Stereoselective reactions of optically active derivatives of α-methylbenzylaminophosphine

Article abstract of DOI:10.1023/B:RUGC.0000031849.78207.1c

A number of N-(α-methylbenzyl) phosphorus amides were synthesized, and their stereochemical properties were studied. Reactions of achiral chlorophosphines with optically active α-methylbenzylamine are accompanied by asymmetric induction at the phosphorus

Full text of DOI:10.1023/B:RUGC.0000031849.78207.1c

Russian Journal of General Chemistry, Vol. 74, No. 4, 2004, pp. 515 522. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 4, 2004,
pp. 565 573.
Original Russian Text Copyright
2004 by Kolodyazhnyi, Andrushko, Grishkun.
Stereoselective Reactions of Optically Active Derivatives
of -Methylbenzylaminophosphine
O. I. Kolodyazhnyi, N. V. Andrushko, and E. V. Grishkun
Institute of Bioorganic and Petroleum Chemistry, National Academy of Science of Ukraine, Kiev, Ukraine
Received February 18, 2002
Abstract A number of N-( -methylbenzyl) phosphorus amides were synthesized, and their stereochemical
properties were studied. Reactions of achiral chlorophosphines with optically active -methylbenzylamine are
accompanied by asymmetric induction at the phosphorus atom to give optically active diastereoisomers of N-
( -methylbenzyl)aminophosphines, which were isolated as the corresponding borane complexes with 100%
optical purity. Stereochemically pure (R,S)-aminophosphines were obtained by decomposition of these
complexes via treatment with diethylamine. Their oxidation, sulfurization, and alkylation with methyl iodide
afforded optically active aminophosphine derivatives. Hydrolysis of (R,S)-aminophosphines gave optically
active tert-butylphenylphosphine oxide and phosphonic acid amides. (R,S)- and (S,S)-Diastereoisomers of N-
( -methylbenzyl)phosphinic amides were separated by crystallization and flash chromatography, and their
absolute configuration was established. Also, derivatives of bis- and tris( -methylbenzylamino)phosphines
were synthesized.
-Methylbenzylamine is one of the most important
reagents for stereochemical studies in organic chem-
istry. Numerous optically active derivatives of
-methylbenzylamine were synthesized and used in
various theoretical and applied studies [1 3]. However,
optically active organophosphorus derivatives of
-methylbenzylamine were studied very poorly, while
those containing tervalent phosphorus were unknown
at all prior to our works [3, 4]. Optically acitive phos-
phorus(III) derivatives of -methylbenzylamine attract
interest as starting compounds for the synthesis of
chiral organophosphorus compounds which may be
important as chiral ligands, catalysts, and biologically
active substances. The chemistry of optically active
-methylbenzylaminophosphine derivatives is also
interesting, as follows from the transformations and
properties of these compounds, described in this
article. We have synthesized compounds containing
different numbers of amino groups: N-mono-, N,N -
bis-, and N,N ,N -tris( -methylbenzyl)phosphorus
acid amides, and examined their properties.
Monosubstituted N-( -methylbenzyl)phosphinous
amides were synthesized by reaction of the correspond-
ing phosphorus chlorides with 2 equiv of -methyl-
benzylamine or with a mixture of -methylbenzyl-
amine and triethylamine. The reaction of phosphinous
acid chlorides Ia Ic with a mixture of ( )-(R)-methyl-
benzylamine and triethylamine readily occurs in di-
ethyl ether, benzene, or toluene, yielding N-substi-
tuted phosphinous amides IIa IIc. The reaction is
relatively slow at room temperature, but N-( -methyl-
benzyl)phosphinous amides IIa IIc are formed in
very good yields in 8 12 h.
I, II, R = i-Bu, R = t-Bu (a); R = Ph, R = t-Bu (b); R = Ph, R = 2,4,6-(CH3)3C6H2 (c); B is a base.
N-( -Methylbenzyl)phosphinous amides IIa and
IIb are stable colorless liquids which can be distilled
under reduced pressure. Compounds II can be stored
for a long time with protection from atmospheric
moisture and oxygen. However, they are readily
oxidized with atmospheric oxygen and readily
undergo various transformations, as will be shown
below. Diastereoisomers of compounds IIa IIc were
1070-3632/04/7404-0515 2004 MAIK Nauka/Interperiodica

516
KOLODYAZHNYI et al.
Stereoselectivity of formation of -methylbenzylaminophosphines R(R )PNHCH(Me)Ph (IIa IIc)
Reaction conditions (20 C)
Diastereoisomer
ratioa
Comp. no.
R
R
solvent
Diethyl ether
Benzene
base
IIa
IIb
IIbb
IIb
IIb
IIb
IIb
IIb
IIb
IIc
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
Ph
i-Bu
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Triethylamine
36: 64
10: 90
18: 82
17.5: 82.5
25: 75
42: 58
12: 88
20: 80
38: 62
75: 25
-Methylbenzylamine
Diazabicyclooctane
Diazabicycloundecene
Triethylamine
Toluene
Diethyl ether
Hexane
THF
Benzene
2,4,6-(CH3)3C6H2
a
31
b
Determined by P NMR spectroscopy as average value from 2 3 measurements.
At 70 C.
identified by NMR spectroscopy and high-perfor-
stereoisomers of aminophosphines II at a ratio of
10:1. The mixtures of diastereoisomers were sep-
arated into stereochemically pure (R,S) and (R,R)
compounds through the corresponding borane com-
plexes. For example, the reaction of -methylbenzyl-
aminophosphine IIa with the borane tetrahydrofuran
complex quantitatively afforded crystalline complexes
III which can be isolated with a 100% stereochemical
purity by recrystallization from hexane.
mance liquid chromatography (HPLC). The 31P {1H}
NMR spectra were the most informative: the diastereo-
isomers give rise to sharp peaks at a considerable
distance from each other. The diastereoisomer ratio
depends on the reaction conditions (see table), includ-
ing the nature of the organic base and solvent and
temperature. (R)- and (S)- -Methylbenzylamines give
rise, respectively, to (R,S)/(S,S)- and (S,R)/(R,R)-dia-
Me
Me
H
Ph
Ph
Me
H
Ph
NH
NH
NH
BH3/THF
Et2NH
H
H3B
Ph
Ph
t-Bu
t-Bu
Ph
(R,S)-IIIb
t-Bu
(R,S)-IIb + (S,S)-IIb
(R,S)-IIb, 100% de
Treatment of a mixture of (R,S) and (S,S) diastereo-
isomers of IIb with the BH3 THF complex gave the
only diastereoisomer of phosphine borane complex
III. Its structure and stereochemical purity were
completed by heating a solution of the complex in di-
ethylamine for 16 h at 50 C. The resulting diastereo-
isomerically pure product was identical to the initial
aminophosphine (a mixture of diastereoisomers)
according to the 31P NMR spectrum of a mixture of
the two samples. Optically pure tert-butyl( -methyl-
benzylamino)phenylphosphine (IIb) is a colorless
liquid which can be distilled under reduced pressure
without appreciable decomposition.
1
confirmed by the H, 13C, and 31P NMR spectra. The
chemical shift of the phosphorus atom in III is equal
to +70 ppm; its signal appears as a broadened doublet
due to coupling with 11B. The 1H and 13CNMR spectra
of III contain signals from all hydrogen and carbon
atoms present in the molecule. There were no signals
indicating the presence of other diastereoisomers.
N-Phosphorylated amines IIa IIc are convenient
initial compounds for the preparation of stereochem-
ically pure chiral reagents. Oxidation of aminophos-
phines IIa and IIb with hydrogen peroxide in dioxane
occurs in a stereospecific fashion and gives amino-
phosphine oxides IVa IVc in very good yields.
The phosphine borane complex was decomposed
by treatment with excess diethylamine. This reaction
is stereospecific, and configuration of the phosphorus
atom is retained [5 8]. The process is fairly slow: it is
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STEREOSELECTIVE REACTIONS OF OPTICALLY ACTIVE DERIVATIVES
517
benzylamino)phenylphosphine (IIb) in aqueous di-
oxane at 80 C was complete in 12 h; the reaction
afforded optically active ( )-(S)-tert-butyl( -methyl-
benzylamino)phenylphosphine oxide (VII). The
acidolysis of phosphinous amide IIb with formic acid
in toluene at 0 C took 15 30 min and afforded the
same optically active product VII. Unlike tervalent
phosphorus compounds II, phosphorus(V) derivatives
IV and V are very stable to hydrolysis; they do not
change on heating for 48 h in boiling aqueous dioxane
containing 0.1 N sulfuric acid [9]. This reaction
provides a convenient procedure for the preparation
of (S)- and (R)-enantiomers of tert-butyl(phenyl)phos-
phine oxide from accessible tert-butylchlorophosphine
and (S)- and (R)-enantiomers of -methylbenzylamine.
(S)- and (R)-Enantiomers of tert-butyl(phenyl)phos-
phine oxide are relatively difficultly accessible com-
pounds. The known methods for their synthesis
include a number of steps, and they cannot be re-
garded as preparative [10 12]. The specific optical
rotation and other physical parameters of product VII
coincided with the data reported in [10, 11].
S
P
O
P
R
NHR*
R
R
NHR*
t-Bu
R
H2O2
S8
Va Vc
Va, Vb
IIa IIc
Me
P
O
P
HCO2
MeI
I
+
Ph
H
NHR*
t-Bu
VI
t-Bu
VII
R* = (S)-CH(Me)Ph; R = i-Bu, R = t-Bu (a); R = Ph, R =
t-Bu (b); R = Ph, R = 2,4,6-(CH3)3C6H2 (c).
The (S,S)- and (R,S)-diastereoisomers of amino-
phosphine oxide IVb were identified by the 31P NMR
spectra. Their ratio and purity were checked by HPLC.
The major (R,S)-diastereoisomer was characterized by
greater retention time, and the minor (S,S)-isomer left
the column first. No appreciable difference in the
ratios of diastereoisomers, determined from the 31P
NMR and HPLC data, was observed. Diastereo-
isomeric products IV were separated by flash chro-
matography using 50-cm columns packed with silica
gel (Merck) and a 92:8 mixture of hexane with iso-
propyl alcohol as eluent. Fractions containing dif-
ferent diastereoisomers were analyzed by HPLC. We
succeeded in separating the diastereoisomers com-
pletely and isolating them in the pure state. The
subsequent recrystallization gave compounds IV with
a diastereoisomeric purity of 100% (according to the
1H and 31P NMR data). Their NMR spectra contained
singlets from the tert-butyl groups (without any dou-
The absolute configurations of the products were
established by X-ray analysis, chemical transforma-
tions, and chemical correlation. The absolute con-
figuration of the (S,S)-diastereoisomer of aminophos-
phine oxide IV was determined on the basis of the
X-ray diffraction data. The results allowed us to
assign (RP)-configuration to initial aminophosphine II
and (S)-configuration to the sulfurization, alkylation,
and hydrolysis products (compounds V VII). These
reactions are stereospecific, and they follow SN2
mechanism with inversion of configuration at the
phosphorus atom [13, 14]. The (S)-configuration of
hydrolysis product VII was also confirmed by the
negative optical rotation value.
1
bling). The H NMR spectrum of tert-butyl(isobutyl)-
The amino group in compound (S,SP)-(+)-(IVc) is
replaced by methoxy group on heating for 5 h in
boiling methanol containing sulfuric acid. As a result,
previously reported methyl ( )-(R)-mesityl(phenyl)-
phosphinate [9] was obtained with an ee (enantiomeric
excess) value of 75%. In keeping with the negative
optical rotation value, the phosphorus configuration in
the initial amide should be SP, for SN2 substitution
is accompanied by inversion of configuration [14].
-methylbenzylaminophosphine oxide (IVa) revealed
magnetic nonequivalence of some protons, specifically
of the methyl protons in the isobutyl group.
By sulfurization of compounds IIa and IIb we ob-
tained aminophosphine sulfides Va and Vb as mix-
tures of two diastereoisomers which are clearly dis-
tinguished by HPLC and NMR. The major diastereo-
isomer of Vb was isolated and purified by recrystal-
lization from hexane. The product (colorless needles)
had a diastereoisomeric purity of 100%. The minor
stereoisomer of Vb was isolated as a colorless viscous
liquid containing 20% of the major isomer which
could not be separated by crystallization and column
chromatography. N-Phosphorylated amine IIa is
readily alkylated with methyl iodide to give phos-
phonium salt VI.
Interesting chemical properties are exhibited by
chiral phosphorus(III) bis- and tris(alkylamides) VIII
and X which exist in equilibrium with tautomeric
iminophosphoranes IX and XI, as we reported pre-
viously [15, 16]. Phosphorous tris( -methylbenzyl-
amide) (VIII) was synthesized by reaction of 3 equiv
of -methylbenzylamine with phosphorus(III) chloride
in the presence of triethylamine in toluene. Alkyl-
and arylphosphonous bis( -methylbenzylamides)
The hydrolysis of (RP,S)-tert-butyl( -methyl-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004

518
KOLODYAZHNYI et al.
Xa Xe were prepared by treatment of the correspond-
ing alkyl- and aryldichlorophosphines with 2 equiv of
-methylbenzylamine in toluene in the presence of
excess triethylamine. The procedures for the synthesis
of phosphorus(III) amides VIII and X and their spec-
tral parameters were reported by us previously [4].
Et3N
PCl3 + 3H2NR
Et3N HCl
P(NHR )3
(R NH)2P(H)=NR
VIII
IX
R = (S)-CH(CH3)C6H5.
H
R
H
R
Et3N
RPCl2 + H2NR
RP(NHR )2
Xa Xe
P
P
Et3N HCl
NR
R NH
NHR
R N
XIa XIe
R = Ph (a), 4-C6H4F (b), 4-Me2NC6H4 (c), Me (d), t-Bu (e); R = (S)-CH(CH3)C6H5.
In this work we examined some chemical trans-
H
P
H
P
formations of compounds VIII and X. Insofar as
these compounds are unstable, they were brought into
further reactions without isolation or the reaction
mixture was filtered and evaporated under reduced
pressure. The residue obtained after evaporation was
spectroscopically pure compound VIII or X which
was then treated with appropriate reagent, and the
products were characterized as stable derivatives.
Phosphorous tris( -methylbenzylamide) (VIII) readily
reacts with borane in THF to give stable borane com-
plex XVf. Phenylphosphonous bis( -methylbenzyl-
amide) (Xa) was oxidized with hydrogen peroxide to
obtain the corresponding phosphine oxide XIIa in
quantitative yield. Compounds Xa Xc took up
elemental sulfur in toluene or benzene solution with
formation of crystalline phosphine sulfides XIIIa
XIIIc. The reactions were carried out with equimolar
amounts of the reactants, for the use of excess sulfur
strongly impairs the purity of the products. Bisamides
X readily undergo acidolysis and hydrolysis, yielding
phosphinic amides XIVd and XIVe. These reactions
smoothly occurred with formic acid in toluene.
R
N R
N R
R
N R
N R
S
O
H
H
S8
H2O2
XIIa
XIIIa XIIIc
VIII, X
HCO2H
BH3 THF
H
H
R
N R
N R
N R
R
.
...
. .
O=P
P
BH3
H
H
XVf
XIVd, XIVe
R = Ph (a), 4-C6H4F (b), 4-Me2NC6H4 (c), Me (d), t-Bu
(e), (S)-NHCH(CH3)C6H5 (f); R = (S)-CH(CH3)C6H5.
The reaction of trimethylsilylmethylphosphonous
bis( -methylbenzylamide) with formic acid was ac-
companied by desilylation of intermediate monoamide
XVI to give methylphosphinic amide XIVd [17]. The
same product was obtained by acidolysis of phos-
phorous diamide Xd.
H
H
H
H
N R*
N R*
N R*
N R
N R*
HCO2H
HCO2H
O
P
MeP
H
Me3SiCH2P
H
O
P
CH3
CH2SiMe3
H
N R*
H
XVI
XIVd
Xd
R* = (S)-CH(CH3)C6H5.
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STEREOSELECTIVE REACTIONS OF OPTICALLY ACTIVE DERIVATIVES
519
The high stereoselectivity of this transformation is
worth noting. N-( -Methylbenzyl)methylphosphinic
amide (XIVd) was isolated as a single diastereoisomer
(according to the NMR spectra). Phosphinic amides
XIVd and XIVe are stable substances which can be
purified by vacuum distillation or crystallization.
temperature and was left overnight. The precipitate of
triethylamine hydrochloride was filtered off and
washed with 50 ml of diethyl ether. The filtrate was
evaporated, and the residue was distilled under
reduced pressure. The reaction was carried out under
different conditions. Depending on the nature of the
base and solvent, different diastereoisomer ratios were
obtained. Yield 80%. Colorless liquid, bp 130 135 C
1
Their H and 31P NMR spectra contain a doublet with
a direct P H coupling constant of 490 500 Hz.
1
(0.02 mm). H NMR spectrum (CDCl3), , ppm (J,
3
EXPERIMENTAL
Hz): 0.77 d [(CH3)3C, JHP 5.0], 0.81 d [(CH3)3C ,
3
3JHP 7.0], 1.60 m (CH), 1.45 d (CH3, JHH 7.0),
3
The melting points were not corrected. The NMR
spectra were recorded on Varian VXR-300 (300 MHz
1.51 d (CH3, JHH 7.0), 3.54 m (NH), 7.10 7.33 m
(C6H5). 31P NMR spectrum (CDCl3), P, ppm: 49.9,
47.24 (diastereoisomer ratio 8:92). Found P, %:
10.61. C18H24NP. Calculated P, %: 10.85.
1
for H and 126.16 MHz for 31P) and Jeol (90 MHz)
spectrometers. The chemical shifts are given in the
scale (ppm) relative to tetramethylsilane (internal
(SP)-tert-Butyl( -methylbenzylamino)phenyl-
phosphine borane complex (III). A solution of
0.3 mol of BH3 in tetrahydrofuran was added to a
solution of 0.1 mol of (SP)/(RP)-tert-butyl( -methyl-
benzylamino)phenylphosphine in 5 ml of THF. The
resulting transparent solution was evaporated under
reduced pressure to isolate a crystalline product which
was recrystallized from hexane. Yield 90%, mp 140
141 C (from hexane), [ ]D +24.5 (c 0.01,
CH2Cl2). 1H NMR spectrum (CDCl3), , ppm (J, Hz):
1
reference, H) and 85% H3PO4 (external reference,
31P). HPLC analysis was performed on Milikhrom-1A
(Russia) and LKB (Sweden) instruments under the
following conditions: Ultrapack TSK-ODS-120-T
(5 m), column 250 4.6 mm, eluent 65 75%
aqueous methanol; Silasorb DEA, column 120 2 mm,
hexane 2-propanol, 95:5; Silasorb C-18, column
120 2 mm, 50% aqueous acetonitrile; UV detector,
260 nm. Silicagel L 100/160 m (Chemapol,
Czechia) was used for column chromatography. All
operations were carried out under argon. The solvents
were preliminarily distilled in an inert atmosphere
from P2O5 (diethyl ether, hexane, heptane, benzene,
CCl4), metallic sodium (methanol, triethylamine), or
CaCl2 (ethyl acetate). ( )-(S)- -Methylbenzylamine
and (+)-(R)- -methylbenzylamine were commercial
chemicals (Merck); they were used without additional
puification.
3
0.2 2 m (3H, BH3), 1.01 d [9H, (CH3)3C, JHP
3
14.16], 1.50 d (3H, CH3, JHH 6.72), 2.07 br.d (1H,
2
NH, JHP 16.0), 4.45 m (1H, CHN), 7.10 7.40 m
(10H, C6H5). 13C NMR spectrum (CDCl3), C, ppm
2
(J, Hz): 24.57 d [(CH3)3C, JCP 2.76], 25.57 d
3
1
[(CH3)CHN, JCP 5.20], 30.69 d [(CH3)3C, JCP
2
43.40], 52.47 d (CHN, JCP 2.01), 126.10 s,
126.94 s, 127.58 d (JCP 9.50), 130.37 d (JCP 2.50),
130.75 d (JCP 46.80), 131.94 d (JCP 9.40) (C6H5).
31P NMR spectrum (CDCl3), P, ppm (J, Hz): 69.76 d
(1JBP 42.93). Found, %: N 4.85; P 10.61. C18H27
BNP. Calculated, %: N 4.68; P 10.35.
tert-Butyl(isobutyl)- -methylbenzylaminophos-
phine (IIa). A solution of 0.02 mol of -methyl-
benzylamine in 5 ml of benzene was added with stir-
ring to a solution of 0.02 mol of tert-butyl(chloro)iso-
butylphosphine and 3.5 ml of triethylamine in 10 ml
of benzene. The mixture was stirred for 2 3 h at room
temperature and was left overnight. The precipitate of
triethylamine hydrochloride was filtered off and
washed with diethyl ether. The filtrate was evaporated,
and the residue was distilled under reduced pressure.
Yield 70%. Colorless liquid, bp 85 90 C (0.08 mm).
31P NMR spectrum (CDCl3), P, ppm: 51.13, 50.035.
Found P, %: 11.82. C16H28NP. Calculated P, %: 11.67.
(SP,S)-tert-Butyl( -methylbenzylamino)phenyl-
phosphine (IIb). A solution of 0.1 mol of complex
III in 3 ml of diethylamine was left to stand overnight
at 50 C. The solvent was distilled off, and the residue
was distilled in a high vacuum. The 31P NMR spec-
trum of the product contained only one signal belong-
ing to the (SP)-diastereoisomer, which was confirmed
by comparison with the spectrum of an artificial mix-
ture of diastereoisomers (10:1). Yield 50%, bp 160
1
161 C (0.02 mm). H NMR spectrum (CDCl3),
,
(SP,S)/(RP,S)-tert-Butyl( -methylbenzylamino)-
phenylphosphine (IIc). A solution of 0.02 mol of
( )-(S)- -methylbenzylamine and 0.022 mol of tri-
ethylamine in 5 ml of toluene was slowly added (over
a period of 3 h) with stirring to a solution of 0.02 mol
of tert-butyl(chloro)phenylphosphine in 10 ml of
toluene. The mixture was stirred for 2 3 h at room
3
ppm (J, Hz): 0.81 d [9H, (CH3)3C, JHP 7.0],
3
1.60 m (1H, NH), 1.45 d (3H, CH3, JHH 14.0),
3.54 m (1H, CHN), 7.10 7.33 m (10H, C6H5). 31P
NMR spectrum (CDCl3):
49.00 ppm.
P
Mesityl( -methylbenzylamino)phenylphosphine
(IIc) was synthesized as described above for com-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004

520
KOLODYAZHNYI et al.
pound IIa. Yield 85%. Filtration of the reaction mix-
ture, followed by removal of the solvent, gave a
viscous liquid which could not be distilled under
reduced pressure. The product was characterized by
spectral data and was brought into further transforma-
tions without additional purification. 31P NMR spec-
trum (CDCl3), P, ppm: 29.75, 29.23.
JPH 9.0), 4.5 m (1H, PhCHMe), 6.9 d (2H, 3-H, 5-H,
JPH 4.0), 7.2 7.4 m (5H, C6H5), 7.35 m (5H, C6H5).
31P NMR spectrum (CDCl3):
28.0 ppm [9].
P
Alcoholysis of (+)-(SP,S)-mesityl( -methylben-
zylamino)phenylphosphine (IIc). A mixture of
18.2 mmol of (+)-(SP,S)-mesityl( -methylbenzyl-
amino)phenylphosphine, 85 ml of methanol, and
1.6 ml of 98% sulfuric acid was heated for 5 h under
reflux. The mixture was cooled, 200 ml of chloroform
was added, and the mixture was washed with a 10%
aqueous solution of sodium hydrogen carbonate
(3 50 ml) and water (2 50 ml). The organic phase
was dried over magnesium sulfate and concentrated
under reduced pressure. The residue was a colorless
liquid (6.17 g) which was purified by flash chromato-
graphy on silica gel. We thus isolated methyl ( )-(R)-
phenyl(2,4,6-trimethylphenyl)phosphinate as a color-
less liquid. Yield 4.0 g (80%), [ ]D 20 (c 0.33,
tert-Butyl(isobutyl)( -methylbenzylamino)phos-
phine oxide (IVa) was synthesized as described
below for compound IVb. Yield 64%, mp 171 172 C
(from diethyl ether); [ ]D 44.8 (c 1, benzene).
1H NMR spectrum (CDCl3), , ppm (J, Hz): 1.00 m
[6H, (CH3)2C], 1.12 d [9H, (CH3)3C, JHP 20],
1.53 d (3H, CH3, JHH 6.5), 1.51 m (2H, CH2),
2.08 m (1H, CHC), 4.57 d (1H, NH), 7.00 7.31 m
(5H, C6H5). 31P NMR spectrum (CDCl3):
P
52.92 ppm. Found, %: N 4.96; P 10.81. C16H28NOP.
Calculated, %: N 4.98; P 11.01.
1
ethanol) [9]. H NMR spectrum (CDCl3), , ppm (J,
(S,S)/(S,R)-tert-Butyl( -methylbenzylamino)-
phenylphosphine oxide (IVb). Excess carbon tetra-
chloride was added on cooling to a solution of amino-
phosphine IIb in diethyl ether. The mixture was
allowed to warm up to room temperature and cooled
again, and excess methanol was added. The mixture
was left to stand for 1 h and evaporated. The residue
was a viscous liquid which was diluted with hexane,
and the mixture was left to stand overnight for crystal-
lization. The crystalline product was filtered off and
recrystallized from ethyl acetate. The mother liquor
was evaporated, and the residue was subjected to
column chromatography on silica gel using hexane
2-propanol (92:8) as eluent.
Hz): 2.3 s (3H, 4-CH3), 2.50 d (6H, 2-CH3, 6-CH3,
JPH 1.2), 3.70 d (3H, OCH3, JPH 11.1), 6.90 d (2H,
3-H, 5-H, JPH 4.2), 7.5 m (3H, C6H5), 7.60 m (2H,
C6H5). 31P NMR spectrum (CDCl3):
37.0 ppm.
P
tert-Butyl( -methylbenzylamino)phenylphos-
phine sulfide (Vb). To a solution of aminophosphine
IIb in benzene, cooled to 0 5 C, we added a solution
of 1.1 equiv of sulfur in benzene. The mixture was
allowed to warm up to room temperature and was left
to stand for 1 h. The solvent was evaporated to obtain
a viscous liquid which was diluted with hexane and
was left overnight for crystallization. The crystalline
product was filtered off and recrystallized from ethyl
acetate. The mother liquor was evaporated, and the
residue was subjected to column chromatography on
silica gel using hexane 2-propanol (92:8) as eluent.
(SP,S)-Diastereoisomer. Yield 50%, mp 105 106 C
(R,R)-Diastereoisomer. Yield 5%, mp 142
1
144 C, [ ]D 125.5 (c 1, heptane). H NMR spec-
trum (CDCl3), , ppm (J, Hz): 1.04 d [9H, (CH3)3C,
J 14.4], 1.48 d (3H, CH3C, J 7.4), 2.76 d.d (1H, NH,
J 7), 2.99 m (3H, CH3C), 4.17 br (1H, CH), 7.13
1
(from hexane), [ ]D 66 (c 1, CHCl3). H NMR
7.57 m (10H, C6H5). 31P NMR spectrum (CDCl3),
,
spectrum (CDCl3), , ppm (J, Hz): 0.98 d [9H,
(CH3)3C, JHP 16.6], 1.21 d (3H, CH3, JHH 6), 2.21 br
(1H, NH), 4.67 d.d (1H, CH, JHP 6.6), 7.2 m and
P
ppm: 42.86. (S,R)-Diastereoisomer. Yield 70%, mp
171 172 C (from ethyl acetate), [ ]D 82.5 (c 0.5,
7.93 m (10H, C6H5). 31P NMR spectrum (CDCl3):
80.74 ppm. (RP,S)-Diastereoisomer. Yield 8%. H
1
ethanol). H NMR spectrum (CDCl3), , ppm (J, Hz):
P
1
1.01 d [9H, (CH3)3C, JHP 14.8], 1.33 d (3H, CH3,
JHP 7.0), 2.80 br (1H, NH), 4.44 br (1H, CH, JHH 8.0),
7.19 7.4 m and 7.87 m (10H, C6H5). 31P NMR spec-
NMR spectrum (CDCl3), , ppm (J, Hz): 0.98 d
[(CH3)3C, JHP 16.6], 1.21 d (CH3, JHH 6.0), 2.21 m
(NH), 4.41 d.d (CH, JHH 6.0, JHP 8), 7.2 m and
trum (CDCl3):
41.32 ppm. Found, %: N 4.67; P
P
7.93 m (C6H5). 31P NMR spectrum (CDCl3):
10.42. C18H24NOP. Calculated, %: N 4.65; P 10.28.
P
78.10 ppm. Found, %: N 4.45; P 9.62. C18H24NPS.
Calculated, %: N 4.41; P 9.76.
Mesityl( -methylbenzylamino)phenylphosphine
oxide (IVc) was synthesized as described above for
compound IVb. (S,SP)-Diastereoisomer. Yield 50%,
mp 157 C (from ethyl acetate), [ ]D +10 (c 1,
tert-Butyl(isobutyl)- -methylbenzylaminophos-
phine sulfide (Va) was synthesized as described
above for compound Vb. Yield 40%, mp 116 117 C
1
ethanol). H NMR spectrum (CDCl3), , ppm (J, Hz):
1
1.67 d (3H, PhCHMe, JHH 7), 2.29 s (3H, 4-Me),
2.38 s (6H, 2-Me, 4-Me), 3.00 m (1H, NH, JHH 9.0,
(from diethyl ether). H NMR spectrum (CDCl3), ,
ppm (J, Hz): 0.74 d [6H, (CH3)2C, JHH 6.6],
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004

STEREOSELECTIVE REACTIONS OF OPTICALLY ACTIVE DERIVATIVES
521
1.19 d [9H, (CH3)3C, JHP 16.2], 1.49 d (3H, CH3, JHH
6.6), 1.63 m (2H, CH2P), 2.04 br (1H, CHC), 4.73 br
(1H, CHN), 7.26 m and 7.34 m (5H, C6H5). 31P NMR
(Xa). A solution of 0.01 mol of dichloro(phenyl)-
phosphine in 10 ml of diethyl ether was added drop-
wise with stirring to a solution of 0.02 mol of ( )-(S)-
-methylbenzylamine and 0.02 mol of triethylamine
in 10 ml of diethyl ether, cooled to 70 C. The mix-
tue was allowed to warm up to room temperature and
was stirred for 2 h. The precipitate of triethylamine
hydrochloride was filtered off, and the filtrate was
evaporated. The residue was phenylphosphonous bis-
( -methylbenzylamide) (Xa) as a viscous oil. Yield
spectrum (CDCl3):
84.58 ppm. Found N, %: 4.8.
C16H28NPS. CalculatPed N, %: 4.91.
(SP,S)-tert-Butyl(methyl)( -methylbenzylamino)-
phenylphosphonium iodide (VI). Methyl iodide,
0.015 mol, was added to a solution of 0.01 mol of tert-
butyl( -methylbenzylamino)phenylphosphine in 5 ml
of toluene, and the mixture was left overnight. The
product was filtered off and recrystallized. Yield 84%,
mp 220 221 C (from C2H5OH H2O, 1:10), [ ]D 7.3
(c 2.5, C2H5OH). 1H NMR spectrum (CDCl3), , ppm
(J, Hz): 1.21 d [9H, (CH3)3C, JHP 16], 1.51 d (3H,
CH3, J 6.5), 2.45 d (3H, CH3P, JHP 11.5), 4.11 br (1H,
CH), 6.14 br (1H, NH), 7.30 m (10H, C6H5). 31P
95%. 31P NMR spectrum (CDCl3):
(cf. [4]).
60.1 ppm
P
Phenylphosphonic bis( -methylbenzylamide)
(XIIa). Compound Xa was synthesized as described
above. After removal of the solvent, the residue was
dissolved in anhydrous dioxane, the solution was
cooled to 20 C, a solution of 0.0125 mol of hydro-
gen peroxide in 10 ml of dioxane was added, and the
mixture was left to stand for 1 h. The solvent was
removed under reduced pressure, and the residue was
NMR spectrum (CDCl3):
55.8 ppm. Found, %: N
P
3.33; P 7.29. C19H27INP. Calculated, %: N 3.28; P
7.25. Compound VI was converted into readily crys-
tallizable perchlorate. For this purpose, it was dis-
solved in a minimal amount of water, and an aqueous
solution of sodium perchlorate was added. The pre-
cipitate was filtered off and purified by recrystalliza-
tion.
1
recrystallized from hexane. Yield 80%, mp 70 C. H
NMR spectrum (CDCl3), , ppm (J, Hz): 1.25 d (3H,
3
3
CH3, JHH 7.0), 1.42 d (3H, CH3, JHH 7.0), 2.65 m
(1H, NH), 2.79 m (1H, NH), 4.3 m (1H, CH), 4.5 m
(1H, CH), 6.8 7.5 m (15H, C6H5). 31P NMR spectrum
(CDCl3): P 19 ppm. Found N, %: 7.40. C22H25N2OP.
Calculated N, %: 7.68.
(SP,S)-tert-Butyl(methyl)( -methylbenzylamino)-
phenylphosphonium perchlorate. Yield 60%, mp
242 243 C (from C2H5OH H2O, 1:10). 1H NMR
spectrum (CDCl3), , ppm (J, Hz): 1.11 d [9H,
(CH3)3C, JHP 21], 0.99 m (2H, CH2), 1.85 d (3H, CH3,
JHH 8), 2.77 m (3H, CH3P), 3.77 m (1H, CHC),
5.89 d (1H, NH), 7.05 7.26 m (5H, C6H5). 31P NMR
Phenylphosphonothioic bis( -methylbenzyl-
amide) (XIIIa). Crude compound Xa (see above) was
dissolved in benzene, an equimolar amount of finely
powdered elemental sulfur was added, and the mixture
was left overnight. The solvent was removed under
reduced pressure, and the residue was purified by
column chromatography on silica gel using hexane
ethyl acetate (5:1) as eluent. Yield 80%, yellowish
oily substance. 1H NMR spectrum (CDCl3), , ppm (J,
spectrum (CDCl3):
57.48 ppm. Found N, %: 3.44.
P
C19H27ClNO4P. Calculated N, %: 3.50.
( )-(S)-tert-Butylphenylphosphine oxide (VII).
A solution of 0.01 mol of formic acid was added
dropwise with stirring to a solution of 0.01 mol of
(SP,S)-tert-butyl( -methylbenzylamino)phenylphos-
phine in 10 ml of toluene, cooled to 50 C. The mix-
ture was allowed to warm up to room temperature and
was left to stand for 1 h. The precipitate was filtered
off, the filtrate was evaporated under reduced pressure,
and the residue was extracted with hexane. The extract
was evaporated to obtain spectroscopically pure com-
pound VII which may be purified (if necessary) by
column chromatography on silica gel using benzene
as eluent. The product is readily oxidized on exposure
to air. Yield 80%, [ ]D 44.6 (c 1, toluene); pub-
3
Hz): 1.25 d (3H, CH3, JHH 7.0), 1.42 d (6H, CH3,
3JHH 7.0), 2.65 m (2H, CH), 4.3 m (2H, NH), 6.8
7.5 m (15H, C6H5). 31P NMR spectrum (CDCl3):
P
65 ppm. Found, %: N 7.11; S 8.45. C22H25N2PS.
Calculated, %: N 7.35; S 8.43.
p-Fluorophenylphosphonothioic bis( -methyl-
benzylamide) (XIIIb) was synthesized as described
above for compound XIIIa. Yield 50%, mp 105
106 C (from toluene hexane, 5:1), [ ]D 28.18 (c 1,
1
CHCl3). H NMR spectrum (CDCl3), , ppm (J, Hz):
1.28 d (CH3, JHH 7.0), 1.42 d (CH3, JHH 7.0), 2.65 m
(CH), 4.3 (NH), 6.8 7.7 m (C6H5). 31P NMR spec-
1
lished data [10 12]: [ ]D 40.45 (c 1.78, MeOH). H
NMR spectrum (CDCl3), , ppm (J, Hz): 1.018 d [9H,
trum (CDCl3):
62.33 ppm. Found, %: N 7.15; P
(CH3)3C, JHP 17], 7.05 7.95 m (5H, C6H5), 5.29 d
8.27. C22H24FN2PPS. Calculated, %: N 7.03; P 8.03.
1
(1H, PH, JPH 454). 31P NMR spectrum (CDCl3):
P
p-Dimethylaminophenylphosphonothioic bis-
( -methylbenzylamide) (XIIIc) was synthesized as
described above for compound XIIIa. Yield 60%, mp
48.17 ppm, d (1JPH 454 Hz).
Phenylphosphonous bis( -methylbenzylamide)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004

522
KOLODYAZHNYI et al.
3
131 132 C (from toluene hexane, 5:1), [ ]D 14.81
spectrum (CDCl3), , ppm (J, Hz): 1.35 d (CH3, JHH
3
(c 1, CHCl3). 1H NMR spectrum (CDCl3), , ppm (J,
7.0), 1.42 d (CH3, JHH 7.0), 2.3 m (NH), 4.3 m (2H,
CH), 7.0 7.3 m (C6H5). 31P NMR spectrum (CDCl3):
84.88 ppm (1JPB 50 Hz). Found, %: N 10.11; P
7P.45. C24H33BN3P. Calculated, %: N 10.37; P 7.64.
3
Hz): 1.25 d (3H, CH3, JHH 7.5), 1.35 d (3H, CH3,
3JHH 7.5), 2.55 m (2H, CH), 2.99 s (6H, CH3N),
4.44 m (2H, NH), 6.53 7.84 m (9H, C6H5, C6H4). 31
P
NMR spectrum (CDCl3):
7.99. C24H30N3PS. Calculated S, %: 7.55.
64.42 ppm. Found S, %:
P
REFERENCES
tert-Butylphosphinic -methylbenzylamide
(XIVe). Formic acid, 0.01 mol, was added with stirring
and cooling to a solution of 0.01 mol of tert-butyl-
phosphonous bis( -methylbenzylamide) in toluene.
The mixture was allowed to warm up to room tempera-
ture and was left overnight. The precipitate was fil-
tered off, the filtrate was evaporated, and the residue
was distilled under reduced pressure. Yield 70%, bp
1. Kolodiazhnyi, O.I., Tetrahedron: Asymmetry, 1998,
vol. 9, no. 8, p. 1279.
2. Juaristi, E., Leun-Romo, J.-L., Reyes, A., and Es-
calante, J., Tetrahedron: Asymmetry, 1999, vol. 10,
no. 13, p. 2441.
3. Kolodiazhnyi, O.I., Grishkun, E.V., Golovatyi, O.R.,
and Ustenko, S.N., Phosphorus, Sulfur, Silicon, 1996,
vol. 109/110, p 485.
1
135 C (0.4 mm), [ ]D 91.5 (toluene). H NMR
spectrum (CDCl3), , ppm (J, Hz): 0.79 d [9H,
(CH3)3C, JPH 16.5], 1.45 d (3H, CH3, JHH 7), 4.2 q
(1H, CHN, JHH 7), 5.14 m (1H, NH), 7.8 m (5H,
4. Kolodiazhnyi, O.I. and Prynada, N., Tetrahedron Lett.,
2000, vol. 41, no. 41, p. 7997.
5. Imamoto, T., Pure Appl. Chem., 1993, vol. 65, no. 4,
1
C6H5), 6.33 d (1H, PH, JPH 494). 31P NMR spectrum
p. 655.
(CDCl3), P, ppm: 39.31 d (1JPH 495 Hz). Found P,
%: 13.39. C12H20NOP. Calculated P, %: 13.75.
6. Juge, S., Stephan, M., Laffitte, J.A., and Genet, J.P.,
Tetrahedron Lett., 1990, vol. 31, no. 44, p. 6357.
Methylphosphinic -methylbenzylamide (XIVd)
was synthesized as described above for compound
XIVe. Yield 78%, bp 120 C (0.05 mm), [ ]D 101.6
7. Juge, S. and Genet, J.P., Tetrahedron Lett., 1989,
vol. 30, no. 21, p. 2783.
1
8. Imamoto, T., Oshiki, T., Onazawa, T., Kusumoto, T.,
and Sato, K., J. Am. Chem. Soc., 1990, vol. 112,
no. 13, p. 5244.
(c 1, toluene). H NMR spectrum (CDCl3), , ppm (J,
Hz): 1.35 d (3H, CH3, JHH 7.3), 1.43 d (3H, CH3, JHH
7.0), 4.2 q (1H, CHN, JHH 7), 4.97 m (1H, NH),
1
7.05 7.95 m (5H, C6H5), 6.00 d (1H, PH, JPH 496).
9. Hamor, T.A., Jennings, W.B., Lovely, C.J., and
Reeves, K.A., J. Chem. Soc., Perkin Trans. 2, 1992,
no. 2, p. 843.
31P NMR spectrum (CDCl3), P, ppm: 20.54 d (1JPH
496 Hz). Found P, %: 16.35. C9H14NOP. Calculated
P, %: 16.91.
10. Skrzypczynski, Z. and Michalski, J., J. Org. Chem.,
1988, vol. 53, no. 19, p. 4549.
Phosphorous tris( -methylbenzylamide)borane
complex (XVf). a. Phosphorous tris( -methylben-
zylamide) (VIII). A solution of 0.01 mol of phospho-
rus(III) chloride in 10 ml of diethyl ether was added
dropwise under stirring to a solution of 0.033 mol of
( )-(S)- -methylbenzylamine and 0.033 mol of tri-
ethylamine in 15 ml of diethyl ether, cooled to 70 C.
The mixture was allowed to warm up to room tempera-
ture and was stirred for 0.5 h. The precipitate of tri-
ethylamine hydrochloride was filtered off, and the
filtrate was evaporated to obtain phosphorous tris( -
methylbenzylamide) (VIII) as a viscous liquid. Yield
90%. 31P NMR spectrum (CDCl3): P 104.8 ppm [4].
11. Drabowicz, J., Lyzwa, P., Omelanczuk, J., Pietrusi-
ewicz, K.M., and Mikolajczyk, M., Tetrahedron:
Asymmetry, 1999, vol. 10, no. 14, p. 2757.
12. Haynes, R.K., Freeman, R.N., Mitchel, C.R., and
Vonwiller, S.C., J. Org. Chem., 1994, vol. 59, no. 11,
p. 2919.
13. Kolodiazhnyi, O.I., Advances in Asymmetric Synthesis,
Hassner, A., Ed., Stamford: JAI, 1998, vol. 3, chap. 5,
p. 273.
14. Valentine, D., Jr., Asymmetric Synthesis, Morri-
son, J.D. and Scott, J.W., Eds., Orlando: Academic,
1984, vol. 4, p. 267.
b. Borane complex (XVe). Compound VIII was
quickly dissolved in THF, a solution of an equimolar
amount of borane in THF was added, and the mixture
was left overnight. The solvent was removed under
reduced pressure, and the residue was purified by
column chromatography on silica gel using hexane
15. Kolodyazhnyi, O.I. and Andrushko, N.V., Zh. Obshch.
Khim., 2001, vol. 71, no. 11, p. 1924.
16. Kolodyazhnyi, O.I. and Prinada, N.V., Zh. Obshch.
Khim., 2001, vol. 71, no. 4, p. 691.
17. Andrushko, N.V., Cand. Sci. (Chem.) Dissertation,
1
ethyl acetate (6:1) as eluent. Yield 50%. H NMR
Kiev, 2002.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 4 2004