Alkylamides of trivalent phosphorus-acids: Phosphorus-nitrogen diad tautomerism

Article abstract of DOI:10.1016/S0040-4039(00)01388-5

Alkylamides of trivalent phosphorus acids I exist in prototropic equilibrium with PH-iminophosphoranes 2. Phosphorus-nitrogen diad tautomeric equilibrium 1 ? 2 depends on the nature of solvents and the substituents at the phosphorus and nitrogen atoms shi

Full text of DOI:10.1016/S0040-4039(00)01388-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 7997–8000
Alkylamides of trivalent phosphorus-acids:
phosphorus–nitrogen diad tautomerism
Oleg I. Kolodiazhnyi* and Natalia Prynada
Department of Physiologically Active Compound Synthesis, Institute of Bioorganic Chemistry,
National Academy of Sciences of the Ukraine, Murmanskaya Str., 1, Kiev-94, 02094, Ukraine
Received 28 June 2000; revised 7 August 2000; accepted 16 August 2000
Abstract
Alkylamides of trivalent phosphorus acids 1 exist in prototropic equilibrium with PH–iminophosphor-
anes 2. Phosphorus–nitrogen diad tautomeric equilibrium 1 X 2 depends on the nature of solvents and the
substituents at the phosphorus and nitrogen atoms shifting towards the tautomeric form possessing the
least mobile proton. © 2000 Published by Elsevier Science Ltd.
Keywords: phosphorus–nitrogen diad prototropic tautomerism; tris(alkylamino)phosphines; bis-alkylamides of phos-
phonic acids; tris[(S)-a-methylbenzylamino]phosphine.
We have recently described chiral symmetric esters of phosphoric acid prepared from optically
active natural alcohols (glucofuranose, borneol, menthol, etc.) and demonstrated that these
1–3
esters are suitable starting materials for asymmetric synthesis.
Proceeding with these studies, we have prepared the chiral symmetric alkylamides of trivalent
phosphorus acids 1, R%=(S)-CH(Me)C H possessing interesting chemical properties (Scheme
6
5
Scheme 1.
*
Corresponding author. Fax: 38(044)573-2552; e-mail: oik@bpci.kiev.ua
0
040-4039/00/$ - see front matter © 2000 Published by Elsevier Science Ltd.
PII: S0040-4039(00)01388-5

7998
1
). Thus, we found that the compounds 1 exist in tautomeric equilibrium with PH–iminophos-
phoranes 2. Formerly the phosphorus–nitrogen diad prototropy of trivalent phosphorus com-
pounds 1 containing alkylamino groups was not described, although PH–iminophosphoranes,
R P(H)ꢀNR%, containing electron-accepting substituents R%=SO Ar, C(O)Ar, SiMe are
2
2
3
4
,5
known. Bis- and tris(alkylamino)phosphines 1 are in general little-studied compounds. Many
years ago Michaelis described an attempt to prepare the tris(n-propylamino)phosphine however
he came to the conclusion that tris(alkylamino)phosphines are unstable. Therefore, we have
6
studied compounds 1 bearing at the nitrogen, not only in chiral 1-methylbenzylamino groups,
but also in other alkyl groups. The compounds 1 were prepared by reaction of PCl or RPCl2
3
7
with excess alkylamines or with alkylamines and triethylamine as shown in Scheme 1.
Aminophosphines 1 are stable at room temperature and not stable to heating. Sterically
hindered groups R and R% increase the stability of 1, which can easily be isolated as
8
spectroscopically pure liquids or crystalline compounds. (Table 1).
Table 1
Phosphorus–nitrogen diad prototropy 1 X 2
1
III IV
Entry Compd
R
R%
Solvent
lP(III)
lHP
JHP KT
P /P
1
2
3
4
5
6
7
8
9
0
1
2
1a
1a
1a
1a
1b
1c
1d
1e
1f
C H5
CH(CH )C H CDCl3
60.04
60.24
60.04
60.11
61.39
60.11
88.65
104.8
115.7
94.24
92.35
88.72
13.63
534
525
528
520
526
538
0.59
37:63
40:60
42:58
56:44
47:53
62:38
95:5
1:11
7:5
47:53
67:33
92:8
6
3
6
5
C H5
CH(CH )C H CD Cl2
8.27
12.14
11.03
14.67
12.15
−7.27
7.53
12.49
5.52
8.31
0.66
0.72
1.28
0.89
1.63
6
3
6
5
2
C H5
CH(CH )C H C D6
6
3 6 5 6
C H5
CH(CH )C H Et O
3 6 5 2
6
4-Me NC H
CH(CH )C H CDCl3
2
6
4
3 6 5
4-FC H4
CH(CH )C H CDCl3
3 6 5
6
C(CH3)3
CH(CH )C H C D6
596 19
3
6
5
6
NHCH(CH )C H CH(CH )C H CDCl3
NHCH CH(CH ) CH CH(CH ) CDCl3
NHCH(CH3)2
NHCH(CH )C H CH(CH )C H CDCl3
580
579
560
562
0.09
1.4
0.89
2.03
3
6
5
3
6
5
2
3 3
2
3 3
1
1
1
1g
1h
1i
(CH ) CH
CDCl3
3 2
3
2
5
3
2
5
NHC(CH3)3
C(CH3)3
CDCl3
−7.24
581 11.5
NMR spectra allow us to observe NH–phosphine and PH–iminophosphorane tautomeric
3
1
forms (Fig. 1). Thus, the P NMR spectrum of tris[(S)-a-methylbenzylamino]phosphine 1e
3
exhibits two signals: the first at 104.2 ppm, quartet, J 18 Hz, belonging to the NH–phosphine
PH
1
form, and the second at 7.53 ppm, double triplet with a very large coupling constant J 580
PH
3
1
31
1
Figure 1. (a) P NMR spectrum of tris[(S)-a-methylbenzylamino]phosphine 1e in CDCl solution; (b) P-{ H} NMR
3
spectrum of 1e in CDCl solution; (c) MOPAC-97 molecular modelling of 1e X 2e
3

7999
3
Hz (PH-group) and the coupling constant J 10 Hz (PNH groups) corresponding to the
PH
3
1
1
PH–iminophosphorane form. In the P-{ H} NMR spectra the double triplet converts into a
1
singlet that confirms the structure of the PH–iminophosphorane 2e (Fig. 1b). The H NMR
1
spectra show a doublet with the same constant J belonging to the PH group. The IR spectra
PH
−
1
of compounds 2 reveal the absorption at 2380 cm , corresponding to the P–H vibration.
The results presented in Table 1 show that the position of the prototropic equilibrium 1 X 2
depends strongly on the solvent used and substituents at the phosphorus and nitrogen atoms,
which, evidently, influence the mutual acidity of the PH and NH forms:
1
. Electron-donating substituents X=F<H<Me N of the para-substituted bis(alkyl-
2
amino)arylphosphines 1a–c, 4-XC H P(NHR%) , displace the prototropic equilibrium 1 X 2
6
4
2
towards the NH–phosphine form (entries 1, 5, 6). Evidently, these substituents reduce the
acidity of the PH-form;
2
. Branched alkyl substituents at the nitrogen atom of compounds 1d–i, R%=(CH ) C>
3
3
CH CH (CH )CHꢀ(CH ) CH>(CH ) CHCH >C H (CH )CH, stabilize the NH–phosphine
3
2
3
3 2
3 2
2
6
5
3
form and displace the tautomeric equilibrium towards this form (entries 8–12). It is well
known that more branched alkyl groups possess a higher electron-donating effect and
9a,b
therefore they reduce the NH-acidity of compounds.
3
. The position of the tautomeric equilibrium depends also on the solvent. In the following
solvent sequence: chloroform>methylene chloride>benzene>ether, the tautomeric equilibrium
is shifted towards the PH–iminophosphoranes 2 (entries 1–4).
The chemical properties of compounds 1 are similar to those of other trivalent phosphorus
compounds, confirming their structure (Scheme 2).
Scheme 2. (a) MeI; (b) Na CO /H O; (c) HCO H; (d) (Me Si) O ; (e) S /toluene
2
3
2
2
3
2
2
8
Compounds 1 are alkylated by methyl iodide to furnish phosphonium salts 3, the alkaline
hydrolysis of which results in the formation of the optically active amidophosphinates 4. The
major diastereomer (S,S )-4a was isolated and purified by crystallization from hexane. The
P
reaction of aminophosphines 1 with formic acid resulted in amides of phosphinic acid 5 with
very high stereoselectivity. The compounds 1 are easily oxidized by bis(trimethylsilyl)peroxide or
add sulfur with the formation of PꢀS or PꢀO derivatives 6, 7. As a result of these reactions a
number of optically active compounds 3–7 bearing chiral (S)- or (R)-1-methylbenzylamino
groups have been prepared. These compounds have been studied as catalysts for asymmetric
reduction of CꢀO and CꢀN groups as well as a chiral matrix for preparation of optically active
dendrimers. The results of these studies will be reported separately.

8000
Acknowledgements
This work was supported by the INTAS-International Association (Project INTAS 97-2120).
References
1
2
3
. Kolodiazhnyi, O. I. Tetrahedron: Asymmetry 1998, 9, 1279.
. Kolodiazhnyi, O. I.; Sheiko, O.; Grishkun, E. V. Heteroatom Chem. 2000, 11, 138–143.
. Kolodiazhnyi, O. I.; Grishkun, E. V.; Sheiko, S.; Demchuk, O.; Thoennessen, H.; Jones, P.; Schmutzler, R.
Tetrahedron: Asymmetry 1998, 9, 1645–1648.
4
5
6
7
. Binder, H.; Fischer, R. Chem. Ber. 1974, 107, 205–209.
. Schmidpeter, A.; Rossknecht, H. Z. Naturforsch. 1970, 25b, 1182.
. Michaelis, A. Lieb. Ann. Chem. 1903, 326, 129.
. As representative example the synthesis of tris(tert-butylamino)phosphine (1i) is described: A solution of phos-
phorus trichloride (0.1 mol) in 10 ml of ether was added dropwise with stirring and cooling up to −70°C to a
solution of tert-butylamine (0.6 mol) in 25 ml of diethyl ether. The temperature was raised to room temperature
and the reaction mixture was left stirring for 2 hours. The triethylamine chlorohydrate was filtered off, the solvent
1
was evaporated and the solid residue was crystallized from diethyl ether at −20°C. Yield 75%, mp 121°C. H NMR
(
l, ppm, J, Hz, CDCl ): 1.26 s [27H, (CH ) C]; 2.46 m (3H, NH).
3 3 3
8
9
. (a) Kolodiazhnyi, O. I. Tetrahedron Lett. 1980, 21, 2269–2272. (b) Tolman, Ch. A. Chem. Rev. 1977, 77, 313.
. The compounds 1, 3–7 are described in: Kolodiazhnyi, O. I.; Prynada, N. Zh. Obshch. Khim, in press. In this paper
we give representative information concerning the compounds 3–7. (3g): Yield 60%, mp 142°C. P NMR (l, ppm,
31
2
0
1
CDCl ): l 41.87. (S,S )-4a: mp 136°C (hexane), [h] −46 (c 0.3, CHCl ), H NMR (l, ppm, J, Hz, CDCl ): 1.11
3
P
P
D
3
3
3
3
d ( J 14, 3H, CH C); 1.11 d ( J
7.5, 3H, CH P); 2.09 m (1H, NH); 3.97 m (1H, CH); 7.28, m (5H, C H ).
HP
3
HH
3
6
5
31
P NMR (l, ppm, CDCl ): l 26.99. (S,R )-4a: l 28.33 ppm. (5d): Yield 80%, ꢀ100% de, bp 140°C (0.05
3
P
P
P
20
1
3
3
mmHg). [h] −91 (c 0.3, toluene). H NMR (l, ppm, J, Hz, CDCl ): 0.93 d [ J 17.5, 9H, (CH ) C]; 1.26 d ( J
D
3
HP
3 3
HP
1
3 HP 6 5
31
9
, 3H, CH CH); 4.27 m (1H, NH); 6.32 d (1H, J 495, PH); 7.28 m (5H, C H ). P NMR (l, ppm, CDCl3).
1
3
1
l : 39.31 dd, J 490, J 17. (6b): Yield 60%, mp 132°C (toluene+hexane). H NMR (l, ppm, J, Hz, CDCl ):
P
HP
HP
3
3
3
HP 3 HP 3 3
1
.25 d ( J 7.5, 3H, CH ); 1.35 d ( J 7.5, 3H, CH ); 2.55 m (2H, CH); 2.99 s (6H, CH N); 4.44 m (2H, NH);
3
1
6
.53–7.84 m (9H, C H +C H ). P NMR (l, ppm, CDCl ): l 64.42. (6c): Yield 50%, mp 106°C (toluene+hexane).
6 5 6 4 3 P
3
1
3
H NMR (l, ppm, J, Hz, CDCl ): 1.28 d ( J 7.0, 3H, CH ); 1.42 d ( J 7.0, 3H, CH ); 2.65 m (2H, CH); 4.3
3
HP
1
3
HP
3
3
m (2H, NH); 6.8–7.7 m (9H, C H +C H ). P NMR (l, ppm, CDCl ): l 62.33. (6e): Yield 60%, mp 105–106°C
ethyl acetate–hexane). H NMR (l, ppm, J, Hz, CDCl ): 1.62 d ( J 6.5, 9H, CH ); 2.52 m (3H, CH); 4.33 m
3H, NH); 7.17 m (15H, C H ); P NMR (l, ppm, CDCl ): l 58.76. (6g): Yield 80%, mp 91–92°C (petrol). H
NMR (l, ppm, J, Hz, CDCl ): 1.13 d ( J 6.5, 12H, CH ); 2.15 m (2H, CH); 3.466 m (3H, NH). P NMR (l,
6
5
6
4
3
P
1
3
3 HP 3
(
(
3
1
1
6
5
3
P
3
31
3
HP
3
1
3
ppm, CDCl ): l 58.76. (7g): Yield 62%, mp 41–42°C (hexane). H NMR (l, ppm, J, Hz, CDCl ): 0.80 d ( J
3
P
3
HP
31
6
.5, 12H, CH ); 2.45 m (2H, CH); 3.41 m (3H, NH). P NMR (l, ppm, CDCl ): l 17.90.
3
3
P
.
.