Mendeleev
Communications
Mendeleev Commun., 2007, 17, 323–324
Synthesis of enantiopure 1,3,4-thiazaphospholes
Lyudmila K. Kibardina, Mikhail A. Pudovik, Vladimir A. Alfonsov* and Olga N. Kataeva
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of
DOI: 10.1016/j.mencom.2007.11.007
Racemic and (R)-(+)-N-trimethylsilyl-(1-phenyl)ethylamines stereoselectively react with O-phenylchloromethylisothiocyanato-
thiophosphonate to give a diastereomeric mixture of separable 1,3,4-thiazaphospholes; racemic thiazaphosphole crystallises as a
conglomerate.
Enantiopure organophosphorus compounds are of interest as
Et N
3
chiral drugs and ligands for the design of homogeneous or
(R)-(+)-PhCH(Me)NH2 + Me3SiCl
–
Et N·HCl
3
1
,2
heterogeneous catalysts. A small number of non-racemic
(
R)-(+)-PhCH(Me)NHSiMe3
compounds with phosphorus being a stereogenic centre have
been reported.1,2 Recently, we studied the reaction of chiral
racemic O-phenylchloromethylisothiocyanatothiophosphonate
2a
Scheme 1
1
with chiral (S)-(–)- and (R)-(+)-(1-phenyl)ethylamine in the
results in the formation of a diastereomeric pair (dP 120.09
3
presence of triethylamine. We found that this reaction proceeds
under very mild conditions with good stereoselectivity and give
and 119.85 ppm) in a 24:76 ratio. Consequently, the diastereo-
3
selectivity is approximately the same, but the separation of
4
-thioxo-1,3,4-thiazaphospholes with the chiral phosphorus atom.
reaction products is more convenient because amine hydro-
chloride is absent from the reaction mixture.
The first step of this reaction is stereocontrolled and includes
amine addition to the isothiocyanate group with the formation
of phosphorylated thiourea. The subsequent intramolecular
nucleophilic replacement of the chlorine atom in the chloro-
methyl group by the sulfur atom of the thiourea fragment takes
place, the chiral centre on the phosphorus atom being preserved.
The stereoselectivity of this reaction is sufficient for the isola-
tion of a predominant diastereomer; however, there are some
complications such as the use of a solvent and a base and
the removal of the precipitate that hampers the isolation of
hydrolytically labile products. To avoid the above difficulties,
we used silylated (1-phenyl)ethylamine, both racemic 2 and
non-racemic 2a in the reaction. Moreover, the bulky trimethyl-
silyl group could increase the stereoselectivity of this reaction.
Racemic silylamine 2 was synthesised according to a published
procedure.4 (R)-(+)-N-Trimethylsilyl-(1-phenyl)ethylamine 2a
was synthesised by the interaction of (R)-(+)-(1-phenyl)ethyl-
amine with trimethylchlorosilane in the presence of triethylamine
S
PhO
P
NCS + (R)-(+)-PhCH(Me)NHSiMe3
ClH C
2
1
2a
Me
H
S
P
S
Me
S
N
H
H
N
C
N
P
P
C N
PhO
Ph
Ph
PhO
Ph
Ph
H
S
ClH C
SiMe3
2
RcRp
3a RcRp
–
Me SiCl
3
S
S
Me
S
Me
H
H
S
H
P
N
C
N
ClH C
C
N
2
H
PhO
N
PhO
SiMe3
RcSp
3
b RcSp
Scheme 2
To obtain the major diastereomer in an enantiopure form,
we studied the reaction of isothiocyanate 1 with silylamine 2a
(Scheme 2) taken in different ratios. The best result was obtained
at the ratio 1:2a = 1:0.7. This reaction easily proceeds under
the same conditions and results in the formation of a mixture of
(
Scheme 1).†
The reaction of isothiocyanate 1 with silylamine 2 proceeds
easily in a diethyl ether solution at room temperature and
†
1
NMR spectra were measured on a Bruker MSL-400 spectrometer, H,
1
3
31
3a and 3b (23:77) with the chemical shifts d of 120.05 and
C and P at 400.13, 100.62 and 162.98 MHz, respectively.
P
2
0
20
119.77 ppm, respectively. Diastereomer 3b crystallised from a
2
a: yield 52%, bp 82 °C (12 Torr), n 1.4918, [a]D +36.2° (c 1.4,
D
1
C H ). H NMR (CDCl ) d: 0.10 (s, 9H, Me Si), 1.44 (d, 3H, MeC,
reaction mixture after 24 h, its angle of the specific rotation was
6
6
3
3
3
[a] +240.5.† Earlier, the structure of 3b and its antipode
20
JHH 7.1 Hz), 4.17 (m, 1H, CH), 7.36 (m, 5H, Ph).
D
2
0
3
3
b: yield 30%, mp 161.5–163 °C, [a]D +240.5° (c 0.87, CH Cl ).
2 2
obtained by a reaction with free amine was studied by X-ray
1
H NMR (CDCl ) d: 1.54 (d, 3H, MeC, 3J 7.0 Hz), 3.49 (dd, 1H,
3
HH
single crystal diffraction. The determination of the unit cell and
2
2
2
2
PCH , J 3.6 Hz, J 13.3 Hz), 3.81 (dd, 1H, PCH , J = J =
HH
=
A
HP
HH
B
HP
the space group of 3b showed that crystallographic parameters
3
3
13.3 Hz), 5.23 (dq, 1H, CHN, JHH = J = 7.0 Hz), 6.79–7.40 (m,
HP
3
are consistent with those reported previously within the limits of
1
3
1
3
0H, 2Ph), 8.28 (s, 1H, NH). C NMR [(CD ) CO] d: 22.37 (Me),
5.18 (d, CH , JPC 56.88 Hz, 1J 144.27 Hz), 55.35 (CH), 122.34
3 2
‡
experimental errors (Figure 1), which is enough to identify 3b.
1
2
CH
o
1
o
1
p
Note that the reaction with a silylated amine in place of a
free amine is more convenient and gives no by-products. The
addition of a crystal of 3b as a seed into the reaction mixture
(C
1
,
JCH 162.3 Hz), 125.23 (C
,
JCH 159.53 Hz), 126.87 (C
, 1JCH 159.53 Hz), 129.23 (C
, J 160.91 Hz), 144.24 (C ), 151.74 (d,
,
PhC
PhOP
PhC
p
m
1J
JCH 160.91 Hz), 127.96 (C
,
PhOP
1
PhC
CH
m
i
159.53 Hz), 129.89 (C
PhOP
CH
PhC
i
2
31
C
, J 9.71 Hz), 167.61 (N=C). P NMR [(CD ) CO] d: 120.67.
PC 3 2
PhOP
–1
‡
IR, n/cm : 685 (P=S), 1210 (POPh), 1570 (C=N), 1590 (Ph), 3275
NH). Found (%): C, 55.47; H, 4.85; N, 8.02; P, 9.32, S, 18.23. Calc. for
C H N OPS (%): C, 55.14; H, 4.93; N, 8.04; P, 8.82; S, 18.41.
X-ray data were obtained with an Enraf Nonius CAD4 diffractometer:
(
a = 5.684(5), b = 15.009(10) and c = 10.492(10) Å, b = 105.1(1)°, V =
3
= 865.2(12) Å , space group P2 , Z = 2.
1
6
17
2
2
1
©
2007 Mendeleev Communications. All rights reserved.
– 323 –
Kibardina, Lyudmila K.
