Asymmetric synthesis of chiral N-(1-methylbenzyl)aminophosphines

Article abstract of DOI:10.1016/S0957-4166(02)00750-4

The reactions of chlorophosphines 1 with (S)- or (R)-1-methylbenzylamines 2 proceed stereoselectively to give N-(1-methylbenzyl)aminophosphines 3, which were isolated as crystalline borane complexes with 100% diastereomeric purity. The absolute configuration of the new chiral compounds was established by X-ray analysis and chemical extrapolation.

Full text of DOI:10.1016/S0957-4166(02)00750-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 181–183
Asymmetric synthesis of chiral
N-(1-methylbenzyl)aminophosphines
Oleg I. Kolodiazhnyi,a,* Evgenyi V. Gryshkun,a Natalia V. Andrushko,a,† Matthias Freytag,b Peter
G. Jonesb and Reinhard Schmutzlerb
aInstitute of Bioorganic Chemistry, National Academy of Sciences of Ukraine, Murmanskaia Street, 1, Kiev, Ukraine
bInstitut fu¨r Anorganische und Analytische Chemie, Technische Universita¨t, Hagenring 30, 38106 Braunschweig, Germany
Received 3 November 2002; accepted 12 November 2002
Abstract—The reactions of chlorophosphines 1 with (S)- or (R)-1-methylbenzylamines 2 proceed stereoselectively to give
N-(1-methylbenzyl)aminophosphines 3, which were isolated as crystalline borane complexes with 100% diastereomeric purity. The
absolute configuration of the new chiral compounds was established by X-ray analysis and chemical extrapolation. © 2003
Elsevier Science Ltd. All rights reserved.
Chiral trivalent organophosphorus compounds having
a sterogenic phosphorus centre are important subjects
of investigation due to the widespread use of these
compounds as ligands for transition metal catalysis.
The numerous patented chiral phosphines and
aminophosphines are proof of the interest in such cata-
lytic reactions from the industrial world.2,3
The stereoselectivity of the reaction between
chlorophosphines 1 and N-(1-methylbenzyl)amine 2 in
the presence of tertiary bases depends strongly on the
reaction conditions and the nature of the base, solvent,
temperature and ratio of starting reagents all affect the
stereochemical outcome (Scheme 1). Under certain con-
ditions this reaction proceeds with sufficient stereoselec-
tivity to give diastereomerically enriched amino-
phosphines 3 (Scheme 1, entries 1 and 12). The
aminophosphines 3 are colorless liquids that can be
distilled under vacuum. The yields of aminophosphines
after distillation are 75–80%.
A few years ago, we reported a method for the asym-
metric synthesis of phosphinic and phosphinous acid
esters using the reaction of chiral alcohols with racemic
nonsymmetrically substituted chlorophosphines in the
presence of tertiary bases.4 Proceeding with these stud-
ies, we have examined the reaction of the chlorophos-
The subsequent treatment of aminophosphines 3a with
borane in tetrahydrofuran (THF) leads to the forma-
tion of the stable crystalline adduct 4 in essentially
quantitative yield. The complexes 4 were then purified
phines
1
with the (S)- or (R)-enantiomers of
N-(1-methylbenzyl)amine 2, resulting in the formation
of diastereomerically enriched N-(1-methylbenzyl)-
aminophosphines 3 which, upon treatment with borane,
provide the enantiomerically pure aminophosphines 3
(Scheme 1).
1
by crystallization from hexane. H, 13C and 31P NMR
analyses of the borane complex 4a indicated the forma-
tion of only one diastereomer.7 The BH3 group of the
phosphine–borane complex 4a was removed on treat-
ment with a large excess of diethylamine to furnish the
initial aminophosphine 3a in 100% stereochemical
purity.8 This reaction has been proven to proceed in a
stereospecific manner with retention of configura-
tion.9,10
The diastereoselective reaction of chiral amines with
phosphorus(III) chlorides has not been described previ-
ously, although the reaction of the amines 2 with
phosphorus(V) chlorides has literature precedence.5,6
The reaction permits facile access to enantiomerically
pure aminophosphines 3, which are potential starting
materials for the synthesis of numerous chiral
organophosphorus compounds (Scheme 2).
* Corresponding author. Fax: 38(044)573-2552; e-mail: oikol123@
bpci.kiev.ua
† See Ref. 1
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00750-4

182
O. I. Kolodiazhnyi et al. / Tetrahedron: Asymmetry 14 (2003) 181–183
Scheme 1. The asymmetric synthesis of aminophosphines 3.
Scheme 2. R*=CH(Me)Ph.
Thus, the (Rp,S)-aminophosphine 3a was allowed to
react with methanol to give the methyl (S)-(−)-tert-
butylphenylphosphinate 5. The hydrolysis of (Rp,S)-N-
(1-methylbenzyl)amino-t-butylphenylphosphine 3a in
aqueous dioxane (80°C, 12 h) or acidolysis of 3a with
formic acid in toluene (15–30 min, 0°C) resulted in the
formation of optically active (S)-(−)-t-butylphenylphos-
phine oxide 5.11 The specific rotation and other physical
data for compound 5, synthesized by us, and of (S)-(−)-
t-butylphenylphosphine oxide, described in the litera-
ture, are identical.12a–c
Figure 1.
diastereomer mixture 3a using the same conditions
provided a diastereomeric mixture of (Sp,S)- and
(Rp,S)-aminophosphine oxides 7a.
The diastereomers 7 were separated by flash-chro-
matography. The products (Sp,S)- and (Rp,S)-7 were
crystalline13,14 and a single crystal X-ray structural
analysis established the absolute configuration of
(Sp,S)-7 (Fig. 1).15 The thionation of the compounds 3a
gave the pure (Sp,S)-diastereomer of the phosphine
sulfide 8, which was isolated by crystallization from
The oxidation of aminophosphine (Rp,S)-3a by hydro-
gen peroxide in dioxane afforded only the (Sp,S)-
diastereomer of aminophosphine oxide 7a in a very
good yield. The oxidation of the (Rp,S)+(Sp,S)-
hexane as
a
colorless stable solid in ꢀ100%
diastereoisomeric purity.16,17

O. I. Kolodiazhnyi et al. / Tetrahedron: Asymmetry 14 (2003) 181–183
183
In summary, we have developed an accessible method
for the preparation of chiral aminophosphines, which
can be used as starting compounds for the asymmetric
synthesis of organophosphorus compounds or as chiral
ligands. We are currently studying the borane com-
plexes 4 as chiral catalysts for the asymmetric reduction
of CꢀO and CꢀN groups and the results of these studies
will be reported in due course.
11. Data for (S)-(−)-6: Yield 80%, [h]D −44.6 (c 1, toluene),
1
{lit. [h]D −40.45 (c 1.78, MeOH)12}. H NMR (l, ppm; J,
Hz; CDCl3) 1.018, d [JHH 17, (CH3)3C]; 7.05–7.95, m
(C6H5); 5.29, d (1JPH 454, PH). 31P NMR (l, ppm, J, Hz;
CDCl3) 48.17, d (1JPH 454 Hz).
12. (a) Skrzypczynski, Z.; Michalski, J. J. Org. Chem. 1988,
53, 4549–4551; (b) Drabowicz, J.; Lyzwa, P.; Ome-
lanczuk, J.; Pietrusiewicz, K. M.; Mikolajczyk, M. Tetra-
hedron: Asymmetry 1999, 10, 2757–2763; (c) Haynes, R.
K.; Freeman, R. N.; Mitchel, C. R.; Vonwiller, S. C. J.
Org. Chem. 1994, 59, 2919–2921.
Acknowledgements
13. Data for (Sp,S)-7: Yield 80% (summary). [h]D −82.5 (c 1,
ethanol), mp 171–172°C (ethyl acetate). 1H NMR (l,
ppm; J, Hz; CDCl3) 1.01, d [JHH 14.8, (CH3)3C]; 1.33, d
(JHP 7.0, CH3); 2.80, br (NH); 4.44, br (JHH 8, CH);
7.19–7.4, m; 7.87, m (C6H5). 31P NMR (l, ppm; CDCl3):
lP 41.32. The absolute configuration of (Sp,S)-7 was
determined by X-ray analysis (see Fig. 1).
Financial support for this work from the Deutsche
Forschungsgemeinschaft (DFG) and the State Founda-
tion of Basic Researches of Ukraine (Project 03.07/
00047) is gratefully acknowledged.
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6
H3)3C]; 25.57,
d (3JCP 5.20, CH3CHN); 30.69, d [1JCP 43.40, (CH3)3C
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6
]
;
52.47, d (2JCP 2.01, CHN); 126.10, s; 126.94, s; 127.58, d,
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d, JCP 9.40 (C6H5).
−0.05(8). Hydrogen atoms included using
a rigid
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(methyls) or a riding (others) model. Final wR2 0.0720,
with R1 0.0375, for 394 parameters and three restraints; S
1.013; max. Dz 0.223 e nm−3. Crystallographic data
(excluding the structure factors) for the structure have
been deposited at the Cambridge Crystallographic Data
Centre, 12 Union Rd., GB-Cambridge CB2 1EZ, as
supplementary publication no. CCDC 195666. Copies
may be obtained free of charge on application to the
Director (Telefax: Int. +12 23 33 60 33;
http:¯¯www.deposit@ccdc.cam.ac.uk).
1
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7.0, CH3C]; 1.60, m (NH); 1.45, d [3JHH 14.0, (CH3)3C];
3.54, m (CHN); 7.10–7.33, m (C6H5). 31P NMR (l, ppm,
CDCl3) 49.00.
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