Use of cis-dichloro[(S)-α-methylbenzylamine](ethylene)Pt(II) as a chiral derivatizing agent for the determination by 195Pt-NMR of the enantiomeric composition of unsaturated ethers or alcohols having a quaternary chiral carbon atom

Article abstract of DOI:10.1016/S0022-328X(99)00700-7

cis-Dichloro[(S)-α-methylbenzylamine](ethylene)platinum(II) is an efficient chiral derivatizing agent for the determination, by ¹⁹⁵Pt-NMR spectroscopy, of the enantiomeric composition of unsaturated ethers and alcohols having a quaternary chiral carbon atom.

Full text of DOI:10.1016/S0022-328X(99)00700-7

www.elsevier.nl/locate/jorganchem
Journal of Organometallic Chemistry 598 (2000) 174–178
Use of cis-dichloro[(S)-a-methylbenzylamine](ethylene)Pt(II) as a
195
chiral derivatizing agent for the determination by Pt-NMR of
the enantiomeric composition of unsaturated ethers or alcohols
having a quaternary chiral carbon atom
Gloria Uccello-Barretta, Raffaella Bernardini, Raffaello Lazzaroni, Piero Salvadori *
Dipartimento di Chimica e Chimica Industriale, Centro di Studio del CNR per le Macromolecole Stereordinate ed Otticamente Atti6e,
6ia Risorgimento 35, I-56126 Pisa, Italy
Received 22 September 1999; accepted 9 November 1999
Abstract
cis-Dichloro[(S)-a-methylbenzylamine](ethylene)platinum(II) is an efficient chiral derivatizing agent for the determination, by
195Pt-NMR spectroscopy, of the enantiomeric composition of unsaturated ethers and alcohols having a quaternary chiral carbon
atom. © 2000 Elsevier Science S.A. All rights reserved.
Keywords: Chiral derivatizing agent; NMR; Enantiomeric purity; Unsaturated ethers; Unsaturated alcohols
hols having a tertiary allylic chiral carbon atom
(CH2ꢀCHCHROR1, R1=H, Me). The corresponding
trans-complexes were employed for the analyses of
trisubstituted allenes (RR1CꢀCꢀCR2H) [2f–g].
1. Introduction
One of the most common and valuable direct meth-
ods for the determination of the enantiomeric composi-
tion involves the use of chiral derivatizing agents
(CDAs) [1] to convert enantiomeric pairs into
diastereoisomeric mixtures, which can be detected by
NMR.
The inherent simplicity of the method led to the
development of a variety of such effective chiral auxil-
iaries [1]. Among them, some organometallic CDAs
[1a,2] have the unique feature to involve the coordina-
tion of p-moieties of the analytes in the derivatization
reaction and platinum complexes, in particular, also
add the attractive opportunity of making possible the
detection of the diastereoisomeric mixtures by 195Pt-
NMR. Some years ago we had suggested the use of
cis-dichloro[(S)-a-methylbenzylamine](ethylene)Pt(II)
( 1 ) (see below), already reported as a resolving agent
for chiral unsaturated compounds [3], as CDA [2e] for
the 195Pt-NMR analyses of unsaturated ethers or alco-
In the present paper we will show that 1 is a CDA,
having general applicability also for the determination
of the enantiomeric composition of unsaturated ethers
* Corresponding author. Tel.: +39-50-918203; fax: +39-50-
918260.
E-mail address: psalva@dcci.unipi.it (P. Salvadori)
0022-328X/00/$ - see front matter © 2000 Elsevier Science S.A. All rights reserved.
PII: S0022-328X(99)00700-7

G. Uccello-Barretta et al. / Journal of Organometallic Chemistry 598 (2000) 174–178
175
Scheme 1.
and alcohols having a quaternary allylic or homoallylic
chiral carbon atom (see above, compounds 2).
In the 195Pt-NMR spectra of mixtures 3, obtained by
coordination of substrates 2, we always detected sepa-
rate absorptions (Table 1) for the diastereoisomers pro-
duced by each enantiomer. In the simplest case, as for
racemic allyl ether 2a, the 195Pt-NMR spectrum of the
diastereoisomeric mixture showed only two well re-
2. Results and discussion
The use of complex 1 as chiral derivatizing agent is
especially practical as the derivatization process simply
involves the exchange of its coordinated ethylene by the
enantiomeric mixtures to be analyzed, to produce com-
plexes 3 (Scheme 1). This reaction can be suitably
carried out by mixing the two components, 1 and 2, in
the deuterated solvent (CDCl3) (1/2=1:0.8–0.6). As
the formation of the diastereoisomeric mixtures is
quantitative and fast and can be performed directly in
the NMR tube, the 195Pt-NMR spectroscopy consti-
tutes an ease way to their analysis. In fact, the spectral
characteristics of the nucleus involved (195Pt, I=1/2,
33% natural abundance) make possible their detection
in short instrumental times (about 5–10 min) by using
standard pulse sequences, for solutions containing
about 100 mg of substances in 0.5 ml of deuterated
solvent and the analysis of the diastereoisomers is not
complicated by splittings due to J coupling (at least in
this kind of complexes). Finally, the same equilibrium
reaction (Scheme 1), which is employed to obtain the
diastereoisomeric mixture, can be used to recover both
the CDA and the complexed unsaturated substrate, by
treating with an excess of ethylene. The coordination of
the two prochiral faces of the double bond of each
enantiomer of the unsaturated analyte produces two
diastereoisomers whose ratio depends on its structure
(Scheme 1). Therefore, complexes 3 are constituted by a
maximum number of four diastereoisomers in solution.
As, in principle, each of them can originate a single
195Pt resonance, the determination of the enantiomeric
composition can be simply performed by comparing the
areas of the signals originated by each enantiomer.
Table 1
195Pt-NMR spectrum (64.3 MHz, CDCl3, 25°C, Na2PtCl6 external
standard) of diastereoisomeric complexes containing compounds 2
Complex
l (ppm)
3a
3b
3c
3d
3e
3f
−2715, −2693
−2742, −2713, −2653, −2636
−2714, −2700, −2695, −2678
−2692, −2670
−2731, −2724, −2710, −2701
−2727, −2708, −2700
−2726, −2722
3g
Fig. 1. 195Pt-NMR spectrum (64.3 MHz, CDCl3, 25°C, Na2PtCl6
external standard) of complex cis-dichloro[(S)-a-methylbenzyl-
amine](2a)Pt(II): (a) (R)(S)-2a; (b) (S)-2a; (c) (R)-2a.

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isomers are still differentiated. The coordination of the
ether 2g, analogous of 2f, proceeds with total stereo-
selectivity originating only two signals.
However, the important fact is that for all cases, the
relative amounts of the two enantiomers can be mea-
sured or directly comparing the areas of the two signals
(2a, 2d, 2g) or the sum of the areas of the two signals
originated by each enantiomer (2b, 2c, 2e, 2f).
3. Conclusions
Fig. 2. 195Pt-NMR spectrum (64.3 MHz, CDCl3, 25°C, Na2PtCl6
external standard) of complex cis-dichloro[(S)-a-methylbenzyl-
amine][(R)(S)-2b]Pt(II).
In conclusion, complex 1 represents an efficient CDA
for NMR spectroscopy having a widespread applicabil-
ity to the analyses of unsaturated ethers or alcohols
containing an allylic or homoallylic quaternary chiral
carbon atom. To this regard we wish to focus that,
overall in the case of ethers, no alternative general
direct methods of analyses have been reported. Taking
into account that efficiency of CDA 1 in the enan-
tiomeric purity determination of analogous allylic
ethers and alcohols having a tertiary chiral carbon
atom had been already proved [2e], it affords one of the
most general direct methods for the analyses of this
kind of compounds. Previous investigations [4] on com-
plexes containing a primary amine cis to a chiral allyl
ether demonstrated the occurrence of a hydrogen bond
interaction NH···O, which imposes different proximity
constraints between the platinum nucleus and the
groups bound to the chiral carbon atom of the coordi-
nated unsaturated ether, as well as between it and the
amine ligand. Reasonably, these interactions are re-
sponsible for the different deshielding effects on the
metal nucleus, thus leading to the possibility of differ-
entiating between the 195Pt absorptions of the
diastereoisomeric species.
solved resonances at −2715 and −2693 ppm, having
equal intensities (Fig. 1a). The comparison of this spec-
trum with those of the complexes prepared from the
single enantiomers (Fig. 1b, c) allowed us to assign the
two resonances to the complexed (S)- and (R)-enan-
tiomers, respectively.
The mixture arising from the complexation of
racemic 2b gives rise to two pairs of sharp signals
having different intensities, each due to a single enan-
tiomer (Fig. 2). Therefore, in the case of 2b, having two
alkyl substituents at the quaternary chiral center, each
enantiomer originates different amounts of two
diastereoisomers which are all detected: probably the
coordination of the prochiral face bringing the sterically
t
hindered Bu group in proximity of the platinum is less
favorable than the coordination of the other prochiral
face bringing the Me group towards the metal. It is
noted that in the above case of 2a, leading a phenyl and
an alkyl group, where only two signals were detected,
the complexation of each enantiomer proceeds with
total diastereoselectivity or 195Pt-NMR cannot distin-
guish the complexation of the two prochiral faces of
each enantiomer.
4. Experimental
For allyl alcohol 2c, structurally analogous to 2a,
four absorptions are observed (Table 1) corresponding
to the complexation of the two enantiofaces of the two
enantiomers, whereas in the case of 2d, having an
isopropyl group in place of the methyl one, only two
signals are observed.
4.1. General
195Pt-NMR spectra were recorded in CDCl3 at 64.3
MHz. All 195Pt-NMR chemical shifts are referenced to
Na2PtCl6 as external standard and the 195Pt resonance
Also homoallylic systems are discriminated in the
195Pt-NMR spectra of the corresponding complexes
(Table 1), however the chemical shift differences are
lower than they are for allylic compounds, probably
due to the minor rigidity of the coordinated unsatu-
rated substrate in the former, relatively to the latter
ones, as observed for the structurally analogous 2c and
2e. The introduction of a more hindered isopropyl
group in 2f diminishes the chemical shift differences of
the prevailing stereoisomers, which originate two par-
tially superimposed resonances, whereas the two minor
of
cis-dichloro[(S)-a-methylbenzylamine](ethylene)-
Pt(II) (1) is at lower frequencies (−2780 ppm) than the
absorptions due to complexes containing substrates 2.
Standard pulse sequences have been employed for 195Pt-
NMR measurements.
4.2. Materials
Carbonyl compounds were purchased from Fluka
A.G. Co., Buchs. Tetrahydrofuran (THF) was distilled
from LiAlH4 prior to use. Grignard reagents were

G. Uccello-Barretta et al. / Journal of Organometallic Chemistry 598 (2000) 174–178
177
prepared in THF and standardized by titration meth-
ods. Alcohols were prepared by addition of Grignard
reagents to carbonyl compounds [5]. Racemic 2c was
resolved by crystallization of brucine salts of its hydro-
genphtalate [6]. The methyl ethers were prepared from
the corresponding alcohols first with sodium hydride
and then with methyl iodide [7]. cis-Dichloro[(S)-a-
methylbenzylamine](ethylene)platinum(II) (1) has been
prepared according to literature procedure [8].
(1H, bs, OH), 1.99 (1H, dq, J=6.9 Hz, CH), 2.52 (1H,
dd, J=13.8 Hz, J=8.9 Hz, CH2), 2.79 (1H, ddt,
J=13.8 Hz, J=5.5 Hz, J=1.2 Hz, CH2), 5.05 (1H,
dd, J=9.9 Hz, J=1.2 Hz, CꢀCH2), 5.11 (1H, ddt,
J=16.9 Hz, J=1.2 Hz, J=1.2 Hz, CꢀCH2), 5.46 (1H,
m, CHꢀCH2), 7.16–7.45 (5H, m, Ph); 13C-NMR l=
16.8, 17.5, 37.9, 43.9, 119.4, 126.0, 126.3, 127.7, 134.0,
140.3. Anal. Calc. for C13H18O: C, 82.06; H, 9.53.
Found: C, 82.03; H, 9.50%.
1
1
2a: 60% yield; b.p. 45°C (1 mmHg); H-NMR l=
2g: 73% yield; b.p. 70–71°C (1 mmHg); H-NMR
1.59 (3H, s, CH3), 3.18 (3H, s, OCH3), 5.23 (1H, dd,
J=17.4 Hz, J=1.2 Hz, CꢀCH2), 5.25(1H, dd, J=10.6
Hz, J=1.2 Hz, CꢀCH2), 6.01 (1H, dd, J=17.4 Hz,
J=10.6 Hz, CHꢀCH2), 7.19–7.44 (5H, m, Ph); 13C-
NMR l=23.9, 50.7, 114.4, 126.2, 127.0, 128.1, 142.7,
144.5. Anal. Calc. for C11H14O: C, 81.44; H, 8.70.
Found: C, 81.41; H, 8.66%.
l=0.71 (3H, d, J=6.7 Hz, CH3), 0.74 (3H, d, J=6.7
Hz, CH3), 2.10 (1H, dq, J=6.7 Hz, CH), 2.74 (1H, ddt,
J=15.6 Hz, J=5.4 Hz, J=1.8 Hz, CH2), 2.89 (1H,
ddt, J=15.6 Hz, J=8.3 Hz, J=1.1 Hz, CH2), 3.17
(3H, s, OCH3), 5.12 (1H, ddt, J=10.1 Hz, J=1.4 Hz,
J=1.1 Hz, CꢀCH2), 5.18 (1H, ddt, J=17.1 Hz, J=1.8
Hz, J=1.4 Hz, CꢀCH2), 5.89 (1H, m, CHꢀCH2), 7.18–
7.42 (5H, m, Ph); 13C-NMR l=16.7, 17.8, 34.8, 36.5,
50.3, 117.4, 126.0, 126.5, 127.3, 127.9, 134.0, 140.4.
Anal. Calc. for C14H20O: C, 82.30; H, 9.87. Found: C,
82.33; H, 9.83%.
2b: 57% yield; b.p. 120–121°C; 1H-NMR l=0.91
(9H, s, tBu), 1.18 (3H, s, CH3), 3.12 (3H, s, OCH3), 5.06
(1H, dd, J=17.3 Hz, J=1.6 Hz, CꢀCH2), 5.23 (1H,
dd, J=10.7 Hz, J=1.6 Hz, CꢀCH2), 5.81 (1H, dd,
J=17.3 Hz, J=10.7 Hz, CHꢀCH2). Anal. Calc. for
C9H18O: C, 76.00; H, 12.75. Found: C, 76.08; H,
12.73%.
4.3. General procedure
2c: 63% yield; b.p. 72°C (1 mmHg) [lit. [5a] b.p.
73–74°C (1 mmHg)]; H-NMR l=1.64 (3H, s, CH3),
4.3.1. Enantiomeric composition determination
The complex 1 (50 mg) is suspended in 0.5 ml of
CDCl3 into the NMR tube and added by 2 (molar ratio
1/2=1:0.8–0.6). The sample is then analyzed by 195Pt-
NMR.
1
2.29 (1H, bs, OH), 5.13 (1H, dd, J=10.5 Hz, J=1.1
Hz, CꢀCH2), 5.28 (1H, dd, J=17.1 Hz, J=1.1 Hz,
CꢀCH2), 6.16 (1H, dd, J=17.1 Hz, J=10.5 Hz,
CHꢀCH2), 7.20–7.51 (5H, m, Ph); 13C-NMR l=29.3,
112.3, 125.1, 127.0, 128.2, 144.9, 146.4. Anal. Calc. for
C10H12O: C, 81.04; H, 8.16. Found: C, 81.08; H, 8.18%.
2d: 94% yield; b.p. 122°C (17 mmHg) [lit. [5b] b.p.
119–120°C (18 mmHg)]; 1H-NMR l=0.77 (3H, d,
J=6.9 Hz, CH3), 0.89 (3H, d, J=6.9 Hz, CH3), 1.77
(1H, bs, OH), 2.17 (1H, dq, J=6.9 Hz, CH), 5.17 (1H,
dd, J=10.7 Hz, J=1.2 Hz, CꢀCH2), 5.31 (1H, dd,
J=17.2 Hz, J=1.2 Hz, CꢀCH2), 6.28 (1H, dd, J=
17.2 Hz, J=10.7 Hz, CHꢀCH2), 7.17–7.49 (5H, m,
Ph); 13C-NMR l=16.7, 17.1, 37.3, 112.7, 125.5, 126.6,
128.0, 143.2, 145.7. Anal. Calc. for C12H16O: C, 81.77;
H, 9.15. Found: C, 81.75; H, 9.19%.
4.3.2. Preparation and purification of cis-dichloro-
[(S)-h-methylbenzylamine](2)platinum(II) (3)
On treatment of 1 (50–210 mg) in CH2Cl2 solution (5
ml) with 2 (molar ratio 1/2=1:1), the ethylene was
immediately displaced. Removal of the solvent under
vacuum afforded 3 quantitatively as a pale yellow
microcrystalline solid. The crude product was purified
(60–70% yield) by crystallization at room temperature
from CHCl3–pentane (1:2). Elemental analyses and
melting points of the crystallized complexes 3 are as
follows.
3a: m.p. 145–147°C. Anal. Calc. for C19H25Cl2NOPt:
C, 41.54; H, 4.59; N, 2.55. Found: C, 41.27; H, 4.36; N,
2.87%.
2e: 96% yield; b.p. 100°C (17 mmHg) [lit. [5c] 98–
1
112°C (15 mmHg)]; H-NMR l=1.53 (3H, s, CH3),
2.18 (1H, bs, OH), 2.48 (1H, ddt, J=13.8 Hz, J=8.3
Hz, J=1.0 Hz, CH2), 2.67 (1H, ddt, J=13.8 Hz,
J=6.4 Hz, J=1.0 Hz, CH2), 5.09 (1H, ddt, J=10.3
Hz, J=2.3 Hz, J=1.0 Hz, CꢀCH2), 5.11 (1H, ddt,
J=16.8 Hz, J=2.3 Hz, J=1.0 Hz, CꢀCH2), 5.61 (1H,
m, CHꢀCH2), 7.15–7.50 (5H, m, Ph); 13C-NMR l=
29.9, 48.5, 119.3, 124.7, 126.6, 128.1, 133.7, 147.7. Anal.
Calc. for C11H14O: C, 81.44; H, 8.70. Found: C, 81.40;
H, 8.73%.
3b: m.p. 107–109°C. Anal. Calc. for C17H29Cl2NOPt:
C, 38.57; H, 5.52; N, 2.65. Found: C, 38.45; H, 5.68; N,
2.47%.
3c: m.p. 167–169°C. Anal. Calc. for C18H23Cl2NOPt:
C, 40.38; H, 4.33; N, 2.62. Found: C, 39.77; H, 4.63; N,
2.36%.
3d: m.p. 145–146°C. Anal. Calc. for C20H27Cl2NOPt:
C, 42.64; H, 4.83; N, 2.49. Found: C, 43.49; H, 5.01; N,
2.31%.
2f: 94% yield; b.p. 120°C (17 mmHg) [lit. [5d] b.p.
118–124°C (17 mmHg)]; 1H-NMR l=0.75 (3H, d,
J=6.9 Hz, CH3), 0.93 (3H, d, J=6.9 Hz, CH3), 1.92
3e: m.p. 103–105°C. Anal. Calc. for C19H25Cl2NOPt:
C, 41.54; H, 4.59; N, 2.55. Found: C, 40.65; H, 4.69; N,
2.14%.

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G. Uccello-Barretta et al. / Journal of Organometallic Chemistry 598 (2000) 174–178
Buriak, J.A. Osborn, J. Chem. Soc. Chem. Commun. (1995) 689.
3f: m.p. 99–101°C. Anal. Calc. for C21H29Cl2NOPt:
(e) P. Salvadori, G. Uccello-Barretta, S. Bertozzi, R. Settambolo,
R. Lazzaroni, J. Org. Chem. 53 (1988) 5768. (f) P. Salvadori, G.
Uccello-Barretta, R. Lazzaroni, A.M. Caporusso, J. Chem. Soc.
Chem. Commun. (1990) 1121. (g) G. Uccello-Barretta, F. Bal-
zano, P Salvadori, R. Lazzaroni, A.M. Caporusso, R. Menicagli,
Enantiomer 1 (1996) 365. (h) V.V. Dunina, L.G. Kuz’mina, M.
Yu. Kazakova, Yu. K. Grishin, Yu. A. Veits, E.I. Kazakova,
Tetrahedron Asymm. 8 (1997) 2537. (i) B. Staubach, J. Buddrus,
Angew. Chem. Int. Ed. Engl. 35 (1996) 1344. (j) J. Albert, J.
Granell, G. Muller, D. Sainz, M. Font-Bardia, X. Solans, Tetra-
hedron Asymm. 6 (1995) 325. (k) J. Klein, S. Neels, R. Borsdorf,
J. Chem. Soc. Perkin Trans 2 (1994) 2523. (l) D.B. Grotjahn, C.
Joubran, Tetrahedron Asymm. 6 (1995) 745.
C, 43.68; H, 5.06; N, 2.43. Found: C, 43.54; H, 5.14; N,
1.92%.
3g: m.p. 117–119°C. Anal. Calc. for C22H31Cl2NOPt:
C, 44.67; H, 5.28; N, 2.37. Found: C, 44.32; H, 5.41; N,
2.48%.
Acknowledgements
This work has been supported partially by CNR and
MURST, Roma, Italy.
[3] (a) R. Lazzaroni, P. Salvadori, P. Pino, Tetrahedron Lett. (1968)
2507. (b) R. Lazzaroni, G. Uccello-Barretta, D. Pini, S. Pucci, P.
Salvadori, J. Chem. Res. (S) (1983) 286.
[4] G. Uccello-Barretta, R. Lazzaroni, C. Bertucci, P. Salvadori,
Organometallics 6 (1987) 550.
References
[5] (a) C.S. Marvel, G.R. Woolford, J. Org. Chem. 23 (1958) 1658.
(b) J. Cologne, J.-C. Brunie, Bull. Soc. Chim. Fr. 1 (1963) 42. (c)
V.R. Skvarchenko, W.-L. Ling, N.V. Sedykh, R. Ya. Levina, Zh.
Obshch. Khim. 32 (1962) 217. (d) K. Maruyama, K. Murakami,
Bull. Chem. Soc. Jpn. 41 (1968) 1401.
[6] R.J.D. Evans, S.R. Landor, J. Chem. Soc. (1965) 2553.
[7] C.A. Brown, D. Barton, Synthesis (1974) 434.
[8] A. Panunzi, G. Paiaro, J. Am. Chem. Soc. 88 (1966) 4843.
[1] (a) D. Parker, Chem. Rev. 91 (1991) 1441. (b) S. Yamaguchi, in:
J.D. Morrison (Ed.), Asymmetric Synthesis, vol. 1, Academic,
New York, 1983, p. 125–149. (c) R. Hulst, R.M. Kellogg, B.L.
Feringa, Recl. Trav. Chim. Pays-Bas 114 (1995) 115.
[2] (a) D. Parker, R.J. Taylor, Tetrahedron 44 (1988) 2241. (b) D.
Parker, R.J. Taylor, J. Chem. Soc. Chem. Commun. (1987) 1781.
(c) S.Y.M. Chooi, P. Leung, C.C. Lim, K.F. Mok, G.H. Quek,
K.Y. Sim, M.K. Tan, Tetrahedron Asymm. 3 (1992) 529. (d) J.M.
.