A General Protocol for the Synthesis of H-α-Hydroxyphosphinates

Article abstract of DOI:10.1055/s-0037-1610274

A general synthetic procedure was developed for H-α-hydroxyphosphinates via Abramov reaction. The present work is a complementary study to those reported till now. This methodology has the advantage that it can be applied to various aliphatic and (hetero)aromatic substrates. The H-α-hydroxyphosphinates were easily purified and obtained in good to excellent yields in shorter times. A ³¹ P NMR spectroscopy study has shown that only 2 equivalents of a silylating agent were required.

Full text of DOI:10.1055/s-0037-1610274

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–L
paper
A
en
J. Dussart et al.
Paper
Synthesis
A General Protocol for the Synthesis of H-α-Hydroxyphosphinates
Jade Dussart
O
P
O
P
1) silylating agent
R1
R2
Julia Deschamp*
Maelle Monteil
Olivier Gager
0
0
0
0
0-
0
0
2
1-
9
7
9
6-
9
1
3
H
OH
O
Na
H
R2
H
OH
2)
• short reaction time
• metal-free
• easy purification
R1
O
33 examples
Evelyne Migianu-Griffoni
Marc Lecouvey*
3) NaOH (aq)
36–100% yields
Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT,
CNRS UMR 7244, 93017 Bobigny Cedex, France
julia.deschamp@univ-paris13.fr
marc.lecouvey@univ-paris13.fr
Received: 03.08.2018
Accepted: 20.08.2018
Published online: 05.09.2018
DOI: 10.1055/s-0037-1610274; Art ID: ss-2018-e0527-op
synthetic pathways are reported in the literature to obtain
H-phosphinates from hypophosphite derivatives (direct
pathway) or from bis(trimethylsilyl)phosphonite (TMSO)2PH
(indirect pathway) (Scheme 1). The direct pathway involves
either a radical addition of hypophosphorous acid to
alkenes in the presence of a radical initiator (Et3B/O2;
AIBN)6 or a palladium-catalyzed cross-coupling reaction of
Abstract A general synthetic procedure was developed for H-α-hy-
droxyphosphinates via Abramov reaction. The present work is a com-
plementary study to those reported till now. This methodology has the
advantage that it can be applied to various aliphatic and (hetero)aro-
matic substrates. The H-α-hydroxyphosphinates were easily purified
and obtained in good to excellent yields in shorter times. A 31P NMR
spectroscopy study has shown that only 2 equivalents of a silylating
agent were required.
+
+
various hypophosphites MOP(O)H2 (M = H, PhNH3 , NH4 ,
Na+) and halide substrates RX [R = (hetero)aryl, alkenyl, al-
lylic, benzylic; X = I, Br, OTf, Cl, CH2Cl].7 The indirect path-
way usually involves the addition of excess in situ pre-
formed phosphonite (TMSO)2PH on various electrophiles8
such as alkyl halides,9 aldehydes/ketones,10 imines,11 and
α,β-unsaturated esters.12 For this indirect pathway, the
preparation of (TMSO)2PH is crucial and often inconvenient
as its preparation involves a large amount of silylating agent
(TMSCl/Et3N or BSA) or refluxing in the presence of HMDS
for several hours. Besides, the subsequent reactions be-
tween (TMSO)2PH and the various electrophiles often re-
quired extended reaction times. A large quantity of (TMSO)2PH
is often used in order to avoid the formation of symmetrical
disubstituted phosphinates.8,10g Although the two-step
strategy is well documented in the literature, no general
procedure can be efficiently used on various functionalized
substrates.
Keywords α-hydroxyphosphinate, synthetic methods, phosphorus,
phosphonylation, H-phosphinate
Phosphinates are an important class of organophospho-
rus compounds with a phosphorus atom attached to two
oxygens R1R2P(O)(OR) (R1/R2/R = hydrogen/carbon chain).
The P–C bond in phosphonates and even more in phosphi-
nates, provides a high stability and the ability to mimic
phosphate esters and carboxylates. Phosphinates represent
consequently interesting scaffolds for the development of
novel therapeutic molecules.1 More particularly, H-phosph-
inates (R1 = H, R2 = carbon chain) can be precursors of
phosphinates (R1/R2 = carbon chain) as phosphinic acid
pseudopeptides. These peptide isosteres contain a non-hy-
drolyzable phosphinic acid function instead of a peptide
bond that can mimic the substrate transition state for hy-
drolytic enzymes2 as matrix metalloproteinases (MMPs)3
and aspartic acid proteinases.4 Moreover, peptidomimetic
phosphinates are potent inhibitors in different pathologies
as cancer, neurodegenerative diseases, parasitic, and viral
diseases.5
O
direct
pathway
P
H
OM
O
P
O
P
H
+
M: H, PhNH3
NH4+, Na+
,
1
R2
R1
R1
H
OH
phosphinate
OH
H-phosphinate
indirect pathway
P
H
OSiMe3
OSiMe3
2
In this context, a straightforward and convenient access
to H-phosphinates still represents a major issue for the syn-
thesis of bioactive molecules. Several commonly general
Scheme 1 Synthetic pathways to phosphinates and H-phosphinates
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

B
J. Dussart et al.
Paper
Synthesis
For the past years our team has already studied and re-
ported the synthesis of substituted phosphinic acids.13
Herein, we disclose a complementary study in order to pro-
pose an easily handled general protocol for Abramov reac-
tion to synthesize α-hydroxyphosphinates. Our approach
does not necessitate the previous inconvenient preparation
of a hypophosphite salt and the use of excess amount of
(TMSO)2PH. Furthermore, our methodology furnishes easily
purified compounds in very satisfying yields and shorter
times than previously reported in the literature.8
(2 equiv)
SiMe3
Me3Si
N
3a
Ph
P
O
O
P
Me
H
O
SiMe3
O
OSiMe3
P
H
H
OH
O
H
H
HO
Me3Si
x 2
2
NH
1
2
Me
O
O
P
NaOH
(aq, 0.5 M)
Ph
OSiMe3
4a
H
5
OSiMe3
Scheme 2 Postulated mechanism of the Abramov reaction between
hypophosphorous acid (1) and benzaldehyde (3a) in the presence of
BSA as silylating agent
At the outset of this study, the equimolar Abramov reac-
tion was conducted with hypophosphorous acid (1) and
benzaldehyde (3a) in the presence of N,O-bis(trimethylsi-
lyl)acetamide (BSA) in dichloromethane at 0 °C (Table 1).
Initially, BSA (3 equiv) was dropwise mixed with hypophos-
phorous acid (1) over 40 minutes to generate in situ the
bis(trimethylsilyl)phosphonite (2), which was subsequently
added over 20 minutes to a solution of benzaldehyde (1
equiv) in dichloromethane at 0 °C (Table 1, entries 1–3:
method A). A 31P NMR spectrum after 1 hour indicated a to-
tal conversion and the expected α-hydroxyphosphinate 4a
was easily isolated as a solid sodium salt in a good yield of
70% (entry 1). We were also surprised that the reaction was
already complete at the end of the bis(trimethylsilyl)phos-
phonite (2) addition (entries 3 vs. 1 and 2). Moreover, sym-
metrically disubstituted phosphinate was not formed as
was generally observed in many other works.8,10h Indeed,
the excess of BSA could silylate the H-α-hydroxyphosphi-
nate to form a P(III) silylphosphonite. This P(III) specie may
compete with 2 for the addition onto 3a and thus form a
symmetrically disubstituted phosphinate as a side-product.
Thereafter, the previous procedure was modified in order to
easily handle the reaction, by directly adding the solution of
benzaldehyde (3a) onto the in situ bis(trimethylsilyl)phos-
phonite (2) (entry 4: method B). We were pleased to ob-
serve the formation of the expected α-hydroxyphosphinate
4a in a higher yield (85%). As previously mentioned, sym-
metrically disubstituted phosphinate was not detected.
Then, the reaction was carried out by decreasing the
amount of BSA (2 equiv) in the first step followed by the
method B procedure (entry 5). The reaction was successful
and the product 4a was obtained in an excellent yield (96%).
Although a large quantity of silylating agent is often used in
the literature to form the bis(trimethylsilyl)phosphonite (2)
starting from hypophosphorous acid (1), only 2 equivalents
are actually required to perform the silylation based on the
postulated reaction mechanism shown in Scheme 2.
acid. The hydrolysis of the silylated α-hydroxyphosphinate
5 finally leads to the resulting sodium α-hydroxyphosphi-
nate 4a.
Under the method B conditions, the reaction progress
was followed by 31P{1H} and 31P NMR in order to identify
the different P(III) and P(V) species proposed above (Figure
1). First of all, when the silylating agent BSA is added to hy-
pophosphorous acid (1), we observed the fast disappear-
ance of its signal (1, 12.8 ppm) and an emerging sole signal
in the P(III) region corresponding to the bis(trimethylsi-
lyl)phosphonite (2, 141.4 ppm). The coupling 31P NMR
spectra (in blue) show the fitting multiplicities a triplet for
Table 1 One-Pot Abramov Reaction of Benzaldehyde 3a and Hypo-
phosphorous Acid (1) in the Presence of N,O-Bis(trimethylsilyl)acet-
amide (BSA)a
O
BSA, CH2Cl2
P
P
H
OH
H
OSiMe3
OSiMe3
0 °C, 40 min
H
1
2
method A
2
O
P
Ph
O
3a
Ph
O
Na
3a
H
2
OH
method B
4a
Entry
BSA (equiv)
Methodb
Time (min)c
Yield (%)c,d
1
2
3
4
5
3
3
3
3
2
A
A
A
B
B
80
35
20
20
20
70
70
71
85
96
This reaction indeed could proceed because of the
P(V)/P(III) species equilibrium existing between hypopho-
phorous acid (1) and its phosphonite form. The silylation
actually allows the equilibrium displacement by trapping
the phosphonite. Then, the attack of 2 onto 3a may proceed
by a concerted five-membered-ring transition state in
which the TMS moiety may activate the aldehyde as a Lewis
a Reaction conditions: To a solution of 1 (10 mmol) in anhyd CH2Cl2 (2 mL)
was added dropwise BSA (20 mmol) under an argon atmosphere at 0 °C.
After 40 min, the adequate solution (method A or B) was added dropwise
to the reaction mixture under argon atmosphere at 0 °C, then the mixture
was quenched with aq 0.5 M NaOH.
b For details, see experimental section.
c The reaction was monitored by 31P NMR spectroscopy. The indicated time
includes the time of addition.
d Isolated yield of α-hydroxyphosphinate 4a.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

C
J. Dussart et al.
Paper
Synthesis
1 (1JPH = 568.1 Hz) and a doublet for 2 (1JPH = 174.6 Hz), re-
spectively. After the addition of benzaldehyde (3a), the
bis(trimethylsilyl)phosphonite (2) signal disappeared in fa-
vor of a new signal at 22.1 ppm [P(V) area] correlated to the
silylated α-hydroxyphosphinate 5 formation. After hydroly-
sis, 31P NMR signal shifted to 26.7 ppm corresponding to 4a.
This signal multiplicity is an expected doublet of doublets
cessfully led to the expected α-hydroxyphosphinates 4b–d,
albeit a lower yield was obtained starting from the 2-chlo-
robenzaldehyde (3b) probably due to the steric hindrance.
As a general trend, the substitution of an electron-donating
group at the para-position of benzaldehyde by an electron-
withdrawing group provided the α-hydroxyphosphinates
4f–h in similar excellent yields (85–98%).
However, when the reaction was carried out with hypo-
phosphorous acid (1) and m-nitrobenzaldehyde (3i), the
corresponding α-hydroxyphosphinate 4i was obtained in a
lower yield of 49%. Moreover, the reaction was also success-
ful even in the presence of bulkier aromatic and heteroaro-
matic aldehydes 3j–o and gave the α-hydroxyphosphinates
4j–o in good to excellent yields (60 to 100%).
2
(1JPH = 517.2 Hz; JPH = 8.7 Hz). It was noted that a small
quantity of silylated phosphorous acid 6 was detected at –
14.1 ppm probably due to the bis(trimethylsilyl)phos-
phonite (2) oxidation leading to the disodium salt 7. As pre-
viously mentioned, we never detected any signal corre-
sponding to the symmetrically disubstituted phosphinate
formation even in excess of BSA.8,10h
Under these optimized conditions, the scope of the
Abramov reaction was studied on various aromatic and al-
kyl substituted aldehydes (Scheme 3). Most of the reactions
were almost complete after only 30 minutes to afford sodi-
um α-hydroxyphosphinates 4a–v after simple washes in
good to excellent yields (60 to 99%). The introduction of
halogen on ortho- or para- positions of benzaldehyde suc-
We then performed the reaction between various alkyl
aldehydes 3p–v and hypophosphorous acid (1) in the pres-
ence of BSA under the optimized conditions. Remarkably,
the reaction was successful in the presence of challenging
aldehydes like formaldehyde (3p) and acetaldehyde (3q). In
the first case, the gaseous formaldehyde, in situ generated
by depolymerization of paraformaldehyde,14 was bubbled
Figure 1 31P{1H} (in red) and 31P (in blue) NMR monitoring of the Abramov reaction between hypophosphorous acid (1; 1 equiv) and benzaldehyde
(3a; 1 equiv) in the presence of BSA (2 equiv)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

D
J. Dussart et al.
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Synthesis
2) R
3a–v
CH2Cl2, 0 °C, 20–35 min
, (1 equiv)
O
1) BSA (2 equiv)
CH2Cl2, 0 °C, 40 min
O
P
O
P
R
2
O
Na
H
OH
H
3) NaOH (aq, 0.5 M)
H
OH
1
4a–v
MeO
O Na
F
Cl
O
O
P
O
P
O
O
P
P
P
O Na
O Na
O Na
O Na
H
H
H
H
H
OH
OH
Cl
OH
OH
OH
4e, 25 min, 98%
4a, 20 min, 96%
4b, 25 min, 68%
MeOOC
O Na
4c, 30 min, 99%
4d, 20 min, 83%
F3C
NC
O Na
O
O
O
P
O
P
O
P
P
H
P
O Na
O Na
O Na
O2N
H
H
H
H
OH
OH
OH
OH
OH
4f, 30 min, 95%
4g, 35 min, 90%
4h, 20 min, 85%
4i, 30 min, 49%
4j, 30 min, 64%
O
P
O
P
O
O
P
O
P
O Na
P
O Na
O Na
O Na
S
N
H
H
H
H
OH
O Na
OH
OH
OH
H
4k, 25 min, 75%
4l, 25 min, 100%
4n, 20 min, 100%
4o, 20 min, 85%
OH
4m, 20 min, 60%
O
O
O
P
O
P
O
O
P
O
P
P
P
H
P
O Na
O Na
O Na
O Na
O Na
O Na
O Na
3
H
H
H
H
H
H
OH
OH
OH
OH
OH
OH
OH
4p, 25 min, 36 % 4q, 20 min, 91% 4r, 25 min, 86%
4s, 25 min, 82%
4t, 30 min, 75%
4u, 25 min, 84%
4v, 30 min, 80%
Scheme 3 Scope of aldehydes
through the phosphonite solution at 0 °C under an argon
flux. The reaction conversion did not exceed 45% even after
extended time. However, the corresponding α-hydroxy-
phosphinate 4p was still isolated in a yield of 36%. This sig-
nificant and unoptimized result is the first example for the
synthesis of (1-hydroxymethyl)phosphinate (4p) under
mild conditions. Indeed, only few work reported the syn-
thesis of 4p under harsh conditions and long reaction
time.15 It was also noted that the reaction conversion was
quite low in the presence of paraformaldehyde (<5%) even
after extended time and refluxing. When the reaction was
conducted in the presence of volatile acetaldehyde, the cor-
responding silylated α-hydroxyphosphinate was formed af-
ter only 20 minutes. The expected α-hydroxyphosphinate
4q was then isolated in an excellent yield of 91%. The other
aliphatic aldehydes 3r–v also allowed to achieve the reac-
tion in very good yields (75–86%). It is important to notice
that we never detected any side-product resulting from the
α-hydrogen elimination on aliphatic aldehydes compared to
previous reported work.10a
(51–97%). The Abramov reaction between acetophenone
(8a) and hypophosphorous acid (1) in the presence of BSA
as a silylating agent gave the desired α-hydroxyphosphinate
9a in an excellent yield (97%). para-Substituted halogenoac-
etophenones 8b,c also furnished the products 9b,c in 3
hours. In addition, it was noted that the introduction of a
chlorine on meta- and ortho-positions of acetophenone al-
lowed to dramatically reduce the reaction time to 1.5 hours
and 15 minutes, respectively, in similar yields (75 and 85%).
The α-hydroxyphosphinate 9f substituted by a trifluoro-
methyl group was successfully obtained only after 15 min-
utes in 91% yield while we observed a slower reaction rate
in the presence of 4-methoxyacetophenone (8g). Further-
more, we unsurprisingly found that the replacement of a 3-
methyl group (8h, 9h) by a 2-methyl moiety (8i, 9i) on ace-
tophenone doubled the reaction time. Finally, the reaction
was also successfully conducted in the presence of bulkier
ketones such as benzophenone (8j) and tetralone (8k) and
led to the desired α-hydroxyphosphinates 9j,k in moderate
yields (51 and 55%) involving longer reaction times.
Thereafter, the same mild reaction conditions were test-
ed on various ketones as electrophile in order to enlarge the
scope of the reaction (Scheme 4). As a general trend, the re-
action rates are slower in the presence of ketones than alde-
hydes. For the range of studied ketones, the reactions were
complete after 1.5–18 hours. After purification, the corre-
sponding sodium salts were obtained in rather good yields
In conclusion, we have proposed a general protocol for
the equimolar Abramov reaction between carbonyl com-
pounds and hypophosphorous acid (1) in the presence of
only 2 equivalents of BSA as a silylating agent. This general
method has been successfully applied to various substitut-
ed aliphatic and aromatic aldehydes and ketones leading to
easily purified H-α-hydroxyphosphinates in good to excel-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

E
J. Dussart et al.
Paper
Synthesis
R2
R1
8a–k
O
2)
, (1 equiv)
1) BSA (2 equiv)
CH2Cl2, 0 °C, 40 min
O
P
O
P
CH2Cl2, 0 °C, 15 min–18 h
R1
R2
2
O
Na
H
OH
H
3) NaOH (aq, 0.5 M)
H
OH
1
9a–k
F
Cl
O
P
O
O
P
P
O
Na
O
Na
O
Na
H
H
H
OH
OH
OH
Me
Me
Me
9c, 3 h, 80%
9b, 3 h, 82%
9a, 4 h, 97%
Cl
Cl
F3C
MeO
O
P
O
P
O
P
O
P
O
Na
O
Na
O
Na
O
Na
H
H
H
H
OH
OH
OH
OH
Me
Me
Me
Me
9d, 1.5 h, 75%
9e, 15 min, 85%
9g, 6.5 h, 61%
9f, 15 min, 91%
O
O
Me
O
O
P
HO
P
O
O
Na
Na
P
H
P
H
O
Na
O
Na
Me
OH
H
H
OH
Me
OH
Me
9h, 3 h, 91%
9i, 6 h, 74%
9j, 6 h, 55%
9k, 18 h, 51%
Scheme 4 Scope of ketones
lent yields and shorter reaction times than those reported
methods.10 Moreover, the reaction is also effective in the
presence of challenging aldehydes such as formaldehyde
and acetaldehyde. Furthermore, symmetrically disubstitut-
ed phosphinates were not formed nor even detected unlike
the previous reported work.8,10g Current efforts are now fo-
cused on testing this methodology to other electrophiles
and this will be reported in due course.
with D1 = 2 s and 128 scans. The reactions were followed by 31P and
31P{1H} NMR experiments (the spectra were recorded without lock
and shims). High-resolution mass spectra (HRMS) were performed on
a Bruker maXis mass spectrometer in negative (ESI-) mode by the
‘Fédération de Recherche’ ICOA/CBM (FR2708) platform. MS analyses
were performed using
a Q-TOF Impact HD mass spectrometer
equipped with the electrospray (ESI) ion source (Bruker Daltonics).
The instrument was operated in the negative mode with an ESI
source on a Q-TOF mass spectrometer with an accuracy tolerance of 2
ppm. Samples were diluted with MeCN and H2O (15:85) and were an-
alyzed by mass spectrometry in continuous infusion using a syringe
pump at 200 μL/min. The mass profiles obtained by ESI-MS were ana-
lyzed using DataAnalysis software (Bruker Daltonics). IR spectra were
recorded on a ThermoFisher scientific Nicolet 380 FT-IR spectropho-
tometer. Smart OMNI-Sampler Germanium ATR Sampling accessory
was used. The Smart OMNI-Sampler utilized an extremely rugged
germanium ATR crystal. The wave numbers were expressed in cm–1
and comprised between 4000 and 675 cm–1. The samples were ana-
lyzed neat. The following abbreviations were used for IR spectra to in-
dicate the signal intensities: w (weak), m (medium), s (strong), br
(broad).
Reagents were purchased from common commercial suppliers (Sig-
ma-Aldrich, Alfa Aesar, Acros Organics) and used as delivered. All sol-
vents were extra-dried grade prior used. BSA was purchased from
Alfa Aesar (LOT: J24T014). Anhyd H3PO2 was prepared from commer-
cial aq H3PO2 solution (50% w/w) according to the procedure reported
by Montchamp et al.16 Reactions requiring inert conditions were car-
ried out in flame-dried glassware under an argon atmosphere.
NMR spectra were recorded at 20 °C on a Bruker Avance III 400 spec-
trometer (1H: 400 MHz, 13C: 101 MHz, 31P: 162 MHz, 19F: 377 MHz).
Chemical shifts (δ) are given in ppm, the number of protons (n) for a
given resonance was indicated by nH, and coupling constants J in Hz.
1H NMR spectra were calibrated on non-deuterated solvent residual
peak (H2O: 4.79 ppm) while H3PO4 (85% in H2O) was used as an exter-
nal standard for 31P NMR notably for the monitoring of the Abramov
reaction. Standard abbreviations were used for 1H, 13C, 31P and 19F
NMR spectra to indicate the signal multiplicity. All 13C NMR spectra
were measured with 1H-decoupling while 31P and 19F NMR spectra
were measured with 1H coupling (zoom on the spectrum) and 1H de-
coupling. 1H experiments with H2O presaturation were performed
One-Pot Abramov Reaction, Method A (Table 1); General Proce-
dure
To a dry and argon flushed 100 mL three-necked flask equipped with
a thermometer, an argon inlet, and an addition funnel, were succes-
sively introduced anhyd H3PO2 (1; 0.660 g, 10.0 mmol) and anhyd
CH2Cl2 (2 mL) under an argon atmosphere. BSA (6.11 g, 30.0 mmol)
was added dropwise at 0 °C under argon and the mixture was stirred
for 40 min. The reaction conversion was monitored by 31P NMR spec-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

F
J. Dussart et al.
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Synthesis
3
troscopy. To another dry and argon flushed 100 mL three-necked
flask equipped with a thermometer, an argon inlet, and an addition
funnel, were successively introduced the respective aldehyde 3 (10.0
mmol) and anhyd CH2Cl2 (2 mL). The bis(trimethylsilyl)phosphonite
solution prepared as above was added dropwise at 0 °C to the alde-
hyde solution. The reaction was monitored by 31P NMR spectroscopy.
The reaction mixture was quenched by adding aq 0.5 M NaOH (10 mL)
to adjust the pH value to 7.0. Then, CH2Cl2 was evaporated under re-
duced pressure and the solution was lyophilized. The crude residue
was washed with MeOH (H3PO3 removal) and EtOH (acetamide re-
moval) to give the product as a pure solid.
1H NMR (400 MHz, D2O): δ = 7.48 (d, JHH = 7.7 Hz, 1 H, H7), 7.42 (d,
3JHH = 7.9 Hz, 1 H, H4), 7.35 (t, 3JHH = 7.4 Hz, 1 H, H6), 7.32–7.24 (m, 1 H,
H5), 6.85 (d, 1JPH = 521.7 Hz, PH), 5.20 (d, 2JPH = 9.7 Hz 1 H, PCH).
13C NMR (101 MHz, D2O): δ = 135.6 (C2), 132.4 (d, JPC = 6.2 Hz, C3),
3
129.5 (C5), 129.2 (d, 4JPC = 2.4 Hz, C4), 128.6 (d, 3JPC = 4.9 Hz, C7), 127.4
(d, 5JPC = 2.0 Hz, C6), 70.2 (d, 1JPC = 104.2 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 25.8 (s).
31P NMR (162 MHz, D2O): δ = 25.8 (dd, 1JPH = 521.7 Hz, 2JPH = 9.7 Hz).
These data are in agreement with those previously reported by
Kaboudin et al.17
Optimized Method B for the Synthesis of α-Hydroxyphosphinate
Sodium Salts 4a–v and 9a–k
[(4-Fluorophenyl)(hydroxy)methyl]phosphinate Sodium Salt (4c)
White powder; yield: 2.10 g (99%).
To a dry and argon flushed 100 mL three-necked flask equipped with
a thermometer, an argon inlet, and an addition funnel, were succes-
sively introduced anhyd H3PO2 (1; 0.660 g, 10.0 mmol) and anhyd
CH2Cl2 (2 mL) under an argon atmosphere. BSA (4.07 g, 20.0 mmol)
was added dropwise at 0 °C under argon and the mixture was stirred
for 40 min. The reaction conversion was monitored by 31P NMR spec-
troscopy. A solution of the respective aldehyde 3 or ketone 8 (10.0
mmol) in anhyd CH2Cl2 (2 mL) was added dropwise at 0 °C and the
reaction was monitored by 31P NMR spectroscopy. The mixture was
quenched by adding aq 0.5 M NaOH (10 mL) to adjust the pH value to
7.0. Then, CH2Cl2 was evaporated under reduced pressure and the
solution was lyophilized.
IR (neat): 3167w (O–H), 2988w (C–HAr), 2901w (C–H), 2322w (P–H),
1608w (C=CAr), 1511m (C-F), 1187s (P=O), 1067m (C–OH), 1022m (P–
O), 742w cm–1 (C–P).
1
1H NMR (400 MHz, D2O): δ = 7.47 (d, JPH = 517.6 Hz, PH), 7.42–7.34
(m, 2 H, H3, H7), 7.15 (t, 3JHH = 8.9 Hz, 2 H, H4, H6), 4.68 (d, 2JPH = 8.4 Hz,
1 H, PCH).
13C NMR (101 MHz, D2O): δ = 162.2 (dd, 1JFC = 243.2 Hz, 5JPC = 3.0 Hz,
C5), 133.1 (C2), 128.8 (dd, 3JFC = 8.4 Hz, 3JPC = 5.3 Hz, C3, C7), 115.2 (dd,
2JFC = 21.6 Hz, 4JPC = 2.0 Hz, C4, C6), 73.0 (d, 1JPC = 105.4 Hz, C1).
19F{1H} NMR (377 MHz, D2O): δ = –115.4 (d, 6JFP = 4.2 Hz).
19F NMR (377 MHz, D2O): δ = –115.3 to –115.5 (m).
31P{1H} NMR (162 MHz, D2O): δ = 26.2 (d).
Purification procedure for α-hydroxyphosphinate sodium salts 4a–o
and 4r–v: After lyophilization, the crude residue was washed with
MeOH (Na2HPO3 removal) and EtOH (acetamide removal) to give the
product as a pure solid.
31P NMR (162 MHz, D2O): δ = 26.2 (dm, 1JPH = 517.6 Hz).
MS (ESI–): m/z = 189.01 [M – H]–, 401.01 [2 M – 2 H + Na]–.
Purification procedure for α-hydroxyphosphinate sodium salts 9a–k:
After lyophilization, the crude solid was dissolved in a minimum vol-
ume of EtOH. When Et2O was slowly added to the resulting solution
cooled at 0 °C, a solid was formed. The pure solid was collected by fil-
tration.
HRMS (ESI–): m/z [M – H]– calcd for C7H7FO3P: 189.0122; found:
189.0122.
[(4-Chlorophenyl)(hydroxy)methyl]phosphinate Sodium Salt (4d)
White powder; yield: 1.89 g (83%).
IR (neat): 3159w (O–H), 2988w (C–HAr), 2901w (C–H), 2327w (P–H),
1492w (C=CAr), 1185s (P=O), 1068m (C–OH), 1021m (P–O), 829w (C–
Cl), 739w cm–1 (C–P).
[Hydroxy(phenyl)methyl]phosphinate Sodium Salt (4a)
White powder; yield: 1.86 g (96%).
IR (neat): 3181br (O–H), 2935w (C–HAr), 2901w (C–H), 2325w (P–H),
1498w (C=CAr), 1188s (P=O), 1061m (C–OH), 1019m (P–O), 731w cm–1
(C–P).
1H NMR (400 MHz, D2O): δ = 7.40 (d, 3JHH = 8.5 Hz, 2 H, H3, H7), 7.33 (d,
1
2
3JHH = 8.5 Hz, 2 H, H4, H6), 6.80 (d, JPH = 518.6 Hz, PH), 4.66 (d, JPH
=
8.8 Hz, 1 H, PCH).
1
1H NMR (400 MHz, D2O): δ = 6.85 (d, JPH = 516.0 Hz, PH), 7.47–7.33
2
13C NMR (101 MHz, D2O): δ = 135.9 (d, JPC = 3.2 Hz, C2), 132.9 (C5),
(m, 5 Harom), 4.69 (d, 2JPH = 8.0 Hz, 1 H, PCH).
128.5–128.4 (m, C3, C4, C6, C7), 73.1 (d, 1JPC = 104.5 Hz, C1).
13C NMR (101 MHz, D2O): δ = 137.3 (C2), 128.5 (d, 4JPC = 2.0 Hz, C4, C6),
31P{1H} NMR (162 MHz, D2O): δ = 25.9 (s).
31P NMR (162 MHz, D2O): δ = 25.9 (dd, 1JPH = 518.6 Hz, 2JPH = 8.8 Hz).
127.9 (d, 5JPC = 3.0 Hz, C5), 127.0 (d, 3JPC = 5.1 Hz, C3, C7), 73.8 (d, 1JPC
=
105.0 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 26.5 (s).
31P NMR (162 MHz, D2O): δ = 26.5 (dd, 1JPH = 516.0 Hz, 2JPH = 8.0 Hz).
These data are in agreement with those previously reported by
Kaboudin et al.17
These data are in agreement with those previously reported by
Kaboudin et al.17
[Hydroxy(4-methoxyphenyl)methyl]phosphinate Sodium Salt (4e)
White powder; yield: 2.19 g (98%).
IR (neat): 3167br (O–H), 2944w (C–HAr), 2834w (C–H), 2312w (P–H),
1670w (C=CAr), 1612w (C=CAr), 1245m (C–OMe), 1189s (P=O), 1069m
(C–OH), 1020m (P–O), 743w cm–1 (C–P).
[(2-Chlorophenyl)(hydroxy)methyl]phosphinate Sodium Salt (4b)
White powder; yield: 1.41 g (68%).
IR (neat): 3163w (O–H), 2933w (C–HAr), 2816w (C–H), 2367w (P–H),
1152s (P=O), 1022m (C–OH), 1013m (P–O), 743m (C–Cl), 705w cm–1
(C–P).
1H NMR (400 MHz, D2O): δ = 7.30 (d, 3JHH = 8.6 Hz, 2 H, H3, H7), 6.98 (d,
1
2
3JHH = 8.6 Hz, 2 H, H4, H6), 6.79 (d, JPH = 514.9 Hz, PH), 4.59 (d, JPH
=
8.1 Hz, 1 H, PCH), 3.79 (s, 3 H, OCH3).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

G
J. Dussart et al.
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Synthesis
13C NMR (101 MHz, D2O): δ = 158.5 (d, 5JPC = 2.5 Hz, C5), 129.6 (d, 2JPC
=
13C NMR (101 MHz, D2O): δ = 143.4 (C2), 132.4 (C4, C6), 127.2 (d, 3JPC
4.4 Hz, C3, C7), 119.8 (C8), 109.9 (d, JPC = 2.3 Hz, C5), 73.4 (d, JPC
101.5 Hz, C1).
=
=
3
4
5
1
31.5 Hz, C2), 128.5 (d, JPC = 5.5 Hz, C3, C7), 114.0 (d, JPC = 1.7 Hz, C4,
C6), 73.2 (d, 1JPC = 106.5 Hz, C1), 55.3 (OCH3).
31P{1H} NMR (162 MHz, D2O): δ = 26.5 (s).
31P{1H} NMR (162 MHz, D2O): δ = 25.1 (s).
31P NMR (162 MHz, D2O): δ = 26.5 (dd, 1JPH = 514.9 Hz, 2JPH = 8.1 Hz).
MS (ESI–): m/z = 201.03 [M – H]–, 425.05 [2 M – 2 H + Na]–.
31P NMR (162 MHz, D2O): δ = 25.1 (dd, 1JPH = 523.8 Hz, 2JPH = 9.5 Hz).
MS (ESI–): m/z = 196.02 [M – H]–, 415.02 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C8H10O4P: 201.0322; found:
HRMS (ESI–): m/z [M – H]– calcd for C8H7NO3P: 196.0169; found:
201.0322.
196.0168.
{Hydroxy[4-(trifluoromethyl)phenyl]methyl}phosphinate Sodi-
um Salt (4f)
[Hydroxy(3-nitrophenyl)methyl]phosphinate Sodium Salt (4i)
Brown powder; yield: 2.29 g (49%).
White powder; yield: 2.48 g (95%).
IR (neat): 3145w (O–H), 2988w (C–HAr), 2901w (C–H), 2332w (P–H),
1667w (C=CAr), 1526m (C–NO2), 1356m (C–NO2), 1190m (P=O), 1060s
(C–OH), 1019m (P–O), 751w cm–1 (C–P).
IR (neat): 3165w (O–H), 2987w (C–HAr), 2325w (P–H), 1621w (C=CAr),
1324m (C–F), 1188m (P=O), 1067s (C–OH), 1018m (P–O), 759w cm–1
(C–P).
1H NMR (400 MHz, D2O): δ = 8.21 (s, 1 H, H7), 8.15 (d, 3JHH = 8.1 Hz, 1
1H NMR (400 MHz, D2O): δ = 7.60 (d, 3JHH = 7.9 Hz, 2 H, H4, H6), 7.41 (d,
H, H5), 7.74 (d, JHH = 7.5 Hz, 1 H, H3), 7.59 (t, JHH = 8.1 Hz, 1 H, H4),
3
3
3JHH = 7.9 Hz, 2 H, H3, H7), 6.71 (d, JPH = 521.4 Hz, PH), 4.66 (d, JPH
=
6.86 (d, 1JPH = 523.1 Hz, PH), 4.83 (d, 2JPH = 8.7 Hz, 1 H, PCH).
1
2
8.8 Hz, 1 H, PCH).
13C NMR (101 MHz, D2O): δ = 141.6 (C2), 129.0 (dd, 2JFC = 32.1 Hz, 5JPC
13C NMR (101 MHz, D2O): δ = 147.9 (C6), 139.4 (C2), 133.4 (d, 3JPC = 4.7
Hz, C3), 129.5 (d, 4JPC = 2.1 Hz, C4), 122.7 (d, 5JPC = 2.6 Hz, C5), 121.5 (d,
3JPC = 4.9 Hz, C7), 72.9 (d, 1JPC = 102.7 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 25.0 (s).
31P NMR (162 MHz, D2O): δ = 25.0 (dd, 1JPH = 523.1 Hz, 2JPH = 8.7 Hz).
MS (ESI–): m/z = 216.01 [M – H]–, 152.04 [M – H – HPO2]–.
=
3
2.9 Hz, C5), 127.2 (d, JPC = 4.9 Hz, C3, C7), 125.4–125.1 (m, C4, C6),
124.3 (q, 1JFC = 271.2 Hz, C8), 73.4 (d, 1JPC = 102.6 Hz, C1).
19F{1H} NMR (377 MHz, D2O): δ = –62.29 (s).
19F NMR (377 MHz, D2O) δ = –62.29 (s).
31P{1H} NMR (162 MHz, D2O): δ = 25.6 (s).
31P NMR (162 MHz, D2O): δ = 25.6 (dd, 1JPH = 521.4 Hz, 2JPH = 8.8 Hz).
MS (ESI–): m/z = 239.01 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C7H7NO5P: 216.0067; found:
216.0068.
[Hydroxy(mesityl)methyl]phosphinate Sodium Salt (4j)
HRMS (ESI–): m/z [M – H]– calcd for C8H7F3O3P: 239.0090; found:
239.0090.
White powder; yield: 1.51 g (64%).
IR (neat): 3172w (O–H), 2948w (C–HAr), 2910w (C–H), 2317w (P–H),
1670w (C=CAr), 1611w (C=CAr), 1394w (CH3), 1170m (P=O), 1100w
(C–O), 1060s (C–OH), 1041m (P–O), 743w cm–1 (C–P).
{Hydroxy[4-(methoxycarbonyl)phenyl]methyl}phosphinate Sodi-
um Salt (4g)
White powder; yield: 2.14 g (90%).
1H NMR (400 MHz, D2O): δ = 7.31 (dd, 1JPH = 517.3, 3JHH = 2.8 Hz, PH),
6.92 (s, 2 H, H4, H6), 5.06 (dd, JPH = 16.4 Hz, JHH = 2.8 Hz, 1 H, PCH),
2.33 (s, 6 H, 8-CH3, 9-CH3), 2.20 (s, 3 H, 10-CH3).
2
3
IR (neat): 3165w (O–H), 2957w (C–HAr), 2911w (C–H), 2320w (P–H),
1725m (C=O), 1611w (C=CAr), 1281m (C–O), 1187s (P=O), 1110m (C–
O), 1071m (C–OH), 1024m (P–O), 748w cm–1 (C–P).
Water presaturation 1H NMR (400 MHz, D2O): δ = 7.99 (d, JHH = 8.2
2
13C NMR (101 MHz, D2O): δ = 137.8 (C5), 137.7 (d, JPC = 4.7 Hz, C2),
1
131.1 (C3, C7), 129.6 (C4, C6), 71.5 (d, JPC = 105.2 Hz, C1), 20.5 (8-CH3,
3
9-CH3), 19.9 (10-CH3).
1
Hz, 2 H, H4, H6), 7.57–7.40 (m, 2 H, H3, H7), 6.82 (d, JPH = 521.8 Hz,
PH), 4.78 (d, 2JPH = 9.1 Hz, 1 H, PCH), 3.88 (s, 3 H, CO2CH3).
31P{1H} NMR (162 MHz, D2O): δ = 25.9 (s).
31P NMR (162 MHz, D2O): δ = 25.9 (dd, 1JPH = 517.3 Hz, 2JPH = 16.3 Hz).
MS (ESI–): m/z = 213.07 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C10H14O3P: 213.0686; found:
213.0685.
13C NMR (101 MHz, D2O): δ = 169.2 (C8), 143.2 (C2), 129.4 (C4, C6),
128.6 (C5), 126.8 (C3, C7), 73.5 (d, 1JPC = 102.3 Hz, C1), 52.5 (CO2CH3).
31P{1H} NMR (162 MHz, D2O): δ = 25.6 (s).
31P NMR (162 MHz, D2O): δ = 25.6 (dd, 1JPH = 521.8 Hz, 2JPH = 9.1 Hz).
MS (ESI–): m/z = 229.03 [M – H]–.
[Hydroxy(naphthalen-1-yl)methyl]phosphinate Sodium Salt (4k)
HRMS (ESI–): m/z [M – H]– calcd for C9H10O5P: 229.0271; found:
229.0272.
White powder; yield: 1.83 g (75%).
IR (neat): 3687w (O–H), 3172w (O–H), 2988w (C–HAr), 2900w (C–H),
2372w (P–H), 1596w (C=CAr), 1147s (P=O), 1083m (C–OH), 1041m
(P–O), 744m cm–1 (C–P).
[(4-Cyanophenyl)(hydroxy)methyl]phosphinate Sodium Salt (4h)
White powder; yield: 2.14 g (85%).
1H NMR (400 MHz, D2O): δ = 8.15 (d, 3JHH = 8.0 Hz, 1 H, H5) 7.99–7.92
IR (neat): 3188w (O–H), 2978w (C–HAr), 2903w (C–H) 2324w (P–H),
2239w (C≡N), 1671w (C=CAr), 1611w (C=CAr), 1187s (P=O), 1068m (C–
OH), 1022m (P–O), 750w cm–1 (C–P).
(m, 1 H, H7 or H10), 7.89 (d, 3JHH = 8.2 Hz, 1 H, H7 or H10), 7.70–7.63 (m,
1 H, H3), 7.63–7.51 (m, 3 H, H4, H8, H9) 6.93 (dd, 1JPH = 519.4 Hz, 4JPH
1.9 Hz, PH), 5.53 (d, 2JPH = 10.1 Hz, 1 H, PCH).
=
3
Water presaturation 1H NMR (400 MHz, D2O): δ = 7.75 (d, JHH = 8.0
Hz, 2 H, H4, H6), 7.51 (d, 3JHH = 7.0 Hz, 2 H, H3, H7), 6.82 (d, 1JPH = 523.8
Hz, PH), 4.79 (d, 2JPH = 9.7 Hz, 1 H, PCH).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

H
J. Dussart et al.
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Synthesis
13C NMR (101 MHz, D2O): δ = 133.7 (C2), 133.4 (C6), 130.6 (d, 3JPC = 4.3
31P NMR (162 MHz, D2O): δ = 24.6 (dd, 1JPH = 520.8, 2JPH = 9.0 Hz).
MS (ESI–): m/z = 176.98 [M – H]–, 376.94 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C5H6O3PS: 176.9781; found:
176.9781.
4
Hz, C11), 128.6 (C7), 128.1 (d, JPC = 2.9 Hz, C10), 126.3, 126.0 (C8, C9),
4
3
125.7 (d, JPC = 2.8 Hz, C4), 124.9 (d, JPC = 6.4 Hz, C3), 123.8 (C5), 70.4
(d, 1JPC = 104.4 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 26.8 (s).
31P NMR (162 MHz, D2O): δ = 26.8 (dd, 1JPH = 519.4 Hz, 2JPH = 10.1 Hz).
[Hydroxy(pyridin-2-yl)methyl]phosphinate Sodium Salt (4o)
These data are in agreement with those previously reported by
Kaboudin et al.17
White powder; yield: 1.66 g (85%).
IR (neat): 3151w (O–H), 2989w (C–HAr), 2911w ( C–H), 2345w (P–H),
1591w (C=CAr), 1193s (P=O), 1068m (C–OH), 1026s (P–O), 744w cm–1
(C–P) .
[Hydroxy(naphthalen-2-yl)methyl]phosphinate Sodium Salt (4l)
White powder; yield: 2.44 g (100%).
1H NMR (400 MHz, D2O): δ = 8.46 (d, 3JHH = 4.6 Hz, 1 H, H6), 7.86 (t, 3JHH
=
IR (neat): 3172w (O–H), 2988w (C–HAr), 2900w (C–H), 2372w (P–H),
1596w (C=CAr), 1147s (P=O), 1083m (C–OH), 1041m (P–O), 744m cm–1
(C–P).
1H NMR (400 MHz, D2O): δ = 7.99–7.84 (m, 4 H, H4, H11, H9, H6), 7.60–
7.46 (m, 3 H, H3, H7, H8), 6.88 (d, 1JPH = 518.1 Hz, PH), 4.85 (d, 2JPH = 8.4
Hz, 1 H, PCH).
7.7 Hz 1 H, H4), 7.47 (d, 3JHH = 7.9 Hz, 1 H, H3), 7.39–7.31 (m, 1 H, H5),
6.88 (d, 1JPH = 525.7 Hz, PH), 4.76 (d, 2JPH = 9.8 Hz, 1 H, PCH).
31P{1H} NMR (162 MHz, D2O): δ = 25.3 (s).
31P NMR (162 MHz, D2O): δ = 25.3 (dd, 1JPH = 525.7 Hz, 2JPH = 9.8 Hz).
MS (ESI–): m/z = 172.02 [M – H]–, 367.02 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C6H7NO3P: 172.0169; found:
172.0170.
13C NMR (101 MHz, D2O): δ = 135.1 (C2), 132.9 (d, JPC = 2.0 Hz, C10),
4
132.6 (d, 5JPC = 1.6 Hz, C5), 128.0 (d, 4JPC = 1.3 Hz C4), 127.9, 127.6 (C6,
C9), 126.5, 126.2 (C7, C8), 125.6 (d, 3JPC = 6.6 Hz, C11), 125.1 (d, 3JPC = 4.1
Hz, C3), 73.9 (d, 1JPC = 104.4 Hz, C1).
(1-Hydroxymethyl)phosphinate Sodium Salt (4p)
To a dry and argon flushed 100 mL three-necked flask equipped with
a thermometer, an argon inlet, and an addition funnel, were succes-
sively introduced anhyd H3PO2 (1; 0.660 g, 10.0 mmol) and anhyd
CH2Cl2 (2 mL) under an argon atmosphere. BSA (4.07 g, 20.0 mmol)
was added dropwise at 0 °C under argon and the mixture was stirred
for 40 min. The reaction conversion was monitored by 31P NMR spec-
troscopy. Gaseous formaldehyde generated by heating paraformalde-
hyde was bubbled via a cannula into the cooled silylated phosphonite
solution for 25 min under an argon flux. The reaction was monitored
by 31P NMR spectroscopy. The reaction mixture was quenched by
adding aq 0.5 M NaOH (10 mL) to adjust the pH value to 7.0. Then,
CH2Cl2 was evaporated under reduced pressure and the solution was
lyophilized. After lyophilization, the crude residue was washed with
EtOH (acetamide removal). After trituration of the solid with MeOH,
the mixture was filtered (NaH2PO2 partial removal) and the filtrate
was evaporated in vacuo. The resulting colorless oil was triturated
with ethanol until the formation of a precipitate (Na2HPO3 removal).
The supernatant was collected and finally evaporated in vacuo to af-
ford a colorless oil; yield: 0.483 g (36%, purity = 88%).
31P{1H} NMR (162 MHz, D2O): δ = 26.4 (s).
31P NMR (162 MHz, D2O): δ = 26.4 (dd, 1JPH = 518.1 Hz, 2JPH = 8.4 Hz).
MS (ESI–): m/z = 221.04 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C11H10O3P: 221.0373; found:
221.0374.
[Anthracen-9-yl(hydroxy)methyl]phosphinate Sodium Salt (4m)
Yellow powder; yield: 1.77 g (60%).
IR (neat): 3161w (O–H), 2930w (C–HAr), 2923w (C–H), 2347w (P–H),
1675m (C=C), 1622w (C=CAr), 1590w (C=CAr), 1580w (C=CAr), 1187w
(P=O), 1069w (C–OH), 1050w (P–O), 730m cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 8.63–8.36 (m, 3 H, H9, H4, H14), 8.02 (d,
3JHH = 8.1 Hz, 2 H, H7, H11), 7.53–7.41 (m, 4 H, H5, H6, H12, H13), 7.25 (d,
1JPH = 522.5 Hz, PH), 6.10 (d, 2JPH = 16.3 Hz, 1 H, PCH).
13C NMR (101 MHz, D2O): δ = 137.7 (C2), 131.4 (C8, C10), 130.0 (d, 3JPC
=
5.1 Hz, C3, C15), 129.2, 129.1 (C7, C11), 128.5 (C4, C14), 126.2 (C9), 125.3
(C5, C6, C12, C13), 70.8 (d, 1JPC = 104.4 Hz, C1).
IR (neat): 3169w (O–H), 2960w (C–H), 2917w (C–H), 2308w (P–H),
1168s (P=O), 1048m (C–OH), 1039m (P–O), 756w cm–1 (C–P).
31P{1H} NMR (162 MHz, D2O): δ = 25.3 (s).
31P NMR (162 MHz, D2O): δ = 25.3 (dd, 1JPH = 522.5 Hz, 2JPH = 16.3 Hz).
MS (ESI–): m/z = 271.05 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C15H12O3P: 271.0530; found:
271.0530.
1
3
1H NMR (400 MHz, D2O): δ = 6.93 (dt, JPH = 511.2 Hz, JHH = 2.3 Hz,
PH), 3.59 (dd, 2JPH = 6.1 Hz, 3JHH = 2.3 Hz, 2 H, PCH2).
13C NMR (101 MHz, D2O): δ = 60.9 (d, 1JPC = 106.8 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 24.5 (s).
31P NMR (162 MHz, D2O): δ = 24.5 (dt, 1JPH = 511.2 Hz, 2JPH = 6.1 Hz).
[Hydroxy(thiophen-2-yl)methyl]phosphinate Sodium Salt (4n)
These data are in agreement with those previously reported by
Cristau et al.15b
White powder; yield: 2.00 g (100%).
IR (neat): 3157w (O–H), 2984w (C–HAr), 2905w (C–H), 2326w (P–H),
1196s (P=O), 1070m (C–OH), 1023m (P–O), 727w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 7.41 (d, 3JHH = 5.0 Hz, 1 H, H5), 7.12–7.07
(m, 1 H, H3), 7.07–7.03 (m, 1 H, H4), 6.86 (d, 1JPH = 520.8 Hz, PH), 4.90
(d, 2JPH = 9.0 Hz, 1 H, PCH).
(1-Hydroxyethyl)phosphinate Sodium Salt (4q)
After lyophilization, the crude residue was dissolved in a minimum
amount of H2O and washed several times with EtOAc (acetamide re-
moval). The aqueous layer was evaporated to give a colorless oil;
yield: 1.20 g (91%).
13C NMR (101 MHz, D2O): δ = 139.8 (C2), 127.2 (d, JPC = 1.8 Hz, C4),
4
4
3
1
126.1 (d, JPC = 2.5 Hz, C5), 126.0 (d, JCP = 6.9 Hz, C3), 69.5 (d, JPC
=
IR (neat): 3170w (O–H), 2963w (C–H), 2915w (C–H), 2310w (P–H),
1170s (P=O), 1050m (C–OH), 1040m (P–O), 757w cm–1 (C–P).
108.7 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 24.6 (s).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

I
J. Dussart et al.
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Synthesis
1
3
1H NMR (400 MHz, D2O): δ = 6.73 (dd, JPH = 505.7 Hz, JHH = 1.5 Hz,
PH), 3.70 (qdd, 3JHH = 7.1 Hz, 2JPH = 2.7 Hz, 3JHH = 1.5 Hz, 1 H, PCH), 1.29
(dd, 3JPH = 16.6 Hz, 3JHH = 7.1 Hz, 3 H, CH3).
31P NMR (162 MHz, D2O): δ = 28.5 (dm, 1JPH = 507.1 Hz).
MS (ESI–): m/z = 137.04 [M – H]–, 297.06 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C4H10O3P: 137.0373; found:
13C NMR (101 MHz, D2O): δ = 66.2 (d, 1JPC = 109.7 Hz, C1), 14.7.
31P{1H} NMR (162 MHz, D2O): δ = 30.2 (s).
137.0371.
31P NMR (162 MHz, D2O): δ = 30.2 (dqd, 1JPH = 505.7 Hz, 3JPH = 16.6 Hz,
2JPH = 2.7 Hz).
(1-Hydroxy-2,2-dimethylpropyl)phosphinate Sodium Salt (4u)
White powder; yield: 1.46 g (84%).
These data are in agreement with those previously reported by David
et al.18
IR (neat): 3278br (O–H), 2953w (C–H), 2867w (C–H), 2326w (P–H),
1186s (P=O), 1058s (C–OH), 1026m (P–O), 738w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 6.87 (d, 1JPH = 508.3 Hz, PH), 3.17 (d, 2JPH
6.8 Hz, 1 H, PCH), 0.98 (s, 9 H, t-C4H9).
=
(1-Hydroxypropyl)phosphinate Sodium Salt (4r)
White powder; yield: 1.17 g (86%).
13C NMR (101 MHz, D2O): δ = 78.4 (d, 1JPC = 105.7 Hz, C1), 33.8 (d, 2JPC
3.3 Hz, C2), 25.9 [d, 3JPC = 5.6 Hz, C(CH3)3].
31P{1H} NMR (162 MHz, D2O): δ = 27.3 (s).
31P NMR (162 MHz, D2O): δ = 27.3 (dd, 1JPH = 508.3 Hz, 2JPH = 6.8 Hz).
MS (ESI–): m/z = 151.05 [M – H]–, 325.09 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C5H12O3P: 151.0529; found:
=
IR (neat): 3171w (O–H), 2962w (C–H), 2915w (C–H), 2309w (P–H),
1169s (P=O), 1049m (C–OH), 1040m (P–O), 758w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 6.74 (d, JPH = 520.7 Hz, PH), 3.49–3.39
1
(m, 1 H, PCH), 1.75–1.65 (m, 1 H, H2a), 1.61–1.45 (m, 1 H, H2b), 1.00 (t,
3JHH = 7.4 Hz, 3 H, CH3).
13C NMR (101 MHz, D2O): δ = 72.1 (d, 1JPC = 110.0 Hz, C1), 22.5 (d, 2JPC
3.7 Hz, C2), 9.8 (d, 3JPC = 12.1 Hz, C3).
=
151.0528.
31P{1H} NMR (162 MHz, D2O): δ = 29.2 (s).
31P NMR (162 MHz, D2O): δ = 29.2 (dm, 1JPH = 505.4 Hz).
[Cyclohexyl(hydroxy)methyl]phosphinate Sodium Salt (4v)
White powder; yield: 1.6 g (80%).
MS (ESI–): m/z = 123.02 [M – H]–, 269.03 [2 M – 2 H + Na]–, 415.04 [3
IR (neat): 3235br (O–H), 2921w (C–H), 2852w (C–H), 2303w (P–H),
1173s (P=O), 1076m (C–OH), 1037m (P–O), 745w cm–1 (C–P).
M – 3 H + 2 Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C3H8O3P: 123.0216; found:
123.0216.
1
3
1H NMR (400 MHz, D2O): δ = 6.86 (dd, JPH = 507.1 Hz, JHH = 1.1 Hz,
PH), 3.29 (br t, 2JPH = 5.9 Hz, 1 H, PCH ), 1.89–1.79 (m, 1 H, H3a or H7a),
1.79–1.65 (m, 4 H, H2, H4a, H6a H3a or H7a), 1.65–1.55 (m, 1 H, H5a),
1.33–1.03 (m, 5 H, H5b, H4b H6b, H3b, H7b).
(1-Hydroxypentyl)phosphinate Sodium Salt (4s)
White powder; yield: 1.43 g (82%).
13C NMR (101 MHz, D2O): δ = 75.1 (d, 1JPC = 108.5 Hz, C1), 38.9 (d, 2JPC
=
IR (neat): 3163w (O–H), 2953w (C–H), 2926w (C–H), 2854w (C–H),
2310w (P–H), 1168s (P=O), 1073m (C–OH), 1045m (P–O), 764w cm–1
(C-P) .
1H NMR (400 MHz, D2O): δ = 6.75 (br d, 1JPH = 503.8 Hz, PH), 3.59–3.48
(m, 1 H, PCH), 1.77–1.62 (m, 1 H, H2a), 1.62–1.44 (m, 2 H, H2b, H3a),
1.44–1.23 (m, 3 H, H3b, H4), 0.89 (t, 3JHH = 6.0 Hz, 3 H, CH3).
2.7 Hz, C2), 29.5, 28.0 (2 d, 3JPC = 7.4 Hz, C3, C7), 25.8, 25.7, 25.5 (C4, C5,
C6).
31P{1H} NMR (162 MHz, D2O): δ = 28.4 (s).
31P NMR (162 MHz, D2O): δ = 28.4 (dt, 1JPH = 507.1 Hz, 2JPH = 6.1 Hz).
MS (ESI–): m/z = 177.07 [M – H]–, 377.13 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C7H14O4P: 177.0686; found:
177.0685.
13C NMR (101 MHz, D2O): δ = 70.4 (d, 1JPC = 110.0 Hz, C1), 28.6 (d, 3JPC
3.0 Hz, C3), 27.2 (d, 2JPC = 12.1 Hz, C2), 21.7 (C4), 13.2 (C5).
=
31P{1H} NMR (162 MHz, D2O): δ = 29.6 (s).
31P NMR (162 MHz, D2O): δ = 29.6 (br d, 1JPH = 503.8 Hz).
MS (ESI–): m/z = 151.05 [M – H]–, 325.09 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C5H12O3P: 151.0529; found:
151.0530.
(1-Hydroxy-1-phenylethyl)phosphinate Sodium Salt (9a)
White powder; yield: 2.02 g (97%).
IR (neat): 3157w (O–H), 2973w (C–HAr), 2901w (C–H), 2320w (P–H),
1579w (C=CAr), 1171m (P=O), 1066w (C–OH), 1044 (P–O), 750w cm–1
(C–P).
1H NMR (400 MHz, D2O): δ = 7.52–7.45 (m, 2 H, H3, H7), 7.45– 7.38 (m,
2 H, H4, H6), 7.38–7.32 (m, 1 H, H5), 6.66 (d, 1JPH = 515.3 Hz, PH), 1.65
(d, 3JPH = 13.9 Hz, 3 H, CH3).
(1-Hydroxy-2-methylpropyl)phosphinate Sodium Salt (4t)
White powder; yield: 1.20 g (75%).
IR (neat): 3170br (O–H), 2956w (C–H), 2326w (P–H), 1180s (P=O),
1063m (C–OH), 1017m (P–O), 753w cm–1 (C–P).
13C NMR (101 MHz, D2O): δ = 141.4 (C2), 128.3 (d, 4JPC = 2.0 Hz, C4, C6),
127.3 (d, 5JPC = 2.5 Hz, C5), 125.8 (d, 3JPC = 3.9 Hz, C3, C7), 74.6 (d, 1JPC
106.4 Hz, C1), 21.6 (d, 2JPC = 6.2 Hz, CH3).
=
1
1H NMR (400 MHz, D2O): δ = 6.82 (d, JPH = 507.1 Hz, PH), 3.31–3.20
(m, 1 H, PCH), 2.07–1.92 (m, 1 H, H2), 0.96 (d, 3JHH = 7.6 Hz, 3 H, 3-CH3
31P{1H} NMR (162 MHz, D2O): δ = 31.0 (s).
31P NMR (162 MHz, D2O): δ = 31.0 (dq, 1JPH = 515.3 Hz, 3JPH = 13.9 Hz).
MS (ESI–): m/z = 185.04 [M – H]–, 393.06 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C8H10O3P: 185.0373; found:
185.0373.
or 4-CH3), 0.94 (d, 3JHH = 7.3 Hz, 3 H, 3-CH3 or 4-CH3).
1
13C NMR (101 MHz, D2O): δ = 75.6 (d, JPC = 108.7 Hz, C1), 29.0 (d, 2JPC
=
3.2 Hz, C2), 19.0 (d, 3JPC = 7.7 Hz, 3-CH3 or 4-CH3), 17.3 (d, 3JPC = 7.6 Hz,
3-CH3 or 4-CH3).
31P{1H} NMR (162 MHz, D2O): δ = 28.5 (s).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

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J. Dussart et al.
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Synthesis
[1-(4-Fluorophenyl)-1-hydroxyethyl]phosphinate Sodium Salt
(9b)
[1-(2-Chlorophenyl)-1-hydroxyethyl]phosphinate Sodium Salt
(9e)
White powder; yield: 1.85 g (82%).
White powder; yield: 2.1 g (85%).
IR (neat): 3240w (O–H), 2967w (C–HAr), 2913w (C–H), 2320w (P–H),
1682w (C=CAr), 1601w (C=CAr), 1163s (P=O), 1131w (C–F), 1043s (C–
OH), 1013w (P–O), 747w cm–1 (C–P).
IR (neat): 3160w (O–H), 2973w (C–HAr), 2901w (C–H), 2341w (P–H),
1581w (C=CAr), 1174s (P=O), 1096w (C–OH), 1036s (P–O), 753m (C–
Cl), 738w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 7.48–7.37 (m, 2 H, H3, H7), 7.10 (t, 3J =
8.9 Hz, 2 H, H4, H6), 6.63 (d, 1JPH = 516.1 Hz, PH), 1.61 (d, 3JPH = 14.3 Hz,
3 H, CH3).
1H NMR (400 MHz, D2O): δ = 7.54–7.48 (m, 1 H, H7), 7.31 (d, 3JHH = 7.7
Hz, 1 H, H4), 7.22 (t, 3JHH = 7.4 Hz, 1 H, H6), 7.01 (d, 1JPH = 533.4 Hz, PH),
2.54 (t, 3JHH = 7.4 Hz, 1 H, H5), 1.66 (d, 3JPH = 13.9 Hz, 3 H, CH3).
13C NMR (101 MHz, D2O): δ = 161.8 (dd, 1JFC = 243.1 Hz, 5JPC = 2.8 Hz,
C5), 137.1 (C2), 127.7 (dd, 3JFC = 8.3 Hz, 3JPC = 3.8 Hz, C3, C7), 114.8 (dd,
2JFC = 21.4 Hz, 4JPC = 2.0 Hz, C4, C6), 73.7 (d, 1JPC = 107.1 Hz, C1), 21.6 (d,
2JPC = 6.7 Hz, CH3).
13C NMR (101 MHz, D2O): δ = 139.3 (d, 2JPC = 3.3 Hz, C2), 131.5 (d, 3JPC
=
4.5 Hz, C3), 131.4 (d, 4JPC = 1.3 Hz, C4), 129.0 (d, 4JPC = 1.9 Hz, C6), 128.4
(d, 3JPC = 4.4 Hz, C7), 127.1 (C5), 75.2 (d, 1JPC = 103.6 Hz, C1), 22.0 (d, 2JPC
=
4.4 Hz, CH3).
19F{1H} NMR (377 MHz, D2O): δ = –116.6 (d, 6JFP = 3.9 Hz).
19F NMR (377 MHz, D2O): δ = –116.5 to –116.7 (m).
31P{1H} NMR (162 MHz, D2O): δ = 31.4 (d, 6JFP = 3.9 Hz).
31P NMR (162 MHz, D2O): δ = 31.4 (dq, 1JPH = 516.1 Hz, 3JPH = 14.2 Hz).
MS (ESI–): m/z = 203.03 [M – H]–, 429.04 [2 M – 2 H + Na]–.
31P{1H} NMR (162 MHz, D2O): δ = 27.9 (s).
31P NMR (162 MHz, D2O): δ = 27.9 (dq, 1JPH = 533.4 Hz, 3JPH = 13.9 Hz).
MS (ESI–): m/z = 219.00 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C8H9ClO3P: 218.9983; found:
218.9981.
HRMS (ESI–): m/z [M – H]– calcd for C8H9FO3P: 203.0279; found:
203.0277.
{1-Hydroxy-1-[4-(trifluoromethyl)phenyl]ethyl}phosphinate So-
dium Salt (9f)
White powder; yield: 2.51 g (91%).
[1-(4-Chlorophenyl)-1-hydroxyethyl]phosphinate Sodium Salt
(9c)
IR (neat): 3167w (O–H), 2987w (C–HAr), 2900w (C–H), 2316w (P–H),
1618w (C=CAr), 1412w (C–F), 1167s (P=O), 1073w (C–OH), 1025m (P–
O), 745w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 7.70 (d, 3JHH = 8.0 Hz, 2 H, H4, H6), 7.61 (d,
3JHH = 8.0 Hz, 2 H, H3, H7), 6.67 (d, 1JPH = 519.3, PH), 1.66 (d, 3JPH = 14.3
Hz, 1 H, CH3).
White powder; yield: 1.95 g (80%).
IR (neat): 3223br (O–H), 2988w (C–HAr), 2902w (C–H), 2339w (P–H),
1666w (C=CAr), 1580w (C=CAr), 1168m (P=O), 1093w (C–OH), 1024s
(P–O), 841w (C–Cl), 729w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 7.43–7.33 (m, 4 H, H3, H4, H6, H7), 6.62 (d,
13C NMR (101 MHz, D2O): δ = 145.8 (C2), 128.5 (dd, 2JFC = 32.2 Hz, 5JPC
=
1JPH = 516.4 Hz, PH), 1.60 (d, 3JPH = 14.3 Hz, 3 H, CH3).
3
2.5 Hz, C5), 126.3 (d, JPC = 3.6 Hz, C3, C7), 125.3–124.9 (m, C4, C6),
4
13C NMR (101 MHz, D2O): δ = 140.1 (C2), 132.5 (C5), 128.1 (d, JPC
=
124.3 (q, 1JFC = 271.2 Hz, C9), 74.1 (d, 1JPC = 105.1 Hz, C1), 21.7 (d, 2JPC
=
3
1
2.1 Hz, C4, C6), 127.5 (d, JPC = 3.8 Hz, C3, C7), 73.8 (d, JPC = 106.3 Hz,
5.7 Hz, C8).
C1), 21.6 (d, 2JPC = 6.3 Hz, C8).
19F{1H} NMR (377 MHz, D2O): δ = –62.3 (s)
19F NMR (377 MHz, D2O): δ = –62.3 (s).
31P{1H} NMR (162 MHz, D2O): δ = 30.8 (s).
31P NMR (162 MHz, D2O): δ = 30.8 (dq, 1JPH = 519.3 Hz, 3JPH = 14.3 Hz).
MS (ESI–): m/z = 253.02 [M – H]–.
31P{1H} NMR (162 MHz, D2O): δ = 31.1 (s).
31P NMR (162 MHz, D2O): δ = 31.1 (dq, 1JPH = 516.4 Hz, 3JPH = 14.3 Hz).
MS (ESI–): m/z = 219.00 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C8H9ClO3P: 218.9983; found:
218.9982.
HRMS (ESI–): m/z [M – H]– calcd for C9H9F3O3P: 253.0247; found:
253.0248.
[1-(3-Chlorophenyl)-1-hydroxyethyl]phosphinate Sodium Salt
(9d)
[1-Hydroxy-1-(4-methoxyphenyl)ethyl]phosphinate Sodium Salt
(9g)
White powder; yield: 1.82 g (75%).
IR (neat): 3163w (O–H), 2987w (C–HAr), 2926w (C–H), 2332w (P–H),
1620w (C=CAr), 1595w (C=CAr), 1568w (C=CAr), 1176s (P=O), 1045s (C–
OH), 1016w (P–O), 797 (C–Cl), 735 cm–1 (C–P) .
1H NMR (400 MHz, D2O): δ = 7.48 (s, 1 H, H3), 7.40–7.25 (m, 3 H, H5,
H6, H7), 6.64 (d, 1JPH = 517.9 Hz, PH), 1.62 (d, 3JPH = 14.4 Hz, 3 H, CH3).
13C NMR (101 MHz, D2O): δ = 143.9 (C2), 133.6 (d, JPC = 2.5 Hz, C4),
129.7 (d, JPC = 1.9 Hz, C5 or C6), 127.2 (d, JPC = 2.4 Hz, C5 or C6), 125.9 (d,
3JPC = 3.8 Hz, C3), 124.3 (d, 3JPC = 3.7 Hz,C7), 73.9 (d, 1JPC = 105.9 Hz, C1),
21.7 (d, 2JPC = 5.8 Hz, CH3).
31P{1H} NMR (162 MHz, D2O): δ = 30.9 (s).
31P NMR (162 MHz, D2O): δ = 30.9 (dq, 1JPH = 517.9 Hz, 3JPH = 14.4 Hz).
MS (ESI–): m/z = 219.00 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C8H9ClO3P: 218.9983; found:
218.9983.
White powder; yield: 1.45 g (61%).
IR (neat): 3199w (O–H), 2930w (C–HAr), 2835w (C–H), 2320w (P–H),
1610w (C=CAr), 1251m (C–O), 1175s (P=O), 1095w (C–OH), 1033s (P–
O), 750 cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 7.39 (dd, 3JHH = 8.8 Hz, 4JPH = 1.9 Hz, 2 H,
H3, H7), 6.98 (d, 3JHH = 8.8 Hz, 2 H, H4, H6), 6.62 (d, 1JPH = 513.6 Hz, PH),
3.80 (s, 3 H, OCH3), 1.60 (d, 3JPH = 14.2 Hz, 3 H, CH3).
4
13C NMR (101 MHz, D2O): δ = 157.9 (C5), 133.9 (C2), 127.3 (d, 3JPC = 3.9
4
1
Hz, C3, C7), 113.7 (d, JPC = 1.9 Hz, C4, C6), 73.6 (d, JPC = 107.8 Hz, C1),
55.3 (OCH3), 21.4 (d, 2JPC = 6.9 Hz, CH3).
31P{1H} NMR (162 MHz, D2O): δ = 31.7 (s).
31P NMR (162 MHz, D2O): δ = 31.7 (dq, 1JPH = 513.6 Hz, 3JPH = 14.3 Hz).
MS (ESI–): m/z = 215.05 [M – H]–.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

K
J. Dussart et al.
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Synthesis
HRMS (ESI–): m/z [M – H]– calcd for C9H12O4P: 215.0479; found:
215.0477.
(1-Hydroxy-1,2,3,4-tetrahydronaphthalen-1-yl)phosphinate Sodi-
um Salt (9k)
White powder; yield: 1.20 g (51%).
[1-Hydroxy-1-(m-tolyl)ethyl]phosphinate Sodium Salt (9h)
IR (neat): 3155w (O–H), 2995w (C–HAr), 2900w (C–H), 2312w (P–H),
1650w (C=CAr), 1172s (P=O), 1089w (C–OH), 1053s (P–O), 749m cm–1
(C–P) .
1H NMR (400 MHz, D2O): δ = 7.52–7.47 (m, 1 H, H3), 7.29–7.20 (m, 2
H, H4, H5), 7.20–7.14 (m, 1 H, H6), 6.76 (d, 1JPH = 514.1, PH), 2.83–2.63
(m, 2 H, H10), 2.28–2.16 (m, 1 H, H8a), 2.03–1.68 (m, 3 H, H8b, H9a, H9b).
White powder; yield: 2.01 g (91%).
IR (neat): 3207w (O–H), 2981w (C–HAr), 2905w (C–H), 2379w (P–H),
1668w (C=CAr), 1607w (C=CAr), 1150s (P=O), 1089w (C–OH), 1036m
(P–O), 747w cm–1 (C–P).
1H NMR (400 MHz, D2O): δ = 7.39–7.18 (m, 3 H, H3, H6, H7), 7.12 (d,
3JHH = 6.7 Hz 1 H, H5), 6.61 (d, 1JPH = 516.8 Hz, PH), 2.29 (s, 3 H, ArCH3),
1.59 (d, 3JPH = 14.3 Hz, 3 H, CH3).
13C NMR (101 MHz, D2O): δ =141.5 (C2), 138.3 (C4), 128.3 (d, 5JPC = 2.0
Hz, C5), 127.8 (d, 4JPC = 2.5 Hz, C6), 126.4 (d, 3JPC = 3.9 Hz, C3), 127.1 (d,
3JPC = 3.9 Hz, C7), 74.0 (d, 1JPC = 106.8 Hz, C1), 22.0 (d, 2JPC = 6.1 Hz, CH3),
20.6 (ArCH3).
2
13C NMR (101 MHz, D2O): δ = 138.6 (d, JPC = 5.1 Hz, C7), 135.9 (C2),
129.2 (C6), 127.6 (C5), 127.5 (d, 3JPC = 5.9 Hz, C3), 126.1 (C4), 71.7 (d, 1JPC
=
110.6 Hz, C1), 30.9 (d, 3JPC = 4.8 Hz, C8), 29.0 (C10), 18.5 (d, 2JPC = 4.7 Hz,
C9).
31P{1H} NMR (162 MHz, D2O): δ = 32.9 (s).
31P NMR (162 MHz, D2O): δ = 32.9 (dt, 1JPH = 514.1 Hz, 3JPH = 12.8 Hz).
MS (ESI–): m/z = 211.05 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C10H12O3P: 211.0530; found:
211.0528.
31P{1H} NMR (162 MHz, D2O): δ = 31.5 (s).
31P NMR (162 MHz, D2O): δ = 31.5 (dq, 1JPH = 516.8 Hz, 3JPH = 14.3 Hz).
MS (ESI–): m/z = 199.05 [M – H]–, 421.09 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C9H12O3P: 199.0530; found:
199.0529.
Funding Information
[1-Hydroxy-1-(o-tolyl)ethyl]phosphinate Sodium Salt (9i)
Université Paris 13, Sorbonne Paris Cité, Centre National de la Recher-
che Scientifique (CNRS), Ministère de l’Enseignement Supérieur et de
la Recherche (MESR), and GDR Phosphore (CNRS) are gratefully ac-
White powder; yield: 1.71 g (74%, purity >96%).
IR (neat): 3157w (O–H), 2988m (C–HAr), 2900m (C–H), 2313w (P-H),
1580w (C=CAr), 1174m (P=O), 1076m (C–OH), 1046s (P–O), 745w cm–1
(C–P).
knowledged for financial support.
)(
1H NMR (400 MHz, D2O): δ = 7.45–7.40 (1 H, H7), 7.25–7.17 (m, 3 H,
1
Supporting Information
H4, H5, H6), 6.82 (d, JPH = 518.1 Hz, PH), 2.54 (s, 3 H, ArCH3), 1.69 (d,
3JPH = 14.1 Hz, 3 H, CH3).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610274.
3
13C NMR (101 MHz, D2O): δ = 139.4 (C2), 137.2 (d, JPC = 4.5 Hz, C3),
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f
rmoaitn
132.5 (C4), 127.5 (d, 4JPC = 2.1 Hz, C7), 127.3 (d, 3JPC = 4.7 Hz, C5 or C6),
125.7 (d, 5JPC = 1.4 Hz, C5 or C6), 75.9 (d, 1JPC = 105.8 Hz, C1), 22.6 (d, 2JPC
5.3 Hz, CH3), 22.1 (ArCH3).
=
References
31P{1H} NMR (162 MHz, D2O): δ = 30.7 (s).
31P NMR (162 MHz, D2O): δ = 30.7 (dq, 1JPH = 518.1 Hz, 3JPH = 14.1 Hz).
MS (ESI–): m/z = 199.05 [M – H]–, 421.10 [2 M – 2 H + Na]–.
HRMS (ESI–): m/z [M – H]– calcd for C9H12O3P: 199.0530; found:
199.0530.
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(Hydroxydiphenylmethyl)phosphinate Sodium Salt (9j)
White powder; yield: 1.49 g (55%).
IR (neat): 3400w (O–H), 2988w (C–HAr), 2901w (C–H), 2338w (P–H),
1597w (C=CAr), 1170m (P=O), 1059s (C–OH), 1036w (P–O), 750w cm–1
(C–P).
1H NMR (400 MHz, D2O): δ = 7.43–7.36 (m, 4 H, H3, H7, H9, H13), 7.32–
7.19 (m, 6 H, H4, H5, H6, H10, H11, H12), 6.84 (d, 1JPH = 528.7 Hz, PH).
13C NMR (101 MHz, D2O): δ = 141.3 (d, 2JPC = 2.0 Hz, C2, C8), 128.3 (C4,
C6, C10, C12), 127.7 (d, 5J = 1.3 Hz, C5, C11), 127.3 (d, 3JHH = 4.9 Hz, C3, C7,
C9, C13), 78.8 (d, 1JPC = 105.4 Hz, C1).
31P{1H} NMR (162 MHz, D2O): δ = 30.5 (s).
31P NMR (162 MHz, D2O): δ = 30.5 (d, 1JPH = 528.7 Hz).
MS (ESI–): m/z = 247.05 [M – H]–.
HRMS (ESI–): m/z [M – H]– calcd for C13H12O3P: 247.0530; found:
247.0527.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–L

L
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