Phosphinite-phosphine oxide isomerization of diphenylphosphinite derivatives of 1,4:3,6-dianhydro-D-mannitol

Article abstract of DOI:10.1007/s11176-005-0171-8

Phosphorylation of 1,4:3,6-dianhydro-D-mannitol with diphenylphosphinous chloride provided a bisphosphinite derivative that, unlike what is observed in the phosphorylation with phosphorous chlorides and amides, undergoes fast phosphinite-phosphine oxide isomerization. The monophosphinite derivative, in addition, is strongly dephosphorylated. The effect of the solvents and amines (HCl acceptors) on the phosphinite-phosphine oxide isomerization is studied.

Full text of DOI:10.1007/s11176-005-0171-8

Russian Journal of General Chemistry, Vol. 75, No. 1, 2005, pp. 49 52. Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 1, 2005, pp. 56 60.
Original Russian Text Copyright 2005 by Kurochkina, Soboleva, Vasyanina, Grachev, Nifant’ev.
Phosphinite Phosphine Oxide Isomerization
of Diphenylphosphinite Derivatives
of 1,4:3,6-Dianhydro-D-mannitol
G. I. Kurochkina, N. O. Soboleva, L. K. Vasyanina, M. K. Grachev, and E. E. Nifant’ev
Moscow State Pedagogical University, Moscow, Russia
Received January 29, 2003
Abstract Phosphorylation of 1,4:3,6-dianhydro-D-mannitol with diphenylphosphinous chloride provided a
bisphosphinite derivative that, unlike what is observed in the phosphorylation with phosphorous chlorides and
amides, undergoes fast phosphinite phosphine oxide isomerization. The monophosphinite derivative, in
addition, is strongly dephosphorylated. The effect of the solvents and amines (HCl acceptors) on the phos-
phinite phosphine oxide isomerization is studied.
Recently the available and convenient-in-operation
1,4:3,6-dianhydro-Dmannitol (I), a compound that
possesses an internal chiral cavity, have been em-
ployed as an important starting material in fine or-
ganic synthesis, specifically, in the synthesis of
podands, crown ethers, phosphorus-containing car-
casses, bidentate bisphosphite ligands for metal
complex catalysts [2, 3], and complex macrohetero-
cyclic cavities of the basket-with-grip type [5].
1,4:3,6-Dianhydro-D-mannitol derivatives have also
been used as chiral building blocks [5]. Note that the
presence in condensed system I of two spatially
proximate hydroxy groups oriented endo with respect
to the internal cavity has predetermined some peculiar
features of the chemical behavior of this molecule,
for example, its tendency for di- rather than mono-
phosphorylation in reaction with equimolar amounts
of P(III) phosphorylating agent [3], as well as for
intramolecular phosphocyclization [3, 6].
Recently, aiming at preparing bidentate P(III)
ligands for metal complex catalysis, we phosphory-
lated diol I with chlorodiphenylphosphine (II) to
obtain bisphosphinite III that was isolaled pure and
immediately brought in oxidation or sulfurization to
form phosphinate ot thionophosphinate derivatives
[3]. The synthesis was carried out in a heterogenous
system including benzene, a poor solvent for diol I.
Note that bisphosphinite III is readily soluble in
benzene, and the reaction mixture got homogeneous
by the completion of the reaction.
Proceeding with our research in this field we dis-
covered that the synthesis of bisphosphinite derivative
III in homogeneous systems, for example, in DMF in
the presence of triethylamine or pyridine as HCl ac-
ceptors at 20 C, involves gradual convertion of bis-
phosphinite III ( 115 ppm) to a compound absorb-
P
ing at
33.2 ppm. This product was isolated pure in
P
86% yield by precipitation with hexane (see Experi-
mental) and identified as bis(phosphine oxide) IV.
H5
OH
H1a
O
H4
H3
H1b
H2
O
6 H6d
H
c
O
OH
I
PPh2
OPPh2
O
O
2.2B
I + 2Cl PPh2
2B HCl
II
O
O
PPh2
OPPh2
III
IV
O
1070-3632/05/7501-0049 2005 Pleiades Publishing, Inc.

50
KUROCHKINA et al.
1
The H NMR spectrum of compound IV contained
Effect of some compounds on the phosphinite III phos-
hine oxide IV isomerizationa
three groups of signals from protons of the dianhydro-
D-mannitol carcass: a multiplet at 3.89 4.04 ppm
(overlapping signals of the paired protons H1a, Hs6 and
H1b, H6d, with the integral intensity corresponding to
four protons), a doublet of doublets at 4.37 ppm and
the integral intensity corresponding to two protons,
and a multiplet at 4.75 4.85 ppm from the H2 and H5
protons (2H). The spectrum also contained two groups
of aromatic proton signals: multiplets at 7.43 7.55
(12H) and 7.79 7.97 ppm (8H).
Time, h
335
Catalyst
24
168
504 672
65/35 63/37 61/39 57/43 56/44
70/30 61/39 53/47 52/48 53/49
67/33 54/45 29/71 22/78 12/88
ZnCl2
C6H5OH
C3H7Br
[(CH3)2N+
CHBr]Br
74/26 14/86
8/92 4/96 4/96
23/77 16/84 14/86 5/95 5/95
Some specific features of the isomerization are
worth noting. The most important among them is that
the process in solution is accelerated by a suspension
of triethylamine hydrochloride. Therefore, we can
suggest that amine hydrochlorides catalyze this iso-
merization. Note that phosphine oxides can be easily
reduced to phosphines [7]. Hence, a combination of
phosphorylation and isomerization can be considered
a convenient synthetic approach to bisphosphines
which present special interest as bidentate ligands in
the synthesis of transition metal complexes. In view
of the practical importance of this isomerization, in
the present work we have studied the effect of sol-
vents on this process and undertook a search for other
effective catalysts for it. Comparative syntheses were
carried out under identical conditions at 20 C. The
reaction progress and the composition of the reaction
mixtures were followed by 31P NMR spectroscopy. It
was found in the synthesis of bisphosphine oxide IV
in DMF in the presence of 2.2 mol of triethylamine
the isomerization proceeds in 85% yield at 20 C
within 192 h. The yield in pyridine under the same
conditions is 80%. Similar results were also obtained
in separate experiments when pure bisphosphinite III
was kept in DMF with 2 mol of triethylamine hydro-
chloride.
BrCH2CH2CH2Br 33/67
6/94
0/100
[Ph(CH2N+Et2
C11H23)2]Br2
Br2 in CCl4
38/62 38/62 34/66 35/65 35/65
/50
/50
a
Molar ratio of phosphinite III to isomerized phosphine
oxide IV in the reaction mixture calculated from the ratio of
the integral intensities of their signals ( 115 and 30 ppm,
P
31
respectively) in the P NMR spectrum.
and subsequent phosphinite phosphine oxide iso-
merisation under the standard phosphorylation condi-
tions in DMF (below are given the residual contents
of phospinite III, mol%).
22 h
60
51 h
7
28
288 h
NEt3
6
7
32
(i-Pr)2NEt
PhNMe2
34
67
37
From the above data it follows that 22 h after the
reaction onset the isomerisation with diisoropylethyl-
amine has progressed much more profoundly (by
66%) compared to the other amines, but after 51 h the
31P NMR spectral pattern has changed, and the best
results proved to be observed with triethylamine.
After 288 h the intensity ratio of the P(III) and P(V)
product signals in the case of diisopropylethylamine
and thiethylamine was approximately equal. In the
case of dimethylaniline, the figures were significantly
higher than with the other two amines, which is
evidently explained by their higher basicity compared
to the aromatic amine.
Under the same conditions we have studied the
effect of some other compounds as potential catalysts.
They were added to the reaction mixtures in an
amount of 5 mol% of the amount of bisphosphinite
III (see table).
As seen from the table, the best results were ob-
tained with 1,3-dibromopropane: The isomerization
was complete in 14 days at room temperature. With
bromine in carbon tetrachloride, much by-products
formed along with target phosphine oxide IV. At the
same time, zinc chloride produced almost no catalytic
effect.
More intricate results were observed in the mono-
phosphorylation of diol I with phosphinous chloride
II at a 1:1 reagent molar ratio in DMF in the presence
of a 10% molar excess of triethylamine. By monito-
ring the reaction progress by 31P NMR we found that
monophoshorylated derivative V faster isomerizes into
monophosphine oxide VI than bisphosphinite III. For
example, the isomerization in DMF to form com-
We have also considered the effect of some amines
[NEt3, (i-Pr)2Net, PhNMe2] that are commonly used
as HCl acceptors in the synthesis of phosphinite III
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 1 2005

PHOSPHINITE PHOSPHINE OXIDE ISOMERIZATION
51
pound VI is complete in 120 h, while with bisphos-
phinite III under the same conditions the isomeriza-
tion degree is 22% in 144 h. Monophosphine oxide
VI was isolated pure in 74% yield. Contrary to what
mental conditions results in formation of a mono-
phosphorylated product, even though, according to
our previous findings [3], if the dianhydro-D-mannitol
residue contains an endo-hydroxy group, the phos-
phorylation with phosphorous acid amides and chlo-
rides yields diphosphorylation exclusively.
1
is observed with bisphosphinite III, the H NMR
spectrum of compound VI contains a double set of
related multiplet signals, that appears as a result of
disturbance of the molecular symmetry. The H6 signal
is a doublet of doublets at 3.5 ppm (1H). The Ha1
signal is a multiplet at 3.64 3.70 ppm (1H). The
overlapping H1b and Hd1 signals give a multiplet at
3.82 4.00 (2H). The H5 proton at the carbon atom
bearing the hydroxy group gives an upfield multiplet
signal at 4.14 4.27 ppm (1H), while the H2 proton
at the phosphorus atom gives a downfield signal at
4.70 4.86 ppm (1H). The H3 and H4 protons give two
Thus, our study showed that the phosphorylation
of 1,4:3,6-dianhydro-D-mannitol with diphenylphos-
phinous chloride takes a more intricate pathways than
with phosphorous chlorides and amides and is accom-
panied by phosphinite phosphine oxide isomerization.
The monophosphinite derivative, in addition, under-
goes profound dephosphorylation.
EXPERIMENTAL
neighboring doublets of doublets at
4.34 and
1
The H NMR spectra were registered on a Bruker
4.45 ppm (1H), respectively. Furthermore, the aro-
matic protons give two multiplets at 7.30 7.50 (6H)
and 7.64 7.90 ppm (4H).
WP-250 (250 MHz) spectrometer. The 31P {1H}
NMR spectra were obtained on a Bruker WP-80
1
(32.4 MHz) spectrometer. The H NMR spectra were
measured against internal TMS, and the 31P NMR
spectra, against external 85% phosphoric acid. All
syntheses were carried out under dry nitrogen in an-
hydrous solvents. Thin-layer chromatography was
carried out on Silufol UV-366 plates in 1:2 benzene
dioxane (A) and 1:1 benzene dioxane (B).
An important peculiarity of the monophosphoryla-
tion is gradual accumulation of diphenylphosphinic
acid (VII) ( P 21 ppm) in the reaction mixture at 20 C.
Simultaneously, intermediates (up to 5 mol%) are
detected in the reaction mixture (
20 to 25 ppm).
P
These signals appear at the beginning of dephospho-
rylation of compound VI and disappear when di-
phenylphosphinous acid VII is no longer accumulated.
The latter product was isolated pure from the reaction
mixture in 16% yield and identified (see Experimen-
tal). Based on published data [8], we can suggest that
the above-mentioned intermediates contain a five-
coordinate phosphorus. Note that the fast formation
of acid VII also occurs in the mono- and diphospho-
rylation performed in the absence of HCl acceptor,
2,5-Bis(diphenylphosphinoyl)-1,4:3,6-dianhydro-
D-mannitol (IV). To a mixture of 0.2 g of dianydro-D
mannitol I and 3 ml of DMF, 0.30 g of triethylamine
and 0.609 g of chlorodiphenylphosphine (II) were
added with stirring. The resulting mixture was left to
stand at 20 C under an inert gas. After 144 h its 31P
NMR spectrum showed signals at
33.2 ppm (integral intensity ratio 3:1). 1,3-Dibromo-
116.4 and
P
when HCl is removed with a slow flow of an inert gas. propane,1 0.005 g, was then added to the reaction mix-
ture, and it was left to stand at 20 C. After 336 h its
31P NMR spectrum showed a signal at
33.2 ppm.
OPPh2
The triethylamine hydrochloride was filtePred off, and
the solvent was removed in a vacuum. The residue
was dissolved in 2 ml of benzene, 1 ml of benzene
was added, and bisphosphine oxide IV was filtered off,
washed with hexane, and dried in a vacuum. Yield
0.6 g (86%), mp 138 139 C, Rf 0.6 (A), Rf 0.8 (B),
O
ClPPh2, 1.1B
I
O
OH
V
O
[ ]2D4 +53 (c 3.0, C6H6). H NMR spectrum (CDCl3),
1
, ppm: 3.89 4.04 m (4H, H1a, Hc6, Hb1, H6d), 4.37 d.d
PPh2
O
(2H, H3, H4), 4.75 4.85 m (2H, H2, H5), 7.43 7.55 m
(12H, CHarom). 31P NMR spectrum (DMF), P, ppm:
31.8. Found, %: C 69.99; H 5.58; P 12.01. C30H28
O4P2. Calculated,%: C 70.03; H 5.49; P 12.04.
O
+ HOPPh2
O
OH
VI
1
Noteworthy is the fact that the monophosphoryla-
tion with chlorodiphenylphosphine under our experi-
The other catalysts mentioned in the table were introduced
in a similar way.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 75 No. 1 2005

52
KUROCHKINA et al.
2-(Diphenylphoshinoyl)-1,4:3,6-dianhydro-D-
Serebryakov, E.P., Izv. Akad. Nauk SSSR, Ser. Khim.,
1988, no. 3, p. 632; El’perina, E.A., Serebryakov, E.P.,
and Struchkova M.I., Heterocycles, 1989, vol. 28,
no. 2, p. 805.
mannitol (VI). To a mixture of 0.305 g of dianhydro-
D-mannitol I in 8 ml of DMF, 0.23 g of triethylamine
and 0.46 g of diphenylchlorophosphine (II) were
added with stirring. The reaction mixture was left to
stand at 20 C. After 24 h its 31P NMR spectrum con-
2. Bredikhin, A.A., Bredikhina, Z.A., and Nigmatzya-
nov, F.F., Izv. Ross. Akad. Nauk, Ser. Khim., 1998,
no. 3, p. 426; Reetz, M.T. and Neugebauer, T.,
Angew. Chem. Int. Ed. Engl., 1999, vol. 38, nos. 1 2,
p. 179; Blackmond, D.G., Rosner, T., Neugebauer, T.,
and Reetz, M.T., Angew. Chem. Int. Ed. Engl., 1999,
vol. 38, no. 15, p. 2196; Reetz, M.T. and Mehler, G.,
Angew. Chem., Int. Ed. Engl., 2000, vol. 39, no. 21,
p. 3889.
tained two signals at
116.4 (V) and 33.4 ppm (VI)
P
(integral intensity ratio 5:1). The resulting mixture
was left to stand 20 C under an inert gas. After 120 h
its 31P NMR spectrum contained signals at
33.4
and 21.6 ppm (integral intensity ratio 5:1). TPhe tri-
ethylamine hydrochloride was filtered off. The filtrate
was left to stand at 0 C for 24 h. Diphenylphosphi-
nous acid (VII) precipitated and was filtered off. This
procedure was repeated until product VII no longer
precipitated. Yield 0.07 g (16%), mp 192 193 C
3. Gratchev, M.K., Anfilov, K.l., Bekker, A.R., and Ni-
fant’ev, E.E., Zh. Obshch. Khim., 1995, vol. 65,
p. 1946.
1
{published data: mp 193 194 C [9]}. H NMR spec-
trum (pyridine-d5), , ppm: 7.20 7.31 m (6H, CHarom),
4. Kurochkina, G.I., Grachev, M.K., Vasyanina, L.K.,
Piskaev, A.E., and Nifant’ev, E.E., Dokl. Ross. Akad.
Nauk, 2000, vol. 371, no. 2, p. 189; Grachev, M.K.,
Kurochkina, G.I., Soboleva, N.O., Vasyanina, L.K.,
and Nifant’ev, E.E., Zh. Obshch. Khim., 2002, vol. 72,
no. 11, p. 1918.
8.05 8.19 m (4H, CHarom), 11.95 s (1H, OH). 31P
NMR spectrum (DMF):
21.6 ppm.
P
The solvent was removed, and the oily residue was
washed with benzene (3 1 ml). Yield of compound
VI 0.51 g (74%), viscous light yellow oil, Rf 0.4 (A),
1
Rf 0.6 (B). H NMR spectrum (CDCl3), , ppm: 3.5
5. Bakos, J., Heil, B., and Marko, L., J. Organomet.
Chem., 1983, vol. 253, no. 2, p. 249; Cere, V., Maz-
zini, C., Paolucci, C., Pollicino, S., and Fava, A.,
J. Org. Chem., 1993, vol. 58, no. 17, p. 4567;
Loupy, A. and Monteus, D., Tetrahedron Lett., 1996,
vol. 37, no. 39, p. 7023; Chatti, S., Bortolussi, M.,
and Loupy, A., Tetrahedron Lett., 1996, vol. 37,
no. 39, p. 7023; Chatti, S., Bortolussi, M., and
Loupy, A., Tetrahedron Lett., 2000, vol. 41, p. 3367;
Jones, G.B. and Guzel, M., Tetrahedron Lett., 2000,
vol. 41, p. 4695.
d.d (1H, H6s); 3.64 3.70 m (1H, H1a), 3.82 4.00 m
(2H, H1b, H6d), 4.14 4.27 m (1H, H5), 4.34 d.d (1H,
H3), 4.45 d.d (1H, H4), 4.70 4.86 m (1H, H2), 7.30
7.50 m (6H, CHarom), 7.64 7.90 m (4H, CHarom). 31P
NMR spectrum (DMF):
30.8 ppm. Found, %: C
P
65.39; H 5.88; P 9.31. C18H19O4P. Calculated, %: C
65.45; H 5.80; P 9.38.
ACKNOWLEDGMENTS
The authors express their gratitude to the Russian
Foundation for Basic Research for financial support
of this work (project no. 02-03-32694).
6. Nifant’ev, E.E., Plotnikova, O.M., Ruchkina, N.G.,
Vasyanina, L.K., and Bekker, A.R., Zh. Obshch. Khim.,
1992, vol. 62, no. 11, p. 2456.
7. Wieser-Jeunesse, C., Matt, D., and DeCian, A.,
Angew. Chem. Int. Ed. Engl., 1998, vol. 37, no. 20,
p. 2861.
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