Synthesis of α-aminophosphinates by the hydrophosphinylation of imines

Article abstract of DOI:10.1002/hc.10133

Numerous substituted α-aminophosphinates were synthesized by addition of alkyl and phenyl H-phosphinates to aromatic imines and characterized. Modest diastereoselectivity was observed in the reaction. The size of the substituents exerts a small effect on the diastereoselectivity of P - C bond formation.

Full text of DOI:10.1002/hc.10133

Heteroatom Chemistry
Volume 14, Number 3, 2003
Synthesis of α-Aminophosphinates
by the Hydrophosphinylation of Imines
Andrea Szabo´,1 Imre Petneha´zy,1 and Zsuzsa M. Ja´szay2
1Department of Organic Chemical Technology, Budapest University of Technology and Economics,
H-1521, Budapest, P.O.B. 91, Hungary
2Organic Chemical Technology Research Group of the Hungarian Academy of Sciences,
H-1521, Budapest, P.O.B. 91, Hungary
Received 17 September 2002
pounds as there is no convenient and simple method
ABSTRACT: Numerous substituted ꢀ-aminophos-
for the synthesis of their phosphorus containing
phinates were synthesized by addition of alkyl and
precursors [5–9].
phenyl H-phosphinates to aromatic imines and char-
The most obvious way for their synthesis is the
acterized. Modest diastereoselectivity was observed in
Kabachnik–Field type reaction involving the addi-
the reaction. The size of the substituents exerts a small
tion of H-phosphinates to a C N double bond. The
effect on the diastereoselectivity of P C bond forma-
addition results in the products as the mixture of
ꢀ
C
tion.
2003 Wiley Periodicals, Inc. Heteroatom Chem
diastereomers because of the attack of the chiral
14:235–240, 2003; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.10133
H-phosphinate on the prochiral C-centre of C
bond (Scheme 1).
N
So far only a few attempts have been made for
the separation and determination of the pure di-
astereomers and enantiomers. Belov et al. [10] iso-
lated a single enantiomer of ethyl α-benzylamino-
phenylphosphinic acid by repeated recrystallization
from a diastereomeric mixture followed by resolu-
tion and determined the absolute configuration by
X-ray crystallography. A short report was also pub-
lished on the diastereoselectivity of the addition of
ethyl phenyl-H-phosphinate on several imines pre-
pared from isobutyraldehyde and different type of
benzyl and α-substituted benzylamines [11].
INTRODUCTION
In the past decades numerous synthetic meth-
ods have been developed for the synthesis of α-
aminophosphonic acids to study their biological ac-
tivity [1–3]. Because of their structural analogy with
α-amino carboxylic acids, they are considered to be
transition state analogues. Some of them are known
as herbicide (e.g. glyphosate), while others as en-
zyme inhibitor or neuroactive agent (e.g. NMDA re-
ceptor agonists) [4].
However, the α-aminophosphinic acids seem to
be closer analogues of α-amino carboxylic acids be-
cause of the higher stability of P C bond. Neverthe-
less, less publications are available on these com-
RESULTS AND DISCUSSION
We decided to study the reactions of a series of ethyl
alkyl-H-phosphinates 1 with imines 2 varying the
size of the substituent on the C N moiety to gen-
erate a high diastereoselectivity (Scheme 2).
The imines were prepared by the condensation
of the appropriate benzaldehyde with amines. The
Correspondence to: Imre Petneha´zy; e-mail: ipetnehazy@mail.
bme.hu.
Contract grant sponsor: National Science Foundation.
Contract grant number: OTKA T038108.
2003 Wiley Periodicals, Inc.
c
ꢀ
235

236 Szabo´, Petneha´zy, and Ja´szay
TABLE 1 α-Aminophosphinates Prepared and Ratio of
Diastereomers
n
R
Y
Ratio
δ
31P
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
Et
Et
Pr
Pr
Pr
i Pr
i Pr
Bu
Bu
Ph
Ph
Et
Et
Pr
i Pr
i Pr
Bu
Bu
H
4-Cl
H
4-Cl
2-Cl
H
4-Cl
H
4-Cl
H
2-Cl
H
4-Cl
4-Cl
H
4-Cl
H
4-Cl
60/40
56/44
51/49
58/42
64/36
58/42
46/54
52/48
54/46
55/45
40/60
52/48
52/48
53/47
45/55
43/57
49/51
53/47
54.7, 53.8
56.1, 53.9
55.4, 52.5
52.9, 52.4
52.3, 52.1
57.7, 52.3
55.8, 55.6
53.8, 52.9
53.2, 52.9
40.9, 38.7
40.3, 38.2
55.8, 55.2
55.2, 54.7
54.0, 53.3
57.1, 56.7
56.3, 55.6
54.9, 54.2
53.4, 53.0
SCHEME 1
α-aminophosphinates 3 were synthesized by the re-
action of the imine with the H-phosphinate at 50–
70◦C for 3 h. The conversion was almost quantitative
according to TLC. In most cases, the aminophosphi-
nate 3 was crystallized from the reaction mixture.
The results are summarized in Table 1.
The ratio of diastereomers was established by
means of 31P NMR measurements of the reaction
mixtures and confirmed after column chromatogra-
phy. The ratio of the diastereomers can also be deter-
mined from the 1H NMR spectra of ethyl ester groups
which gave rise to two distinct triplets.
The results demonstrate in all cases a slight
extent of diastereoselectivity, some tendencies can,
however, be observed. Comparing the effect on
the diastereoselectivity of substituted imines 2,
we found that the imines having ortho chloro-
substituent on the α-benzene ring gave better se-
lectivity than para- or unsubstituted ones, probably
due to the steric effects during the addition. As it
can be seen, the N-substituent of the imine (ben-
zyl or phenyl) exerts only a small effect on the
diastereoselectivity.
Finally, we report the results of diastereoselectiv-
ity observed in different solvents (Table 2). We chose
the model reaction of ethyl propyl-H-phosphinate
(1b) with imine 2c, and examined the ratio of di-
astereomers formed after 3 and 30 h. It can be seen
that both the conversion and diastereoselectivity is
low in ethanol, the diastereoselectivity values are
lower in acetonitrile and THF, than without solvent.
Interestingly, the value of the ratio of diastereomers
in toluene is inverted after 3 h compared to the exper-
iment performed without solvent namely from 60/40
to 40/60. After 30 h reaction time the diastereomeric
excess is destroyed in all experiments, possibly due
to the kinetic control.
TABLE 2 Ratio of Diastereomers and Conversion (%) in Dif-
ferent Solvents after 3 h and 30 h Reaction Time for 3d
Reaction Time (h)
3
30
Conversion
(%)
Conversion
(%)
Ratio
Ratio
Toluene
Acetonitrile
THF
Ethanol
No solvent
40/60
53/47
52/49
53/47
58/42
60
54
48
5
51/49
51/49
51/49
54/46
–
60
84
48
15
–
48
SCHEME 2

Synthesis of α-Aminophosphinates by the Hydrophosphinylation of Imines 237
94 Hz), CH3CH2P, 55.90 (d, JPC = 95.2 Hz), 56.51 (d,
EXPERIMENTAL
JPC = 95.1 Hz), CHP, 61.62 (d, JPC = 7.1 Hz), 61.83
(d, JPC = 7.1 Hz), CH3CH2O, 113.70, 113.81, 118.45,
118.52, 128.62, 128.74, 128.85, 129.10, 129.18,
129.25, 133.57, 134.08, 134.51, 145.74 ArC.
1H NMR and 13C NMR spectra were recorded on a
Bruker AC 250 instrument, while 31P NMR spectra
on a Bruker DRX-500 instrument, using TMS as the
internal standard (1H, 13C) and 85% H3PO4 as exter-
nal standard (31P), in CDCl3 solutions.
Ethyl (1-Phenylamino-phenylmethyl)-propylphos-
phinate (3c). mp 70◦C. Yield: 40%. 1H NMR δ: 1.01
(t, JHH = 7.1 Hz) CH3CH2CH2 major, 1.28 (t, JHH
=
General Procedure for ꢀ-Aminophosphinate 3
7.1 Hz) 3H, CH3CH2CH2 minor, 1.50–1.80 (m, 3H,
CH3CH2O), 1.68–1.80 (m, 2H, CH2CH2P), 1.80–1.95
A mixture of the imine 2 (10 mmol) and ethyl
alkylphosphinate 1 (30 mmol) was stirred at 50–
70◦C for 3 h. After cooling to room temperature the
aminophosphinates 3a–h were crystallised from the
reaction mixture, then the product was recrystallised
from hexane–ethyl acetate 8:2. Compounds 3i–r
were isolated by column chromatography (toluene–
acetone 17:3) on silica gel. Products 3i–k and 3n–p
were isolated as viscous oils whereas 3l, m, q, and r
as white solids.
(m, JPH = 13.0 Hz, 2H, PCH2CH2), 3.26 (dq, JHH
=
7.2 Hz, JPH = 10.1 Hz), 3.74 (dq, JHH = 7.2 Hz, JPH
= 10.1 Hz), 2H, OCH2, 4.58 (dd, JHH = 7.5 Hz, JPH
=
15.6 Hz, 1H, PCH), 4.95 (b, 1H, NH), 6.58–6.72 (m,
3H, ArH), 7.09–7.52 (m, 7H, ArH). 13C NMR δ: 15.63
(d, JPC = 5.1 Hz, CH3CH2O), 15.82 (d, JPC = 13.4 Hz,
CH3CH2CH2), 16.58 (d, JPC = 5.2 Hz, CH3CH2CH2),
29.91 (d, JPC = 92.0 Hz, CH2CH2P), 57.38 (d, JPC
=
94.2 Hz, CHP), 61.7 (d, JPC = 6.9 Hz, CH2CH2O),
114.04, 118.54, 128.05, 128.11, 128.18, 128.77,
128.80, 129.37, 138.25, 138.30, 145.58, 146.01, ArC.
Ethyl (1-Phenylamino-phenylmethyl)-ethylphos-
phinate (3a). mp 75◦C. Yield: 47%. 1H NMR δ: 1.01
(dt, JHH = 7.7 Hz, JPH = 18 Hz), 1.19, (dt, JHH = 7.7 Hz,
JPH = 18 Hz) 3H, PCH2CH3, 1.02 (t, JHH = 7.0 Hz),
1.28 (t, JHH = 7.0 Hz) 3H, OCH2CH3, 1.54 Hz (dq,
JHH = 7.7 Hz, JPH = 13 Hz), 1.88 (dq, JHH = 7.7 Hz,
JPH = 13 Hz) 2H, PCH2, 3.26 (dq, JHH = 7.0 Hz,
JPH = 10.0 Hz), 3.75 (dq, JHH = 7.0 Hz, JPH = 10.0 Hz),
3.97–4.21 (m), 2H, OCH2, 4.11 (d, JPH = 17.3 Hz, 1H,
PCH), 4.57–4.71 (m, 1H, NH), 6.58–6.71 (m, ArH,
3H), 7.07–7.45 (m, 7H, ArH). 13C NMR δ: 5.57 (d, JPC
= 34 Hz), 5.67 (d, JPC = 34 Hz), CH3CH2P, 16.42 (d,
JPC = 5 Hz), 16.71 (d, JPC = 5 Hz), CH3CH2O, 19.16
(d, JPC = 94 Hz), 20.68 (d, JPC = 94 Hz), CH3CH2P,
56.65 (d, JPC = 91 Hz), 57.27 (d, JPC = 91 Hz) CHP.
61.53 (d, JPC = 7.0 Hz), 61.87 (d, JPC = 7.0 Hz),
CH3CH2O, 113.85, 113.97, 118.37, 127.54, 127.62,
127.90, 127.95, 128.01, 128.63, 128.81, 129.19,
136.13, 146.20, 146.36 ArC.
Ethyl (1-Benzylamino-(4-chloro)-phenylmethyl)-
propylphosphinate (3d). mp 85◦C. Yield: 48%. 1H
NMR δ: 1.04 (t, JHH = 7.0 Hz, 3H, CH3CH2O), 1.25–
1.37 (m, JHH = 7.0 Hz, 3H, CH3CH2CH2), 1.36–1.69
(m, 2H, CH2CH2P), 1.69–1.92 (m, JPH = 12.2 Hz, 2H,
PCH2CH2), 3.37 (dq, JHH = 7.0 Hz, JPH = 10.0 Hz),
3.81 (dq, JHH = 7.0 Hz, JPH = 10.0 Hz), 4.02–4.13
(m, JHH = 7.0 Hz) 2H, OCH2, 4.09 (d, JPH = 18.3 Hz,
1H, PCH), 4.54–4.68 (m, 1H, NH), 6.56–6.74 (m,
2H, ArH), 7.26–7.40 (m, 7H, ArH). 13C NMR δ:
15.38 (d, JPC = 5.4 Hz, CH3CH2O), 15.44 (d, JPC
= 13.4 Hz, CH3CH2CH2), 16.42 (d, JPC = 5.0 Hz,
CH3CH2CH2), 29.48 (d, JPC = 92 Hz, CH2CH2P), 56.54
(d, JPC = 94.5 Hz, CHP), 61.7 (d, JPC = 6.9 Hz,
CH2CH2O), 113.80, 113.91, 118.57, 128.76, 128.94,
129.20, 129.31, 133.67, 134.19, 146.00, ArC.
Ethyl (1-Benzylamino-(2-chloro)-phenylmethyl)-
1
Ethyl (1-Phenylamino-(4-chloro)-phenylmethyl)-
ethylphosphinate (3b). mp 78◦C. Yield: 59%. 1H
NMR δ: 1.03 ppm (dt, JHH = 7.6 Hz, JPH = 18 Hz),
1.15 (dt, JHH = 7.6 Hz, JPH = 18 Hz) 3H, PCH2CH3,
1.08 (t, JHH = 6.8 Hz), 1.28 (t, JHH = 6.8 Hz), 3H,
OCH2CH3, 1.60 (dq, JHH = 7.6 Hz, JPH = 15 Hz), 1.90
(dq, JHH = 7.6 Hz, JPH = 15 Hz) 2H, PCH2, 3.41 (dq,
JPH = 10.0 Hz), 3.82 (dq, JHH = 10.0 Hz), 4.00–4.23
(m), 2H, OCH2, 4.10 (d, JPH = 17.0 Hz, 1H, PCH),
4.57–4.71 (m, JHH = 17.0 Hz, 1H, NH), 6.57–6.73 (m,
2H, ArH), 7.08–7.41 (m, 7H, ArH). 13C NMR δ: 5.46
(d, JPC = 33.0 Hz), 5.48 (d, JPC = 33.0 Hz), CH3CH2P,
16.33 (d, JPC = 5.3 Hz), 16.56 (d, JPC = 5.3 Hz),
propylphosphinate (3e). mp 125◦C. Yield: 18%. H
NMR δ: 0.88 (t, JHH = 6.9 Hz), 1.30 (t, JHH
6.9 Hz) 3H, CH3CH2O, 0.99 (dt, JHH = 7.3 Hz, JPH
17.9 Hz, 3H, CH3CH2CH2), 1.40–1.70 (m, 2H, JPH
=
=
=
12.2 Hz, CH2CH2P), 1.88–1.97 (m, JPH = 14.2 Hz, 2H,
PCH2CH2), 3.15 (dq, JHH = 6.9 Hz), 3.67 (dq, JHH
=
6.9 Hz), 4.10–4.27 (m, JHH = 6.9 Hz) 2H, OCH2, 4.17
(dd, JHH = 7.3 Hz, JPH = 17.4 Hz, 1H, PCH), 5.22–5.29
(m, 1H, NH), 6.56–6.70 (m, 2H, ArH), 7.07–7.55 (m,
7H, ArH).
Ethyl (1-Phenylamino-phenylmethyl)-isopropyl-
phosphinate (3f). mp 85◦C. Yield: 75%. 1H NMR
δ: 0.95 (t, JHH = 7.0 Hz), 1.24 (t, JHH = 7.0 Hz)
CH3CH2O, 19.43 (d, JPC = 96 Hz), 20.37 (d, JPC
=

238 Szabo´, Petneha´zy, and Ja´szay
3H, CH3CH2O, 1.08 (dd, JHH = 7.0 Hz, JPH = 17.2),
Ethyl (1-Phenylamino-phenylmethyl)-butylphos-
phinate (3i). oil. Yield: 82%. 1H NMR δ: 0.75 (t, JHH
= 7.2 Hz), 0.81 (t, JHH = 7.2 Hz) 3H, CH3CH2, 0.96 (t,
JHH = 7.0 Hz), 1.18 (t, JHH = 7.0 Hz) 3H, CH3CH2O,
1.20–1.39 (m, JHH = 7.2 Hz, 2H, CH3CH2), 1.39–1.69
(m, JHH = 7.0 Hz, 2H, CH3CH2CH2), 1.63–1.93 (m, JPH
= 13.0 Hz, 2H, CH2P), 3.23–3.38 (m, JHH = 7.0 Hz),
1.09 (dd, JHH = 7.0 Hz, JPH = 17.2 Hz), 1.23 (JHH
7.0 Hz, JPH = 16.9 Hz), 1.24 (dd, JHH = 7.0 Hz, JPH
=
=
16.9 Hz), 6H, CH3CH, 1.70–1.89 (m, JPH = 13.0 Hz)
2.08–2.28 (m, JPH = 13.0 Hz) 1H, CH3CH, 3.13 (dq,
JHH = 7.5 Hz, JPH = 10.0 Hz) 3.68 (dq, JHH = 7.5 Hz,
JPH = 10 Hz) 3.92–4.14 (m, JHH = 7.5 Hz) 2H, OCH2,
4.05 (dd, JHH = 7.3 Hz, JPH = 17.6 Hz, 1H, PCH),
4.67–4.79 (m, 1H, NH), 6.57–6.63 (m, 3H, ArH),
7.06–7.12 (m, 2H, ArH), 7.25–7.47 (m, 5H, ArH).
3.60–3.81 (m, JHH = 7.0 Hz), 3.87–4.15 (m, JHH
=
7.0 Hz), 2H, OCH2, 4.00 (d, JPH = 17.6 Hz, 1H, PCH),
4.48–4.62 (m, 1H, NH), 6.49–6.63 (m, 3H, ArH), 6.98–
7.04 (m, 2H, ArH), 7.19–8.04 (m, 4H, ArH).
13C NMR δ: 15.11 (d, JPC = 4.7 Hz), 15.34 (d, JPC
=
4.7 Hz), CH3CH2O, 16.53 (d, JPC = 22.6 Hz), 16.61
(d, JPC = 22.6 Hz) CH3CH, 25.42 (d, JPC = 107.0 Hz),
Ethyl (1-Phenylamino-phenylmethyl)-phenylpho-
1
26.91 (d, JPC = 107 Hz), CH3CHP, 54.58 (d, JPC
=
sphinate (3j). mp <25◦C. Yield: 57%. H NMR δ:
93.0 Hz), 55.73 (JPC = 93.0 Hz), CHP, 61.63 (d, JPC
= 7.3 Hz), 62.13 (d, JPC = 7.3 Hz), OCH2, 113.54,
113.75, 117.98, 118.20, 127.59, 127.93, 128.32,
128.50, 128.98, 135.73, 145.80, 145.95, ArC.
1.13 (t, JHH = 7.0 Hz), 1.34 (t, JHH = 7.0 Hz) 3H,
OCH2CH3, 3.74 (dq, JHH = 7.0 Hz, JPH = 14.0 Hz),
3.87 (dq, JHH = 7.0 Hz, JPH = 14.0 Hz), 4.04–4.25 (m,
JHH = 7.0 Hz), 2H, OCH2, 4.11 (d, JPH = 19.1 Hz),
4.14 (d, JPH = 19.1 Hz), 1H, PCH, 4.83 (b, 1H, NH),
6.50–6.70 (m, 2H), 7.00–7.14 (m, 4H), 7.25–8.54 (m,
8H), 7.75–7.82 (m, 1H) ArH. 13C NMR δ: 16.35 (d, JPC
= 5.9 Hz), 16.60 (d, JPC = 5.9 Hz) CH3CH2O, 58.45
(d, JPC = 105.0 Hz), 59.0 (d, JPC = 105.0 Hz) CHP,
61.9 (d, JPC = 6.8), 62.15 (d, JPC = 6.8) CH2CH2O,
113.9, 118.3, 127.3, 127.6, 127.8, 128.2, 128.2, 128.3,
128.4, 128.5, 128.6, 129.1, 131.9, 132.2, 132.5, 132.6,
Ethyl (1-Benzylamino-(4-chloro)-phenylmethyl)-
isopropylphosphinate (3g). mp 120◦C. Yield: 56%.
1H NMR δ: 1.01 (t, JHH = 6.9 Hz), 1.25 (t, JHH
=
6.9 Hz) 3H, CH3CH2O, 1.11 (dd, JHH = 7.0 Hz, JPH
= 16.9 Hz), 1.13 (dd, JHH = 7.0 Hz, JPH = 16.9 Hz),
1.23 (dd, JHH = 7.0 Hz, JPH = 17.0 Hz), 1.25 (dd, JHH
= 7.0 Hz, JPH = 17.0 Hz) 6H, CH3CH, 1.87 (heptett,d,
JHH = 7.1 Hz, JPH = 12.0 Hz), 2.18 (heptett,d, JHH
7.1 Hz, JPH = 12.0 Hz) 1H, CH3CH, 3.24 (dq, JHH
7.1 Hz, JPH = 10 Hz), 3.76 (dq, JHH = 7.1 Hz, JPH
=
=
=
ArC, 134.1 (d, JPC = 190.0 Hz, PCAr), 146.4 (d, JPC =
16.7 Hz), 146.6 (d, JPC = 13 Hz) NHCAr. IR (neat):
3403, 1211, 1038, 956 cm−1.
10.0 Hz), 3.90–4.20 (m, JHH = 7.3 Hz), 2H, OCH2, 4.03
(dd, JHH = 7.3 Hz, JPH = 17.0 Hz 1H, PCH), 4.66–4.78
(m, 1H, NH), 6.55–6.72 (m, 2H, ArH), 7.07–7.15 (m,
2H, ArH), 7.26–7.42 (m, 5H, ArH). IR (KBr): 3273,
1205, 1029, 961 cm−1.
Ethyl (1-Phenylamino-(2-chloro)-phenylmethyl)-
1
phenylphosphinate (3k). mp <25◦C. Yield: 64%. H
NMR δ 1.06 (t, JHH = 7.1 Hz), 1.38 (t, JHH = 7.1 Hz)
3H, OCH2CH3, 3.64 (dq, JHH = 7.0 Hz, JPH = 17 Hz),
3.78 (dq, JHH = 7.0 Hz, JPH = 17 Hz), 4.14–4.33 (m, JHH
= 7.0 Hz), 2H, OCH2, 5.12 (b), 5.23 (b) 1H, NH, 5.41
(d, JPH = 17.4 Hz), 5.44 (d, JPH = 17.4 Hz), 1H, PCH,
6.48–6.63 (m, 1H), 7.00–7.56 (m, 11H), 7.82–8.02 (m,
2H) ArH. 13C NMR δ: 16.33 (d, JPC = 6.3 Hz), 16.76
(d, JPC = 6.3 Hz) CH3CH2O, 53.93 (d, JPC = 106.7 Hz)
54.17 (d, JPC = 102.5 Hz) CHP, 62.0 (d, JPC = 7.0),
62.52 (d, JPC = 7.0) CH2CH2O, 113.7, 118.5, 127.5,
128.0, 128.2, 128.7, 128.9, 129.1, 129.3, 129.4, 131.8,
Ethyl (1-Phenylamino-phenylmethyl)-butylphos-
phinate (3h). mp 68◦C. Yield: 94%. 1H NMR δ: 0.81
(t, JHH = 7.2 Hz), 0.9 (t, JHH = 7.2 Hz) 3H, CH3CH2,
1.01 (t, JHH = 7.0 Hz), 1.28 (t, JHH = 7.0 Hz) 3H,
CH3CH2O, 1.34–1.47 (m, JHH = 7.3 Hz, 2H, CH3CH2),
1.47–1.64 (m, JHH = 7.0 Hz, 2H, CH2CH2), 1.75–1.98
(m, JPH = 13.1 Hz, 2H, CH2P), 3.24 (dq, JHH = 7.1 Hz,
JPH = 10.0 Hz), 3.75 (dq, JHH = 7.1 Hz, JPH = 10.0 Hz),
3.95–4.21 (m, JHH = 7.1 Hz) 2H, OCH2, 4.1 (d, JPH
=
132.0, 132.3, 132.5, 132.7, 132.8, ArC, 113.7 (d, JPC
128.1 Hz, PCAr), 145.9 (d, JPC = 16.7 Hz, NHCAr).
=
18.0 Hz, 1H, PCH), 4.54–4.72 (m, 1H, NH), 6.58–6.71
(m, 3H, ArH), 7.07–7.44 (m, 7H, ArH). 13C NMR: δ:
13.56 (d, JPC = 7.0 Hz, CH3CH2CH2), 16.42 (d, JPC
=
Ethyl (1-Benzylamino-phenylmethyl)-ethylphos-
1
5.4 Hz), 16.62 (JPC = 5.4 Hz), CH3CH2O, 23.23 (d, JPC
= 4.7 Hz), 23.97 (d, JPC = 4.7 Hz) CH3CH2CH2, 23.72
(CH3CH2CH2), 26.16 (d, JPC = 94.9 Hz), 27.33 (d, JPC
= 94.8 Hz) CH2CH2P, 57.37 (d, JPC = 94.5 Hz), 57.58
(d, JPC = 94.5 Hz) CHP, 61.50 (d, JPC = 7.1 Hz), 61.83
(d, JPC = 7.1 Hz) CH2CH2O, 113.80, 114.0, 118.31,
127.56, 127.63, 127.87, 128.06, 128.58, 128.78,
129.17, 135.73, 135.79, 136.18, 146.26, 146.46, ArC.
phinate (3l). mp 52◦C. Yield: 53%. H NMR δ: 0.98
(t, JHH = 7.6 Hz, JPH = 17.6 Hz), 1.06 (t, JHH
=
7.6 Hz, JPH = 17.6 Hz) 3H, PCH2CH3, 1.03 (t, JHH
= 7.2 Hz), 1.28 (t, JHH = 7.2 Hz) 3H, OCH2CH3, 1.42–
1.64 (m, JPH = 13.9 Hz), 1.78 (dq, JHH = 7.6 Hz, JPH
= 13.9 Hz) 2H, PCH2, 2.77 (s, 1H, NH), 3.44–3.57
(m, JHH = 7.2), 3.78–4.20 (m, JHH = 7.2 Hz), 2H,
OCH2, 3.46 (d, JAB = 9.6 Hz), 3.54 (d, JAB = 9.6 Hz),

Synthesis of α-Aminophosphinates by the Hydrophosphinylation of Imines 239
1H. CH2ANH, 3.81 (d, JAB = 9.6 Hz), 3.86 (d, JAB
=
JHH = 12.7 Hz, 1H, CH2B-Ar), 3.92 (d, JPH = 14.5 Hz,
1H, PCH), 7.17–7.40 (m, 10H, ArH).
9.6 Hz), 1H, CH2BNH, 3.81 (d, JPH = 17.0 Hz, 1H,
PCH), 7.21–7.27 (m, 4H, ArH), 7.29–7.40 (m, 6H,
ArH). 13C NMR δ: 5.37 (CH3CH2P), 16.10 (d, JPC
=
Ethyl (1-Benzylamino-(4-chloro)-phenylmethyl)-
isopropylphosphinate (3p). mp <25◦C. Yield: 68%.
1H NMR δ: 0.80–0.99 (m, JHH = 6.9 Hz, 6H, CH3CH),
1.03 (t, JHH = 7.1 Hz), 1.15 (t, JHH = 7.1 Hz),
2H, CH3CH2O, 1.69 (heptett,d, JHH = 7.1 Hz, JPH
5.3 Hz), 16.59 (d, JPC = 5.3 Hz) CH3CH2O, 18.50 (d,
JPC = 94 Hz), 19.10 (d, JPC = 94 Hz) CH3CH2P, 50.77
(d, JPC = 15.6 Hz), 51.02 (d, JPC = 5.3 Hz) CH2NH,
60.06 (d, JPC = 94.0 Hz), 60.17 (d, JPC = 94.0 Hz)
CHP, 61.28 (d, JPC = 7.0 Hz), 61.82 (d, JPC = 7.0 Hz)
CH3CH2O, 126.90, 127.67, 128.06, 128.13, 128.37,
128.53, 135.44, 135.51, 135.72, 139.15, ArC.
= 11.6 Hz), 2.06 (heptett,d, JHH = 7.1 Hz, JPH
=
11.6 Hz), 1H, CH3CH3CH, 2.21 (b, 1H, NH), 3.27–
3.41 (m, JHH = 7.1 Hz), 3.60–4.08 (m, JHH = 7.1 Hz)
2H, CH3CH2O, 3.30 (d, JAB = 13.4 Hz), 3.35 (d, JAB
= 13.4 Hz), 1H, CH2ANH, 3.66 (d, JAB = 13.0 Hz),
3.82 (d, JAB = 13.2), 1H, CH2BNH, 3.88 (d, JPH
= 19.6 Hz, 1H, CH), 6.91–7.28 (m, 9H, ArH). 13C
NMR δ: 14.57 (d, JPC = 4.7 Hz), 14.65 (d, JPC
= 4.7 Hz) CH3CH3CH, 15.52 (d, JPC = 4.9 Hz),
Ethyl (1-Benzylamino-(4-chloro)-phenylmethyl)-
ethylphosphinate (3m). mp 58◦C. Yield: 92%. 1H
NMR δ: 0.90 (dt, JHH = 7.7 Hz, JPH = 13.6 Hz, 3H,
PCH2CH3), 0.98 (t, JHH = 7.1 Hz), 1.19 (t, JHH
=
7.1 Hz) 3H, OCH2CH3, 1.26–1.56 (m, JPH = 15.4 Hz),
1.59–1.75 (m, JPH = 15.4 Hz) 2H, PCH2, 2.34 (b, 1H,
NH), 3.35 (d, JAB = 12.7 Hz), 3.40 (d, JAB = 12.7 Hz)
1H, CH2ANH, 3.69 (d, JAB = 12.7 Hz), 3.70 (d, JAB
= 12.7 Hz), 1H, CH2BNH, 3.46–3.59 (m, JHH = 7.1),
16.35 (d, JPC = 4.9 Hz) CH3CH2O, 24.76 (d, JPC
=
93.4 Hz), 25.55 (d, JPC = 82.0 Hz) CH3CHP, 50.37
(d, JPC = 17 Hz), 50.65 (d, JPC = 18.3 Hz) CH2NH,
57.50 (d, JPC = 96.3 Hz), 59.00 (d, JPC = 93.0 Hz),
CHP, 62.35 (d, JPC = 6.9 Hz), 62.54 (JPC = 6.9 Hz)
CH3CH2O, 127.73, 127.81, 127.87, 128.18, 128.52,
129.53, 129.62, 133.93, 134.20, 138.55, 138.61, ArC.
3.66–4.01 (m, JHH = 7.1 Hz), 2H, OCH2, 3.85 (d, JPH
=
17 Hz, 1H, PCH), 7.20–7.40 (m, 9H, ArH). 13C NMR
δ: 4.99 (d, JPC = 15.3 Hz) 5.08 (d, JPC = 15.4 Hz),
CH3CH2P, 16.09 (d, JPC = 5.2 Hz), 16.33 (d, JPC
=
5.2 Hz), CH3CH2O, 18.23 (d, JPC = 94.0 Hz), 18.76
(d, JPC = 94.0 Hz) CH3CH2P, 50.49 (d, JPC = 15.4 Hz),
Ethyl (1-Benzylamino-phenylmethyl)-butylphos-
1
phinate (3q). mp 56◦C. Yield: 74%. H NMR δ: 0.8
50.75 (d, JPC = 15.4 Hz) CH2NH, 59.23 (d, JPC
=
(t, JHH = 7.1 Hz), 0.87 (t, JHH = 7.1 Hz) 3H, CH3CH2,
1.03 (t, JHH = 7.0 Hz), 1.28 (t, JHH = 7.0 Hz) 3H,
CH3CH2O, 1.30–1.46 (m, JHH = 7.4 Hz, 2H, CH3CH2),
1.46–1.61 (m, 2H, CH3CH2CH2), 1.70–1.76 (m, JPH
= 13.0 Hz, 2H, CH2P), 2.53 (b, 1H, NH), 3.42–3.55
(m, JHH = 7.1 Hz), 3.70–4.12 (m, JHH = 7.1 Hz) 2H,
OCH2, 3.46 (d, JAB = 13.0 Hz), 3.50 (d, JAB = 13.0 Hz)
99.0 Hz), 60.14 (d, JPC = 97.0 Hz), CHP, 60.75 (d, JPC
= 7.0 Hz), 61.17 (d, JPC = 7.0 Hz) CH3CH2O, 126.81,
127.93, 127.99, 128.33, 128.47, 129.20, 129.28,
129.61, 129.69, 133.21, 133.91, 133.97, 134.21,
ArC.
Ethyl (1-Benzylamino-(4-chloro)-phenylmethyl)-
1H, CH2ANH, 3.80 (d, JAB = 13.0 Hz), 3.82 (d, JAB =
1
propylphosphinate (3n). mp <25◦C. Yield: 61%. H
13.0 Hz) 1H, CH2BNH, 3.95 (d, JPH = 17.0 Hz, 1H,
PCH), 7.25–7.38 (m, 10H, ArH).
NMR δ: 0.92 (t, JHH = 6.9 Hz), 0.95 (t, JHH = 6.9 Hz)
3H, CH3CH2CH2, 1.07 (t, JHH = 7.2 Hz), 1.26 (t, JHH
=
7.2 Hz), 3H, CH3CH2O, 1.41–1.58 (m, JHH = 7.5 Hz,
2H, CH2CH2P), 1.63 (b, 1H, NH), 1.67–1.84 (m, JPH
= 12.7 Hz, 2H, PCH2CH2), 3.49 (d, JAB = 13.2 Hz),
Ethyl (1-Benzylamino-(4-chloro)-phenylmethyl)-
butylphosphinate (3r). mp 61◦C. Yield: 88%. 1H
NMR δ: 0.83 (t, JHH = 6.9 Hz), 0.88 (t, JHH = 6.9 Hz)
3.57 (d, JAB = 13.2 Hz) 1H, CH2ANH, 3.81 (d, JAB
=
3H, CH3CH2, 1.07 (t, JHH = 7.2 Hz), 1.28 (t, JHH =
13.2 Hz), 3.95 (d, JAB = 13.2 Hz), 1H, CH2BNH, 3.51–
3.66 (m, JHH = 7.1 Hz), 3.79–4.15 (m, JHH = 7.1 Hz),
2H, OCH2, 3.91 (d, JPH = 16.0 Hz, 1H, PCH), 7.10–
7.30 (m, 7H, ArH), 7.34–7.36 (m, 2H, ArH).
7.2 Hz) 3H, CH3CH2O, 1.33–1.45 (m, JHH = 7.2 Hz,
2H, CH3CH2), 1.45–1.65 (m, JHH = 7.2 Hz, 2H,
CH3CH2CH2), 1.76 (dt, JHH = 7.2 Hz, JPH = 13.6 Hz,
2H, CH2P), 2.43 (b, 1H, NH), 3.44 (d, JAB = 12.6 Hz),
3.49 (d, JAB = 12.6 Hz), 1H, CH2ANH, 3.79 (d, JAB
=
Ethyl (1-Benzylamino-phenylmethyl)-isopropyl-
phosphinate (3o). oil. Yield: 53%. 1H NMR δ:
0.83–1.12 (m, JHH = 7.0 Hz, 6H, CH3CH), 1.03 (t,
JHH = 7.0 Hz), 1.19 (t, JHH = 7.0 Hz), 3H, CH3CH2O,
12.6 Hz), 3.81 (d, JAB = 12.6 Hz), 1H, CH2BNH, 3.50–
3.67 (m, JHH = 7.2 Hz), 3.77–4.16 (m, JHH = 7.2 Hz)
2H, OCH2, 3.93 (d, JPH = 17.0 Hz, 1H, PCH), 7.25–
7.35 (m, 9H, ArH). 13C NMR δ: 13.56 (d, JPC = 3.5 Hz,
1.61–1.83 (m, JHH = 7.0 Hz,), 2.03–2.23 (m, JHH
=
CH3CH2CH2), 16.49 (d, JPC = 5.5 Hz), 16.73 (JPC =
7.0 Hz), 1H, CH3CH, 2.44 (b, 1H, NH), 3.23–3.56
(m, JHH = 7.1 Hz), 3.61–4.17 (m, JHH = 7.1 Hz) 2H,
OCH2, 3.45 (d, JAB = 12.0 Hz, 1H, CH2A-Ar), 3.72 (d,
5.5 Hz) CH3CH2O, 23.21 (d, JPC = 4.8 Hz), 23.49
(JPC = 5.1 Hz) CH3CH2CH2, 23.89 (d, JPC = 15.9 Hz,
CH3CH2CH2), 25.20 (d, JPC = 92.6 Hz), 25.80 (d, JPC
=

240 Szabo´, Petneha´zy, and Ja´szay
Kuhkar, V. P.; Hudson, H. R. (Eds.); Wiley: Chichester,
UK, 2000, pp. 537–558.
[2] Kafarski, P.; Lejczak, B. Phosphorus Sulfur Silicon
1991, 63, 193.
[3] Redmore, D. In Topics in Phosphorus Chemistry;
Grayson, M.; Griffith, E. J. (Eds.); InterScience: New
York, 1976; Vol. VIII, pp. 515–585.
[4] Hewling, P. L.; Emre, M.; Watkins, Y. C. In Excita-
tory Aminoacids-Clinical Results with Antagonists;
Herrling, G. P. L. (Ed.); Academic Press: London,
1997; p. 7.
92.6 Hz) CH2CH2P, 50.91 (d, JPC = 19.2 Hz), 51.18 (d,
JPC = 19.2 Hz) NHCH2, 60.00 (d, JPC = 98.4 Hz), 60.80
(d, JPC = 96.0 Hz) CHP, 61.08 (d, JPC = 6.9 Hz), 61.42
(d, JPC = 6.9 Hz) CH2CH2O, 127.20, 127.23, 128.38,
128.41, 128.76, 128.84, 128.87, 129.55, 129.63,
130.05, 133.55, 133.60, 134.47, 134.54, 139.09, ArC.
ACKNOWLEDGMENT
A. Szabo´ is grateful to Richter Gedeon Rt. for a
scholarship.
[5] Maier, L. Phosphorus Sulfur Silicon 1983, 14, 295.
[6] Baylis, E. K.; Campbell, C. D.; Dingwall, J. G. J Chem
Soc, Perkin Trans I 1984, 2845.
[7] Gajda, T. Phosphorus Sulfur Silicon 1993, 85, 59.
[8] Dingwall, J. G.; Ehrenfreud, J.; Hall, R. G. Tetrahe-
dron 1989, 45, 3787.
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