3), δ, ppm: 28.8 d
(3JP–P 76.5 Hz), 31.0 d (3JP–P 76.5 Hz). Mass spectrum:
m/z 793.3687 [M + Na]+. C32H70O12P4. Calculated:
793.3710, Δ 2.9 ppm
8. Harnden, M.R., Parkin,A., Parratt, M.J., and Perkins, R.M.,
J. Med. Chem., 1993, vol. 36, p. 1343.
Octaisopropyl (nonane-1,2,8,9-tetrayl)tetrakis-
phosphonate (IIIc). Yellow oily substance. H NMR
9. Lazrek, H.B., Rochdi, A., Khaider, H., Barascut, J.-L.,
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1
spectrum (CDCl3), δ, ppm: 1.22–2.25 m (64H), 4.58–
4.85 m (8H). 31P{1H} NMR spectrum (CDCl3), δ, ppm:
28.8 d (3JP–P 77.6 Hz), 31.1 d (3JP–P 77.6 Hz). Mass spec-
trum: m/z 807.3867 [M + Na]+. C33H72O12P4. Calculated:
807.3866, Δ 0.1 ppm
Octaisopropyl (decane-1,2,9,10-tetrayl)tetrakis-
1
phosphonate (IIId). Yellow oily substance. H NMR
spectrum (CDCl3), δ, ppm: 1.16–2.24 m (66H), 4.64–
4.74 m (8H). 31P{1H} NMR spectrum (CDCl3), δ, ppm:
28.8 d (3JP–P 78.1 Hz), 31.1 d (3JP–P 78.1 Hz). Mass spec-
trum: m/z 821.4012 [M + Na]+. C34H74O12P4. Calculated:
821.4023, Δ 1.3 ppm
Octaethyl (heptane-1,2,6,7-tetrayl)tetrakisphos-
1
phonate (IIIe). Yellow oily substance. H NMR spec-
trum (CDCl3), δ, ppm: 1.27–2.30 m (36H), 4.02–4.18 m
(16H). 31P{1H} NMR spectrum (CDCl3), δ, ppm: 30.6 d
(3JP–P 65.2 Hz), 32.8 d (3JP–P 65.2 Hz). Mass spectrum:
m/z 667.2312 [M + Na]+. C23H52O12P4. Calculated:
667.2301, Δ 1.7 ppm.
ACKNOWLEDGMENTS
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The study was carried out under the financial support
of the Russian Foundation for Basic Research (grants
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 8 2013

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