Isolation of a metastable geometrical isomer of a hexacoordinated dihydrophosphate: Elucidation of its enhanced reactivity in umpolung of a hydrogen atom of water

Article abstract of DOI:10.1021/ic2012765

Two of five conceivable geometrical isomers of a hexacoordinated dihydrophosphate bearing two sets of a bidentate ligand were investigated. X-ray crystallographic analysis of both of isomers, 1a-TPP and 1b-TEA, revealed their octahedral geometries of C₂ and C₁ symmetry, respectively, which were consistent with the NMR spectra. The isomer 1b-TEA underwent both hydride reduction of an aldehyde and proton exchange with water at room temperature in DMSO without any additive. A one-pot reaction of both of the reactions of 1b-TEA with D₂O and an aldehyde or a ketone under the above conditions proceeded successfully to give the deuterated alcohol. Thus, umpolung of a hydrogen atom of water with 1b-TEA was achieved under much milder conditions than those used in the reaction with another isomer, 1a-TEA. Quantitative isomerization of 1b-TEA to 1a-TEA occurred in methanol at room temperature. Calculations on the five conceivable geometrical isomers of the anionic part of the dihydrophosphate revealed their relative stability, which reasonably explained the isomerization, and the larger negative charge at the atoms located at the trans positions of the oxygen atoms. The smaller coupling constants of the P-H and P-C bonds located at the rear of an oxygen atom in the NMR spectra resulted in the smaller s character of these bonds. The differences in both hydride-donation and proton-exchange reactivities between 1a-TEA and 1b-TEA could be explained by the differences in the atomic charge of the hydrogen atom and the stability difference of the initially formed phosphorane intermediates, respectively.

Full text of DOI:10.1021/ic2012765

ARTICLE
pubs.acs.org/IC
Isolation of a Metastable Geometrical Isomer of a Hexacoordinated
Dihydrophosphate: Elucidation of Its Enhanced Reactivity in
Umpolung of a Hydrogen Atom of Water
Hideaki Miyake, Naokazu Kano,* and Takayuki Kawashima*,†
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
S Supporting Information
b
ABSTRACT: Two of five conceivable geometrical isomers of a
hexacoordinated dihydrophosphate bearing two sets of a bi-
dentate ligand were investigated. X-ray crystallographic analysis
of both of isomers, 1a-TPP and 1b-TEA, revealed their
octahedral geometries of C2 and C1 symmetry, respectively,
which were consistent with the NMR spectra. The isomer 1b-
TEA underwent both hydride reduction of an aldehyde and
proton exchange with water at room temperature in DMSO
without any additive. A one-pot reaction of both of the reactions
of 1b-TEA with D2O and an aldehyde or a ketone under the above conditions proceeded successfully to give the deuterated alcohol.
Thus, umpolung of a hydrogen atom of water with 1b-TEA was achieved under much milder conditions than those used in the
reaction with another isomer, 1a-TEA. Quantitative isomerization of 1b-TEA to 1a-TEA occurred in methanol at room
temperature. Calculations on the five conceivable geometrical isomers of the anionic part of the dihydrophosphate revealed their
relative stability, which reasonably explained the isomerization, and the larger negative charge at the atoms located at the trans
positions of the oxygen atoms. The smaller coupling constants of the PꢀH and PꢀC bonds located at the rear of an oxygen atom in
the NMR spectra resulted in the smaller s character of these bonds. The differences in both hydride-donation and proton-exchange
reactivities between 1a-TEA and 1b-TEA could be explained by the differences in the atomic charge of the hydrogen atom and the
stability difference of the initially formed phosphorane intermediates, respectively.
Chart 1. Dihydrophosphates 1a-TEA, 1a-TPP, and 1b-TEA
’ INTRODUCTION
Umpolung,1 the reversal of polarity of an atom in a functional
group, is one of the most useful concepts in organic synthesis.
Umpolung of a hydrogen atom is relatively difficult because a
proton source, such as water (Hδ+ꢀOH), undergoes a reaction
with the product of the umpolung (HδꢀꢀZ) to give molecular
hydrogen. If umpolung of a hydrogen atom of a water molecule
could be achieved, it would provide deuteride ion (Dꢀ) and
tritide ion (Tꢀ) donors from heavy water (D2O or T2O). This
method should be useful for isotope labeling,2 which is widely
used in the study of biomolecules and reaction mechanisms,
because heavy water is cheap and easy to use. Although a number
of studies have reported on the development of isotope-labeling
methods using D2O under strongly acidic conditions, at high
temperatures, or in the presence of transition metal catalysts, the
deuterium does not work as a deuteride ion in those cases.3
We recently reported the synthesis of novel hexacoordinated
phosphates 1a-TEA and 1a-TPP and their application to hydride
reduction of carbonyl compounds in a preliminary communica-
tion (Chart 1).4 Interestingly, a hydrogen atom on the phos-
phorus atom of 1a-TEA was not only reactive as a hydride but
also exchangeable for a proton of water, resulting in umpolung of
a hydrogen atom of water. However, the reactivity is low, so the
reactions needed heating or additives. Considering that geome-
trical isomerism of some pentacoordinated organophosphorus
compounds results in different stability, bonding properties, and
reactivities,5 another geometrical isomer of the hexacoordinated
phosphorus compounds is expected to show enhanced reactiv-
ities. Here, we report the synthesis and isolation of hexacoordi-
nated dihydrophosphate 1b-TEA, in which the phosphorus atom
forms bonds with two Martin ligands6 and two hydrogen atoms
in a spatial arrangement different from that of 1a-TEA. The
newly isolated isomer 1b-TEA has higher reactivity than 1a-TEA
for both the hydride reduction and the proton exchange, and
thus, umpolung of a deuterium atom in D2O was achieved at
room temperature without any additive.
Received: June 13, 2011
Published: August 23, 2011
r
2011 American Chemical Society
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Scheme 1. Synthesis of 1a-TEA and 1b-TEA
Table 1. Crystallographic Data for 1a-TPP and 1b-TEA
1a-TPP
1b-TEA
color
colorless
colorless
formula
C42H30F12O2P2
856.60
C26H30F12NO2P
647.48
fw
temp/K
120(2)
120(2)
cryst syst
space group
a/Å
monoclinic
P2/n
monoclinic
P21/c
13.8932(17)
7.3216(9)
18.572(3)
98.415(3)
1868.8(4)
2
18.436(4)
16.567(3)
20.034(5)
114.4158(7)
5572(2)
8
b/Å
c/Å
β/deg
V/Å3
Z
dcalcd/g cmꢀ3
unique reflns
R indices [I > 2σ(I)]
R indices (all data)
GOF
1.522
1.544
11 729
12 690
0.0377
0.0354
0.1047
0.0956
1.064
1.044
Chart 2. Five Possible Geometrical Isomers of the Dihydro-
phosphate Bearing Two Martin Ligandsa
aNumbers in parentheses are relative energies (kcal molꢀ1) calculated at
the MP2/6-31+G(d,p)//B3PW91/6-31+G(d,p) level.
1a-TPP show C2 symmetry for their anion moiety. Therefore,
both of the crystallographically symmetric bonds of the PꢀH,
PꢀO, and PꢀC bonds in 1a-TPP naturally show the same
length, whereas they do not in 1b-TEA. For example, both of the
PꢀH bond lengths of 1a-TPP are 1.354(18) Å, whereas the
PꢀH bond lengths of 1b-TEA are 1.382(16) and 1.318(14) Å.
The 1H, 13C, 19F, and 31P NMR spectra (DMSO-d6) of 1b-
TEA indicate that it has the same structure as that in the
crystalline state, as described below. In the 31P NMR spectrum,
1b-TEA showed a doublet of doublets at δP ꢀ177.7 ppm with
two nonequivalent coupling constants between the 31P and the
1H nuclei (1JPH = 661, 319 Hz) while 1a-TEA showed a triplet at
δP ꢀ169.1 ppm (1JPH = 343 Hz). Both signals in the very high
field region indicated the hexacoordinated state of both phos-
phorus atoms in solution. Observation of the aforementioned
nonequivalence in coupling constants of 1b-TEA as well as two
signals due to two nonequivalent protons (δ 6.85, 7.13 ppm) in
the 1H NMR spectrum supported a 1bꢀ structure among the five
possible geometrical isomers, 1aꢀꢀ1eꢀ, for the present hexa-
coordinated phosphate anion (Chart 2). The four other isomers
do not correspond to the observations because their two protons
binding to the phosphorus atom are equivalent in 1aꢀ and
1cꢀꢀ1eꢀ. In addition, the 1bꢀ structure of 1b-TEA was supported
by observation of four quartets of nonequivalent trifluoromethyl
groups in both the 13C and the 19F NMR spectra.
Figure 1. ORTEP drawings of (a) 1a-TPP and (b) 1b-TEA (50%
probability thermal ellipsoids).
’ RESULTS AND DISCUSSION
In our previous paper, we reported that we obtained hexa-
coordinated dihydrophosphate 1a-TEA from hydrophosphor-
ane 2 using THF as a solvent (Scheme 1).4 Here, we succeeded in
synthesizing dihydrophosphate 1b-TEA by changing solvents
from THF to diethyl ether and dimethyl sulfoxide (DMSO) in
the reduction and cation exchange, respectively. X-ray crystal-
lographic analysis of 1b-TEA revealed that it is a geometrical
isomer of 1a-TEA with a differently arranged bidentate ligand
(Figure 1, Table 1). Although two different geometrical isomers
have been successfully isolated in some pentacoordinated orga-
nophosphorus compounds,5 this is the first example for a
hexacoordinated phosphate as far as we know.7 The phosphate
anion moiety of 1b-TEA shows C1 symmetry, while 1a-TEA and
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Scheme 2. HꢀD Exchange Reaction of 1a-TEA and 1b-TEA
Scheme 4. One-Pot Reaction
Table 2. Calculated Atomic Charges (q) and PꢀH and PꢀC
Coupling Constants (J)
Scheme 3. Hydride Reduction of an Aldehyde Using 1a-TEA
or 1b-TEA as a Hydride Donor
JPC
(Hz) a
JPH
(Hz) a
a
a
qP
qO
qC
qH
1aꢀ 1.54 ꢀ0.90
ꢀ0.31
ꢀ0.13
115
260
1bꢀ 1.55 ꢀ0.89 (O1) ꢀ0.30 (C1) ꢀ0.07 (H1) 123 (PꢀC1) 576 (PꢀH1)
ꢀ0.90 (O2) ꢀ0.35 (C2) ꢀ0.14 (H2) 13 (PꢀC2) 231 (PꢀH2)
a The bold numbers are the values for the nuclei located at the position
trans to the oxygen atoms.
of the phosphate, and second, the PꢀH groups of the phosphate
have to show hydridic reactivity. Because the dihydrophosphate
1b-TEA was found to satisfy both of these requirements, it was
subjected to successive reactions without any separation process
to demonstrate its utility for the umpolung. A one-pot reaction of
the HꢀD exchange from 1b-TEA to 1b-TEA-d2 using D2O
followed by reduction of 4-PhC6H4CHO proceeded successfully
at room temperature in DMSO without any additive to give the
deuterated alcohol (76% yield, 94% D) and hydrophosphorane 2
(91%) (Scheme 4), while the one-pot reaction using 1a-TEA
needed addition of acetic acid.4 The one-pot reaction using a
ketone and 1b-TEA similarly proceeded without any additive,
although the yield and D content declined to some extent.
The difference in the reactivities of the PꢀH bond between
these geometrical isomers should be explained by the physical
properties of each isomer, such as atomic charges of the hydrogen
atoms. Atomic charges (q) and coupling constants (J) of the
phosphate anions 1aꢀ and 1bꢀ, which are the anionic parts of 1a-TEA
and 1b-TEA, respectively, were calculated at the MP2/6-31+
G(d,p)//B3PW91/6-31+G(d,p) level for atomic charge and
B3PW91/6-31+G(d,p) level for coupling constants (Table 2).9
The calculated atomic charges of the central phosphorus atoms
(qP) of 1aꢀ and 1bꢀ were almost the same. However, the nega-
tive charges of the hydrogen atoms of 1aꢀ (ꢀ0.13) and of the H2
atom of 1bꢀ (ꢀ0.14) were somewhat larger than that of the H1
atom of 1bꢀ (ꢀ0.07). The hydrogen atoms with relatively high
negative charges are located at the positions trans to the oxygen
atoms. Similarly, the coupling constants were also influenced by
the atoms located at the trans positions. The calculated PꢀH
Dihydrophosphate 1b-TEA, a geometrical isomer of 1a-TEA,
is expected to have different reactivities from those of 1a-TEA.
As we already reported, treatment of 1a-TEA with deuterium
oxide in the presence of acetic acid gave deuterated phosphate
1a-TEA-d2, showing its proton-exchange reactivity.4 Deutera-
tion did not occur at all without such an acid. In contrast, 1b-
TEA was deuterated by treatment with deuterium oxide alone
(Scheme 2). Hence, the geometrical isomerism was found to
affect the reactivity of the proton exchange because deuteration
of 1b-TEA occurred much more easily than that of 1a-TEA. This
is a remarkable reactivity, because organophosphorus compounds
with a PꢀH bond scarcely exchange the hydrogen as a proton with
neutral water because of their weak acidity and basicity,8 whereas
many alcohols and amines easily exchange their protons with water.
Another important reactivity of 1a-TEA was its hydride-
reducing capability. In the case of reduction of 4-phenylbenzal-
dehyde to the corresponding alcohol using 1a-TEA as a hydride
donor, the reaction was completed after refluxing for 10 h in
THF, while the reaction at room temperature for 1 h resulted in
almost no reaction (only 5% conversion) (Scheme 3). However,
a similar reaction using 1b-TEA as a hydride donor was com-
pleted under much milder conditions (1 h at room temperature),
and the alcohol product was obtained in a good yield (89%).
Therefore, 1b-TEA turned out to be more reactive in both proton
exchange and hydride donation than its geometrical isomer, 1a-TEA.
There are two requirements to achieve the umpolung of water
by using the dihydrophosphate. First, a hydrogen atom of water
has to be exchanged as a proton with hydrogens on the phosphorus
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coupling constants of 1aꢀ (260 Hz) and the PꢀH2 coupling
constant (trans to oxygen) of 1bꢀ (231 Hz) were also much
smaller than the PꢀH1 coupling constant (576 Hz) of 1bꢀ
(trans to carbon). These tendencies were also found in the
experimental values from the NMR measurements (1a-TEA,
Scheme 5. Plausible Mechanism of Isomerization from 1b-
TEA to 1a-TEA in a Protic Solvent
1
1JPH = 342 Hz; 1b-TEA, JPH = 319, 661 Hz), although the
calculated values were somewhat smaller than the experimental
values. These results clearly indicate the strong influence of
oxygen atoms on the atomic charges of the hydrogen atoms at the
trans positions and the coupling constants between the hydrogen
and the phosphorus nuclei. This is also true for atomic charges of
the carbon atoms and the PꢀC coupling constants, as shown in
Table 2.
The difference in the physical properties of each isomer
reflects the stability. The relative stabilities of all five conceivable
geometrical isomers of the dihydrophosphate bearing two Martin
ligands were calculated at the MP2/6-31+G(d,p)//B3PW91/6-
31+G(d,p) level. The most stable isomer, 1aꢀ, corresponds to
the anion moiety of 1a-TEA (Chart 2). Isomer 1aꢀ was
calculated to be 1.95 kcal/mol more stable than 1bꢀ. The newly
isolated isomer 1b-TEA corresponds to the second stable isomer.
Consideration of the solvation effect was expected to provide a
reason for the formation of 1b-TEA by changing the solvent in
the synthetic procedures. Single-point calculations on 1aꢀ and
1bꢀ using the integral equation formalismꢀpolarizable conti-
nuum model (IEFPCM) method10 were carried out to estimate
effects of the solvation of each isomer by THF and diethyl ether,
which were used for the syntheses, on the relative energies.
Isomer 1aꢀ was calculated to be 1.32 and 1.44 kcal/mol more
stable than 1bꢀ in THF and diethyl ether, respectively. There-
fore, selective isolation of the products cannot be explained by
solvation only, and any stronger interaction with the phosphates
must be taken into account to explain formation of 1b-TEA.
Judging from the experimental procedure for the synthesis of 1a-
TEA and 1b-TEA, phosphates 1aꢀ and 1bꢀ must exist as lithium
salts with some molecules of water used for workup before the
cation exchange. Therefore, we carried out calculations of
complexes 1a-LiꢀOH2 or 1b-LiꢀOH2, which are composed
of a lithium cation, one water molecule, and 1aꢀ or 1bꢀ, res-
pectively, at the MP2/6-31+G(d,p)//B3PW91/6-31+G(d,p)
level and found that 1b-LiꢀOH2 is 2.06 kcal/mol more stable
than 1a-LiꢀOH2.11 Thus, interaction with the lithium cation is
considered to invert the relative stability of 1aꢀ and 1bꢀ. When
the solvation was considered using the IEFPCM method, 1b-
LiꢀOH2 was more stable than 1a-LiꢀOH2 in both THF and
diethyl ether.11 Lithium salt 1b-LiꢀOH2 prefers to exist as a
contact ion pair in diethyl ether and, following cation exchange,
would give 1b-TEA. In THF, the phosphate would behave as a
free anion rather than the contact ion pair because THF strongly
solvates the lithium cation. Therefore, formation of the more
stable 1aꢀ would be favored in THF.
Scheme 6. Plausible Mechanism for the HꢀD Exchange
Reaction of 1a-TEA or 1b-TEA
to afford phosphine 4 (Scheme 5). Similarly, the isomer 1b-TEA
would afford 3b and 3b0 by protonation at the oxygen atoms
trans to the carbon and hydrogen atoms, respectively, and their
tautomerization also gives phosphine 4. Isomerization from 1b-
TEA to 1a-TEA in a protic solvent such as methanol would
proceed via pseudorotation and/or tautomerization among these
protonated intermediates.
Considering the calculated negative charge of the hydrogen
atoms of 1aꢀ and 1bꢀ, it is reasonable to suppose a reaction
mechanism involving interconversion of the PꢀH moiety to an
OꢀH moiety in the proton-exchange reactions of 1a-TEA and
1b-TEA. During the process from 1a-TEA or 1b-TEA to 4, one
of the hydrogen atoms on the phosphorus migrates to the oxygen
by protonation, being protic and exchangeable for water. There-
fore, the equilibration between 1a-TEA or 1b-TEA and 4 in the
presence of D2O allows deuteration of both dihydrophosphates
1a-TEA and 1b-TEA (Scheme 6). However, the HꢀD exchange
experiments showed a difference in the exchange reactivity
between 1a-TEA and 1b-TEA. To elucidate the reason for the
difference, the relative energies of 3a, 3b, 3b0, and 4 were studied
Quantitative isomerization of 1b-TEA to 1a-TEA occurred
within 10 min after dissolving it in methanol. The reverse reac-
tion was not observed. Therefore, 1b-TEA is less stable than 1a-
TEA in methanol, consistent with the above calculations on free
anions. In addition, the rate of isomerization was strongly
dependent on the solvent used: No detectable isomerization
occurred in either anhydrous THF or DMSO for 1 h. The active
proton of methanol would assist the isomerization (see below).
The experimental results indicate that active protons play
an important role in the isomerization. Protonation of 1a-TEA
gives dihydrophosphorane 3a, which undergoes tautomerization
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Figure 2. Optimized structures of 3a, 3b, 3b0, and 4 at the MP2/6-31+G(d,p)//B3PW91/6-31+G(d,p) level: orange, phosphorus; red, oxygen; gray,
carbon; green, fluorine; white, hydrogen.
Table 3. Calculated Relative Energies (kcal molꢀ1) of 3a, 3b,
3b0, and 4 at the MP2/6-31+G(d,p)//B3PW91/6-31+G(d,p)
Level Using the IEFPCM Method
Scheme 7. Plausible Reaction Mechanism of Hydride Do-
nation from 1aꢀ or 1bꢀ to an Electrophile (E+)
solvent
3a
3b
3b0
4
none
+3.41
+6.17
+4.50
0
+2.44
+2.62
+3.60
+1.50
DMSO
MeOH
+3.49
+2.75
0
0
by calculations at the MP2/6-31+G(d,p)//B3PW91/6-31+G(d,p)
level as free molecules and as solvated molecules using the
IEFPCM method considering solvation by DMSO and methanol
(Figure 2). Phosphorane 3b, the protonated form of 1bꢀ, was
calculated to be 3.41 kcal/mol more stable without solvation than
3a, the protonated form of 1aꢀ (Table 3). The calculated
structure of 3a indicated distortion from the idealized trigonal
bipyramidal structure, as indicated by the wide CꢀPꢀC angle
(143°). The calculated structure of 3b did not show such a
distortion, and 3b had a hydrogen bond between the OH group
and the other oxygen atom. Phosphorane 3b0, another proto-
nated form of 1bꢀ, was calculated to be 0.97 kcal/mol more
stable than 3a, because 3b0 adopted the more stable C-apical
conformation without distortion. Both 3b and 3b0 were calcu-
lated to be more stable than 3a in the cases of solvation by DMSO
and methanol, although the relative energies were different. In
addition, 1bꢀ was less stable than 1aꢀ, as described above. Com-
parison of the calculated relative energies of both the dihydro-
phosphates and the intermediate phosphoranes indicates that
protonation of 1bꢀ is easier than that of 1aꢀ. Therefore, it can be
reasonably understood that proton exchange of 1a-TEA required
assistance of a relatively strong acid, acetic acid, while the similar
reaction of 1b-TEA proceeded without assistance from such
an acid. In addition, the higher energy barrier of more than
6.17 kcal molꢀ1, the energy difference from 4 to 3a, would inhibit
isomerization of 1b-TEA to 1a-TEA in DMSO, and only the
HꢀD exchange reaction of 1b-TEA proceeded without isomer-
ization. In methanol, the difference in the energy barriers from 4
to 3a and to 3b or 3b0 is expected to be smaller. In addition,
protonation of 1bꢀ in methanol is easier than in DMSO with a small
amount of water, because the proton activity in methanol should be
higher than that in the latter system, judging from the comparison of
the pKa values of MeOH (15.50) and water in DMSO (31.4).12
Thus, isomerization from 1b-TEA to 1a-TEA in methanol occurred
easily, although isomerization was not observed in DMSO with a
small amount of D2O during the HꢀD exchange reaction.
explained by the higher hydride-donating ability of 1b-TEA
compared with 1a-TEA. The hydride-donating ability is sug-
gested by the negative atomic charge of one hydrogen atom of
1b-TEA (ꢀ0.14) being higher than that of 1a-TEA (ꢀ0.13)
(Table 2), although the difference is small. In addition, it is clearly
reflected by the s character of the PꢀH bond. Judging from the
fact that one of the PꢀH coupling constants JPH of 1b-TEA (1JPH
=
319 Hz) is smaller than that of 1a-TEA (1JPH = 342 Hz), the s
character of the corresponding PꢀH bond of 1b-TEA is smaller
than that of 1a-TEA. As a result, the hydridicity increases to produce
the higher hydride-donating ability of 1b-TEA.13 From the view-
point of the reverse relationship between the hydride-donating
ability and the PꢀH coupling constant, it is reasonable that other
previously reported hydrophosphates and dihydrophosphates with
larger PꢀH coupling constants than 1a-TEA and 1b-TEA, such as
ꢀ
F5PHꢀ (1JPH = 955 Hz),14a F4PH2ꢀ (1JPH = 936 Hz),14b Ph4PH2
(1JPH = 446 Hz),14c and CH3PF4Hꢀ (1JPH = 966 Hz),14d have not
been used as hydride donors.
Another factor affecting the hydride-donation reaction rate would
be the stability of intermediate products of the hydride donation.
The intermediate products of 1a-TEA and 1b-TEA would be
pentacoordinated phosphoranes 20 and 200, respectively, which
are unstable isomers of 2 (Scheme 7). They would give 2 under
the reaction conditions. Phosphorane 200 is considered to be more
stable than 20 because it has an oxygen atom at the apical position,15
and therefore, 1b-TEA would work as a more active hydride donor.
’ CONCLUSION
The differences in the reactivities of the hydride reduction of
1a-TEA and 1b-TEA are interpreted as follows. In the hydride
reduction, the higher reactivity of 1b-TEA than 1a-TEA can be
In summary, we synthesized and isolated a metastable geo-
metrical isomer of a hexacoordinated dihydrophosphate and
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investigated its properties and reactivities. The newly synthesized
dihydrophosphate 1b-TEA showed higher reactivity for both
proton exchange and hydride reduction, which are essential to
achieve umpolung of a hydrogen atom of water, than 1a-TEA.
The two reactivities, proton exchange and hydride reduction, are
usually thought to be opposite reactivities based on the opposite
polarity of a hydrogen atom, and therefore, it is intriguing that
both reactivities can be controlled by geometrical isomerism in
this case. Demonstration of reactivity differences by taking advan-
tage of the geometrical isomerism of hexacoordinated phos-
phorus species is important for phosphorus chemistry, in which
the geometrical isomerism of pentacoordinated phosphorus
species in particular has been studied. The higher reactivities of
1b-TEA are explained by the larger negative charge of the
hydrogen atom and higher stability of the reaction intermediate,
with both changes caused by differences in the spatial arrange-
ment of the ligands of 1a-TEA and 1b-TEA. The enhanced
reactivities of 1b-TEA enabled one-pot deuteration of an alde-
hyde and a ketone with D2O at room temperature without any
additive. This reductive deuteration of carbonyl compounds
under mild conditions will be useful for isotope labeling of some
compounds that are intolerant to acidic or basic conditions and
thermal conditions.
7.13 (dd, 1JPH = 661.4 Hz, 2JHH = 20.8 Hz, 1H), 7.21ꢀ7.28 (m, 1H),
7.38ꢀ7.57 (m, 4H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 7.2 (s),
51.6 (t, 1JNC = 3 Hz), 75.9 (sept, 2JCF = 29 Hz), 81.4 (sept, 2JCF = 28 Hz),
123.6 (d, JPC = 15 Hz), 123.8 (q, 1JCF = 287 Hz), 124.0 (q, 1JCF = 288
Hz), 124.2 (q, 1JCF = 289 Hz), 124.5 (q, 1JCF = 291 Hz), 124.8 (d, JPC = 8
Hz), 125.3 (d, JPC = 17 Hz), 125.9 (d, JPC = 2 Hz), 127.1ꢀ127.5 (m),
128.0 (d, JPC = 16 Hz), 128.3ꢀ128.5 (m), 132.5 (d, JPC = 16 Hz), 150.1
(d, JPC = 53 Hz), 152.6 (d, JPC = 167 Hz). 19F NMR (376 MHz, DMSO-
d6) δ ꢀ76.22 to ꢀ76.07 (br, 3F), ꢀ76.85 (q, 4JFF = 9.2 Hz, 3F), ꢀ75.54
(q, 4JFF = 9.5 Hz, 3F), ꢀ75.00 (q, 4JFF = 9.2 Hz, 3F). 31P NMR (162
1
MHz, DMSO-d6) δ ꢀ177.7 (dd, JPH = 661.4, 318.7 Hz); IR
(KBr, cmꢀ1) 2078, 2205 (PꢀH). Anal. Calcd for C26H30F12NO2P: C,
48.23; H, 4.67; N, 2.16. Found: C, 47.97; H, 4.77; N, 1.98.
HꢀD Exchange Experiments of Dihydrophosphate 1b-
TEA with D2O. Deuterium oxide (0.02 mL, 1.1 mmol) was added to a
DMSO-d6 solution (0.5 mL) of 1b-TEA (6.5 mg, 0.010 mmol). After
standing the reaction mixture for 30 min at room temperature, its 1H,
19F, and 31P NMR spectra showed signals due to dihydro-d2-phosphate
1b-TEA-d2 (96%, 97%D, estimated by 1H spectroscopy).
Reduction of Carbonyl Compounds with Dihydrophos-
phate 1b-TEA. A mixture of 1b-TEA (130 mg, 0.20 mmol) and
4-phenylbenzaldehyde (37 mg, 0.20 mmol) was dissolved in THF
(5 mL) and stirred for 1 h. 19F NMR monitoring showed that
consumption of 1b-TEA was more than 90%. After addition of an
aqueous solution of ammonium chloride, extraction with diethyl ether
and evaporation gave a crude solid. The solid was separated by silica-gel
chromatography to give 2 (94 mg, 91%) and 4-phenylbenzyl alcohol (33
mg, 89%). The products were identified by comparison of the data of 1H
NMR, GC-MS, and TLC with those of authentic samples.
Attempted Reduction of 4-Phenylbenzaldehyde with Di-
hydrophosphate 1a-TEA. A mixture of 1a-TEA (130 mg, 0.20 mmol)
and 4-phenylbenzaldehyde (37 mg, 0.20 mmol) was dissolved in THF
(5 mL) and stirred for 1 h. 19F NMR monitoring showed that consumption
of 1a-TEA was 5%.
One-Pot Reaction of the HꢀD Exchange of Dihydrophos-
phate 1b-TEA and Reduction of Cabonyl Compounds.
4-Phenylbenzaldehyde. Deuterium oxide (0.4 mL, 22 mmol) was added
to a DMSO solution (5 mL) of 1b-TEA (130 mg, 0.20 mmol) at room
temperature. After stirring for 30 min, a DMSO solution (2 mL) of
4-phenylbenzaldehyde (37 mg, 0.20 mmol) was added to it, and the
reaction mixture was stirred for 2 h at room temperature. After addition
of an aqueous solution of ammonium chloride, extraction with hexane
and evaporation gave a crude solid. The solid was separated by silica-gel
chromatography to give 2 (94 mg, 91%) and R-d-4-biphenylmethanol
(28 mg, 76%, 94%D).
’ EXPERIMENTAL SECTION
General Procedure. Solvents were dried and purified before use by
an MBRAUN MB-SPS solvent purification system. All reactions were
carried out under argon atmosphere. All NMR spectra were measured
with a JEOL AL400 spectrometer. Tetramethylsilane was used as an
external standard for 1H (400 MHz) and 13C NMR (100 MHz) spectra.
CF3CO2H (δ ꢀ77.7 ppm) and 85% H3PO4 were used as external
standards for 19F (376 MHz) and 31P NMR (202 MHz) spectra,
respectively. FAB-mass spectral data were obtained on a JEOL JMS-
700P. Infrared (IR) spectra were recorded on a JASCO FT/IR-420.
Melting points were recorded with a Yanaco micromelting point apparatus
and uncorrected. Elemental analyses were performed by the Micro-
analytical Laboratory of Department of Chemistry, Faculty of Science,
The University of Tokyo.
Caution: Contact with skin and eyes of hexafluorocumyl alcohol, a reagent
used for the synthesis of hydrophosphorane 2, and inhalation of its vapor or
mist should be avoided. Dihydrophosphates 1a-TPP and 1b-TEA should be
handled carefully because such organophosphorus compounds are potentially
toxic.
4-Acetylbiphenyl. After HꢀD exchange using deuterium oxide (0.4 mL,
22 mmol) and 1b-TEA (130 mg, 0.22 mmol) in DMSO (5 mL), a DMSO
solution (2 mL) of 4-acetylbiphenyl (39 mg, 0.20 mmol) was added to the
solution and the reaction mixture was stirred for 50 h at room temperature.
The above workup and chromatography gave R-d-1-biphenylethanol
(25 mg, 63%, 84%D) together with 2 (53 mg, 51%).
X-ray Crystallographic Analysis. Colorless single crystals of 1a-
TPP and 1b-TEA were obtained by recrystallization from CH2Cl2 and
used for X-ray diffraction data collection on a Rigaku Mercury charge-
coupled device diffractometer with a graphite-monochromated Mo KR
radiation. Data were collected and processed using CrystalClear (Rigaku).
Data were corrected for Lorentz and polarization effects. The structures
were solved by direct methods (SHELXS-97) and expanded using
Fourier techniques.16 The non-hydrogen atoms were refined anisotro-
pically. The hydrogen atoms at the benzene rings of 1a-TPP and
1b-TEA and ethyl groups of 1b-TEA were assigned by calculation and
refined isotropically by using a riding model. The hydrogen atoms at the
phosphorus atom of 1a-TPP and 1b-TEA were assigned by Fourier
method and freely refined isotropically. Crystal data are summarized in
Dihydrophosphate 1b-TEA. A diethyl ether solution (20 mL) of
phosphorane 2 (1.03 g, 2.0 mmol) was added to lithium aluminum
hydride (0.15 g, 4.0 mmol) at room temperature. After stirring for 1 h,
the reaction mixture was cooled to 0 °C and slowly quenched with water
(1 mL). After stirring for 30 min, the reaction mixture was filtered and
the residue was washed with diethyl ether (3 ꢁ 10 mL). The combined
filtrate and washings were evaporated to give a colorless solid. The solid
was redissolved in diethyl ether and evaporated again, and the process
was repeated two times. The resulting solid was dissolved in dimethyl
sulfoxide (20 mL), and a dimethyl sulfoxide solution (20 mL) of
tetraethylammonium bromide (0.63 g, 3.0 mmol) was added to the
solution. Water (10 mL) was slowly added to the reaction mixture with
cooling by a water bath to generate a colorless solid. The resulting solid
was filtered and washed with water and chloroform. Recrystallization of
the solid from acetone/ether gave dihydrophosphate 1b-TEA (0.56 g,
43%). Colorless crystals, mp 107ꢀ109 °C (decomp). 1H NMR
3
3
(400 MHz, DMSO-d6) δ 1.15 (tt, JHH = 7.3 Hz, JNH = 1.7 Hz,
12H), 3.19 (q, 3JHH = 7.3 Hz, 8H), 6.00ꢀ6.09 (m, 1H), 6.85 (dd, 1JPH
=
318.7 Hz, 2JHH = 20.8 Hz, 1H), 6.88ꢀ6.95 (m, 1H), 7.03ꢀ7.09 (m, 1H),
9088
dx.doi.org/10.1021/ic2012765 |Inorg. Chem. 2011, 50, 9083–9089

Inorganic Chemistry
ARTICLE
Table 1. More crystal data are available at the Cambridge Crystal-
lographic Data Centre, deposition nos. CCDC 729102 (1a-TPP) and
CCDC 814230 (1b-TEA).
Soc. 2002, 124, 13154–13170. (c) Kojima, S.; Kajiyama, K.; Nakamoto,
M.; Matsukawa, S.; Akiba, K.-y. Eur. J. Org. Chem. 2006, 218–234.
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Theoretical Calculation. Geometries of phosphate anions
1aꢀꢀ1eꢀ, lithium phosphate 1a-LiꢀOH2 and 1b-LiꢀOH2, dihydro-
phosphoranes 3a, 3b, and 3b0, and phosphine 4 were fully optimized
with density functional theory at the B3PW91/6-31+G(d,p) level, and
single-point calculation was performed at the MP2/6-31+G(d,p) level
using the GAUSSIAN 03 suite of programs.9 The solvent was taken into
account using the IEFPCM method.10 The Cartesian coordinates in
their optimized geometries are shown in Tables S1ꢀS11 in the
Supporting Information. Calculated atomic charges and PꢀH and
PꢀC coupling constants are shown in Table S12, Supporting Informa-
tion. Calculated relative energies using the IEFPCM method are shown
in Tables S13 and S14, Supporting Information.
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S., Daniels, A. D., Strain, M. C., Farkas, O., Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.;
Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham,
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03, revision C.01; Gaussian, Inc.: Wallingford, CT, 2004.
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J. Mol. Struct. (THEOCHEM) 1999, 464, 211–226.
(11) See Supporting Information.
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1980, 45, 3295–3299.
(13) Gudat, D.; Haghverdi, A.; Nieger, M. Angew. Chem., Int. Ed.
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’ ASSOCIATED CONTENT
S
Supporting Information. X-ray crystallographic data of
b
1a-TPP and 1b-TEA in cif format; spectral data of 1b-TEA and
theoretical calculation data for phosphate anions 1aꢀꢀ1eꢀ,
lithium phosphate 1a-LiꢀOH2 and 1b-LiꢀOH2, dihydrophos-
phoranes 3a, 3b, and 3b0, and phosphine 4. This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: kano@chem.s.u-tokyo.ac.jp (N.K.); Takayuki.Kawashima@
gakushuin.ac.jp (T.K.).
Present Addresses
†Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku,
Tokyo 171-8588, Japan.
’ ACKNOWLEDGMENT
This work was supported by research grants from the Global
COE program, the Sumitomo Foundation, General Sekiyu
Research & Development Encouragement & Assistance Founda-
tion, Grant-in-Aid for challenging Exploratory Research (23655030),
and for JSPS Fellows (19 6461) from the Japan Society for the
3
Promotion of Science. We thank Tosoh Finechem Corp. and Central
Glass Co., Ltd. for gifts of alkyllithiums and fluorine compounds,
respectively.
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