An approach to the synthesis of platinum complexes containing chiral monodentate phosphines with simultaneous regeneration of the resolving agent

Article abstract of DOI:10.1021/om970176i

Elution of compounds [PdCl{3-ClC₆H₃-CH=NCH(Me)Ph} {trans-2-PPh₂(CyOH)}] 5a and [PdX{C₆H₄CH(Me)NH₂}{Ph₂PCH(OMe)Ph}] 6b, containing the racemic phosphines as ligands, through a SiO

Full text of DOI:10.1021/om970176i

Organometallics 1997, 16, 3561-3564
3561
An Ap p r oa ch to th e Syn th esis of P la tin u m Com p lexes
Con ta in in g Ch ir a l Mon od en ta te P h osp h in es w ith
Sim u lta n eou s Regen er a tion of th e Resolvin g Agen t
J oan Albert,† J aume Granell,*,† J orge M´ınguez,† Guillermo Muller,†
Daniel Sainz,† and Pedro Valerga‡
Departament de Qu´ımica Inorga`nica, Universitat de Barcelona, Diagonal 647,
08028 Barcelona, Spain, and Departamento de Ciencia de los Materiales,
Ingenierı´a Metalu´rgica y Quı´mica Inorga´nica, Facultad de Ciencias,
Universidad de Ca´diz, Apdo. 40, 11510 Puerto Real, Ca´diz, Spain
Received March 3, 1997X
Summary: Elution of compounds [PdCl{3-ClC6H3-
CHdNCH(Me)Ph}{trans-2-PPh2(CyOH)}] 5a and
[PdX{C6H4CH(Me)NH2}{Ph2PCH(OMe)Ph}] 6b, con-
taining the racemic phosphines as ligands, through a
SiO2 column allows the separation of the two diastereo-
isomers. Optically active coordination complexes trans-
[PtCl2{Ph2PCH(OMe)Ph}2] and trans-[PtCl2{Ph2PCH-
(OMe)Ph}(PPh3)], have been obtained by ligand transfer
reactions between 6b and PtCl2 or trans-[PtCl(µ-Cl)-
(PPh3)]2, respectively. The dinuclear cyclopalladated
resolving agent can be separated from the platinum
compounds and used in a new resolution process.
very recently a sequence of reactions has been described
that allows the regeneration of the resolving agent.4e
As a rule, the separation of the diastereoisomers
containing cyclopalladated units is based on the solubil-
ity difference. In only a few cases the separation has
been accomplished by column chromatography. Yoneda
et al.5 have described the resolution of palladium
complexes containing a Pd-C*(sp3) bond by column
chromatography (150 cm high), and recently Dunina et
al.4d have described the purification of two diastereo-
isomers containing tert-butylmethylphenylphosphine by
using several flash columns.
The resolution of racemic phosphines is an area of
considerable current interest because chiral phosphines1
are extensively used in a wide range of enantioselective
transition-metal catalytic processes.2 Cyclopalladated
complexes have been successfully used for the resolution
of bidentate P-E ligands, (E ) P, N, As, S...)3 and
monodentate phosphines,4 through recrystallization or
column chromatography purification of the diastereo-
meric transition metal complexes [PdX(C-N)L] or [Pd-
(C-N)L2]+ and subsequent decoordination of the phos-
phine. Unfortunately, nearly all the examples described
so far for the separation of phosphine ligands using
these methods result in palladacycle degradation. Only
In this paper we describe the resolution of function-
alized monodentate phosphines using a single column
chromatography of the corresponding diastereomeric
cyclopalladated derivatives [PdCl(C-N)L] and the syn-
thesis of optically active platinum coordination com-
pounds with simultaneous regeneration of the resolution
agent.
Resu lts a n d Discu ssion
The homochiral complexes (R)-[PdX{3-ClC6H3CHd
NCH(Me)Ph}]2 (X ) Cl or Br) and (R)-[PdX{C6H4CH-
(Me)NH2}]2 (X ) Cl or Br) were obtained from the
corresponding optically active imine or amine, by reac-
tion with palladium acetate and subsequent treatment
with LiX of the acetato dimer compounds.6 Reaction of
dimers 2 and 3 with the monodentate phosphines L
afforded the mononuclear derivatives [PdX(C-N)L], L )
PPh3, trans-2-PPh2(CyOH) or Ph2PCH(OMe)Ph (see
Scheme 1).7
† Universitat de Barcelona.
‡ Universidad de Ca´diz.
X Abstract published in Advance ACS Abstracts, J uly 1, 1997.
(1) For recent references on chiral phosphines, see: (a) Pietrusiewicz,
K. M.; Zablocka, M. Chem. Rev. 1994, 94, 1375. (b) Burk, M. J .; Feaster,
J . E.; Nugent, W. A.; Harlow R. L. J . Am. Chem. Soc. 1993, 115, 10125.
(c) Trost, B. M.; Van Vranken, D. L.; Bingel, C. J . J . Am. Chem. Soc.
1992, 114, 9327.
(2) For recent reviews on asymmetric catalysis, see: (a) Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH Publishers: Weinheim,
1993. (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; J ohn
Wiley and Sons: New York, 1994.
All the new compounds obtained were characterized
1
by elemental analysis, IR spectra, and H and 31P NMR
spectra. In some cases, COSY experiments were un-
dertaken to complete the NMR studies. The crystal
structure of 4a has been determined (Figure 1) and
crystallographic data are listed in Table 1.
(3) For recent references in this subject see: (a) Alcock, N. W.;
Brown, J . M.; Hulmes, D. I. Tetrahedron: Asymmetry 1993, 4, 743.
(b) Choi, S. Y. M.; Siah, S.; Leung, P; Mok, K. F. Inorg. Chem. 1993,
32, 4812. (c) Gabbitas, N.; Salem, G.; Sterns, M.; Willis, A. C. J . Chem.
Soc., Dalton Trans. 1993, 3271. (d) Aw, B.; Leung, P. Tetrahedron:
Asymmetry 1994, 5, 1167. (e) Ramsden, J . A.; Brown, J . M.; Hurst-
house, M. B.; Karaulov, A. I. Tetrahedron: Asymmetry 1994, 5, 2033.
(f) Doyle, R. J .; Salem, G.; Willis, A. C. J . Chem. Soc., Dalton Trans.
1995, 1867. (g) Leitch, J .; Salem, G.; Hockless, D. C. R. J . Chem. Soc.,
Dalton Trans. 1995, 649.
The crystal structure consists of discrete molecules
separated by van der Waals distances. Bond distances
(4) (a) Tani, K. J .; Brown, L. D.; Ahmed, J .; Ibers, J . A.; Yokota, M.;
Nakamura, A.; Otsuka, S. J . J . Am. Chem. Soc. 1977, 99, 7876. (b)
Gladiali, S.; Dore, A.; Fabbri, D.; De Lucchi, O.; Manassero, M.
Tetrahedron: Asymmetry 1994, 5, 511. (c) Pabel, M.; Willis, A. C.; Wild,
S. B. Angew. Chem., Int. Ed. Engl. 1994, 33, 1835. (d) Pabel, M.; Willis,
A. C.; Wild, S. B. Tetrahedron: Asymmetry 1995, 6, 2369. (e) Dunina,
V. V.; Golovan, F. B.; Gulyukina, N. S.; Buyevich, A. V. Tetrahedron:
Asymmetry 1995, 6, 2731. (f) Dunina, V. V.; Golovan, F. B. Tetrahe-
dron: Asymmetry 1995, 6, 2747. (g) Pabel, M.; Willis, A. C.; Wild, S.
B. Inorg. Chem. 1996, 35, 1244.
(5) Yoneda, A.; Hakushi, T.; Newkome, G. R.; Fronczek, F. R.
Organometallics 1994, 4912.
(6) Cyclopalladated dinuclear compound 3b has been previously
prepared by reaction of [PdCl2{C6H5CH(Me)NH2}2] with AgClO4:
Vicente, J .; Saura-Llamas, I.; J ones, P. G. J . Chem. Soc., Dalton Trans.
1993, 3619.
(7) For the synthesis of phosphines trans-PPh2(2-OHC6H10) and Ph2-
PCH(OMe)Ph, see Muller, G.; Sainz, D. J . Organomet. Chem. 1995,
495, 103 and Oehme, H.; Leissring, E. Tetrahedron 1981, 37, 753,
respectively.
S0276-7333(97)00176-3 CCC: $14.00 © 1997 American Chemical Society

3562 Organometallics, Vol. 16, No. 15, 1997
Notes
Sch em e 1a
Ta ble 1. Cr ysta llogr a p h ic Da ta
A. Crystal Data
empirical formula
PdC33H28BrClNP
691.32
yellow, irregular
formula weight
crystal color, habit
crystal dimensions (mm)
crystal system
no. reflections used for
unit cell determination
(2θ range) (deg)
ω scan peak width
at half-height
lattice parameters
a (Å)
0.290 × 0.200 × 0.350
orthorombic
25 (12.5-15.0)
0.22
10.266(2)
28.021(9)
10.009(2)
2879(2)Å3
P212121 (No. 19)
4
b (Å)
c (Å)
V (Å3)
space group
Z
D
calc (g/cm3)
1.595
a
(i) Pd(AcO)2/AcOH, 60 °C, 4 h; (ii) LiBr/EtOH, room
F000
µ
1384
21.81
temperature, 30 min; (iii) LiCl/EtOH, room temperature, 30
min; (iv) L, CHCl3, room temperature, 30 min.
(Mo KR) (cm-1
)
B. Intensity Measurements
diffractometer
radiation
temperature (°C)
Rigaku AFC6S
Mo KR (λ ) 0.71069 Å)
17
take-off angle (deg)
detector aperture (mm)
6.0
6.0 horizontal
6.0 vertical
285
crystal to detector
distance (mm)
scan type
ω
scan rate (deg/min)
scan width (deg)
2θmax (deg)
no. of reflections
measured
4.0 (in omega) (3 rescans)
0.94 + 0.30 tan θ
50.1
total: 2606
corrections
Lorentz-polarization absorption
(trans. factors: 0.88-1.00)
decay (-2.70% decline)
C. Structure Solution and Refinement
structure solution
Patterson method
refinement
full-matrix least-squares
function minimized
least-squares weights
p-factor
∑w(|Fo| - |Fc|)2
4Fo2/σ2(Fo
)
2
0.03
anomalous dispersion
no. observations (I > 3.00σ(I))
no. variables
reflection /parameter ratio
residuals: R; Rw
goodness of fit indicator
max. shift/error in final cycle
maximum peak in final
diff map (e/Å3)
all non-hydrogen atoms
1818
178
10.21
0.054; 0.069
2.81
0.38
1.25
F igu r e 1. Crystal structure of 4a : selected bond lenghts
[Å] and angles [deg]: Pd(1)-Br(1) 2.469(2), Pd(1)-P(1)
2.251(4), Pd-N(1) 2.12(1), Pd(1)-C(1) 2.03(1), N(1)-C(7)
1.28(2), N(1)-C(8) 1.48(2), Br(1)-Pd(1)-P(1) 92.5(1), Br-
(1)-Pd(1)-N(1) 93.5(3), P(1)-Pd(1)-C(1) 93.5(4), N(1)-Pd-
(1)-C(1) 80.4(5).
minimum peak in final
-0.68
diff map (e/Å3)
and angles are similar to those reported for related
metallacycles,8 the absolute configuration of the imine
ligand is R and the iminic nitrogen and the phosphine
molecule adopt a trans arrangement.
The action of dppe on the optically active cyclo-
palladated derivatives 5a and 6b permits us to obtain
the free phosphines (RMN 31P: δ ) -7.6 and -0.5 for
trans-2-PPh2(CyOH) and Ph2PCH(OMe)Ph, respec-
tively),9 but the cyclopalladated compound [Pd(C-N)-
(dppe)]X formed does not permit an easy regeneration
of the resolving agent. Furthermore, careful workup
is needed to obtain the air sensitive phosphine trans-
Ph2PCH(OMe)Ph in the free state. The 31P NMR
spectrum obtained when the cyclopalladated compound
[Pd(2-{Z-(R)-CHMeNdCH-2′,6′-Cl2C6H3}C6H4)Cl]2 is
added to the solution containing the free phosphine
trans-2-PPh2(CyOH), shows that the absolute configu-
ration of the phosphine is 1S,2S in the first eluted
diastereoisomer (δ ) 41.8 ppm).10
The elution of compounds 5a and 6b (containing the
racemic phosphines as ligands) in a SiO2 column, using
chloroform-methanol (100/1 and 100/0.3, respectively)
as an eluent, allowed the separation of the two diaste-
reoisomers (see experimental procedure). The diaster-
1
eomeric ratios were determined by H NMR spectros-
copy (500 MHz), at room temperature, using the integral
intensities ratio of signals of methyl, methoxy, or
methinic protons, or by 31P NMR spectroscopy (101.26
MHz) at 240 K.
(8) (a) Albert, J ., Go´mez, M.; Granell, J .; Sales, J .; Solans, X.; Font-
Altaba, M. Organometallics 1986, 5, 2567. (b) Albert, J ., Go´mez, M.;
Granell, J .; Sales, J .; Solans, X. Organometallics 1990, 9, 1405. (c)
Albert, J .; Granell, J .; Sales, J .; Font-Bardia, M.; Solans, X. Organo-
metallics 1995, 14, 1393.
(9) A signal at δ ) 25.5, corresponding to the phosphine oxide, is
also observed when the reaction is carried on 6b.

Notes
The lability of the palladium-phosphorous bond in
Organometallics, Vol. 16, No. 15, 1997 3563
20 °C) of a saturated CHCl3 solution layered with MeOH, was
selected and mounted on Rigaku AFC6s diffractometer. Unit
cell parameters were determined from automatic centering of
25 reflections (12.5 e θ e 15°) and refined by the least squares
method. Intensities were collected with graphite monochro-
matized Mo KR radiation, using ω-scan technique. Reflections
having I g 3σ(I) were used for structure resolution. All
calculations for data reduction and structure solution and
refinement were carried out using the TEXSAN software
system.15 The palladium and bromine atoms were located by
Patterson synthesis, and the remaining non-hydrogen atoms
were found by the DIRDIF method16 and refined by full-matrix
least-squares method. Hydrogen atoms were included in
idealized positions. The final R factor was 0.054, (Rw ) 0.069)-
wR ) 0.134. The maximum and minimum peaks in the final
difference synthesis were 1.25 eÅ-3 and -0.68 eÅ-3, respec-
tively. Crystal parameters, data collection details, and results
of the refinements are summarized in Table 1.
cyclopalladated derivatives,4d and the fact that the main
objective of the resolution of phosphine ligands is the
synthesis of coordination compounds (that can be useful
reagents for enantioselective catalysis), prompted us to
study ligand transfer reactions between optically active
5a and 6b and some platinum compounds like PtCl2 or
trans-[PtCl(µ-Cl)(PPh3)]2 (in the molar ratio 2/1). When
these reactions were performed with the imine deriva-
tive 5a , the formation of mixtures of platinum coordina-
tion compounds was observed. But when the reactions
were performed with the amine derivative 6b, the
coordination platinum complexes trans-[PtCl2{Ph2PCH-
(OMe)Ph}2] 7 and trans-[PtCl2{Ph2PCH(OMe)Ph}(PPh3)]
8 were cleanly obtained from PtCl2 and trans-[PtCl(µ-
Cl)(PPh3)]2, respectively.11 Moreover, the dinuclear
cyclopalladated resolving agent 3b can be separated
from the platinum compounds and used in a new
resolution process.12 It should be noted that platinum
complexes [PtCl2(PR3)2] or [PtCl2(P-P)], in the presence
of SnCl2, are useful catalysts in the asymmetric hydro-
formylation of olefins.13
Ma ter ia ls a n d Syn th eses. All chemicals and solvents
were commercial and used as received, except ethanol, chlo-
roform, methanol, and acetone, which were dried over CaCl2
and distilled before use. Phosphines trans-2-PPh2(CyOH) and
Ph2PCH(OMe)Ph were prepared as described.7
(R)-2-ClC6H3CHdNCHMeC6H5. A 5 mmol amount (0.705
g) of 2-chlorobenzaldehyde was treated with 5 mmol (0.605 g)
of (R)-(+)-1-phenylethylamine in ethanol (30 mL) at reflux for
4 h and the resulting solution concentrated in vacuo. The oil
obtained contains the imine 1a (>95%) and was used without
further purification. 1a : 1H: 8.80 [s, 1H, CHdN], 8.12 [m,
1H, aromatic], 7.60-7.20 [m, 8H, aromatic], 4.60 [q, 3J (HH)
In conclusion, despite the low chemical yield of the
separation of the diastereoisomers, the process pre-
sented is a useful approach to the subject of the phos-
phine resolution because it allows, for the first time, the
synthesis of optically active platinum complexes and the
regeneration of the resolving agent in one step. Fur-
thermore, this sequence of reactions permits the syn-
thesis of the platinum coordination compounds without
the isolation of the free phosphine, thus preventing the
racemization or decomposition of this ligand.14 The
extension of this process to new cyclopalladated deriva-
tives and to new racemic ligands is currently under way.
3
) 6.6 Hz, 1H, CHMe], 1.60 [d, J (HH) ) 6.6 Hz, 3H, CHMe].
IR: νmax/cm-11635 (CdN).
Syn th esis of 2 a n d 3. A stirred suspension of Pd(AcO)2
(2.2 mmol, 0.5 g) in acetic acid (25 mL) was treated with 2.2
mmol of the N-donor ligand (imine or amine) at 60 °C for 4 h
and the resulting solution concentrated in vacuo. The reaction
residue was treated with 4.4 mmol of LiBr or LiCl in ethanol
(25 ml) and the suspension stirred at room temperature for
30 min. The resulting solution was concentrated in vacuo, and
the solid obtained was purified by SiO2 column chromatogra-
phy. Compounds 2 and 3 were eluted with CHCl3/MeOH (100/
2) and isolated as yellow powders in yields of 50-70%, after
concentration of the solvents and addition of ethanol (10 mL).
2a : 1H: 8.10 [s, 2H, CHdN], 7.50-6.95 [m, 16 H, aromatic],
5.40 [br m, 2H, CHMe], 1.80 [br m, 6H, CHMe]. Anal. Calcd
(found) for C30H26Br2Cl2N2Pd2: C, 41.98 (42.2); H, 3.05 (3.3);
N, 3.27 (3.3). 3a : 1H: 8.05 [s, 2H, CHdN], 7.50-6.95 [m, 16H,
aromatic], 5.40 [br m, 2H, CHMe], 1.75 [br m, 6H, CHMe].
Anal. Calcd (found) for C30H26Cl4N2Pd2: C, 46.84 (47.0); H,
3.40 (3.4); N, 3.64 (3.6). 2b: 1H: 7.40-6.70 [m, 8 H, aromatic],
4.35 [br m, 2H, CHMe], 4.05 [br m, 2H, NH], 3.20 [br m, 2H,
NH], 1.60 [br m, 6H, CHMe]. Anal. Calcd (found) for
Exp er im en ta l Section
1H NMR spectra at 200 MHz and 500 MHz, and 31P{1H}
spectra at 101.26 MHz, were recorded, respectively, on Varian
Gemini 200, Varian VXR 500, and Bruker DRX 250 spectrom-
eters. Chemical shifts (in ppm) were measured relative to
SiMe4 for 1H and to 85% H3PO4 for 31P. The solvents used
were CDCl3 in 1H and CHCl3 in 31P. Microanalyses were
performed at the Institut de Qu´ımica Bio-Orga`nica de Barce-
lona and the Serveis Cient´ıfico-Te`cnics de la Universitat de
Barcelona.
Cr ysta llogr a p h ic Stu d ies. A crystal (0.29 × 0.2 × 0.35
mm), obtained by slow evaporation (at room temperature ca
(10) Albert, J .; Granell, J .; Muller, G.; Sainz, D.; Font-Bardia, M.;
Solans, X. Tetrahedron: Asymmetry 1995, 6, 325.
C
16H20Br2N2Pd2: C, 31.34 (31.3); H, 3.29 (3.3); N, 4.57 (4.5).
3b: 1H: 7.40-6.70 [m, 8H, aromatic], 4.30 [br m, 2H, CHMe],
4.15 [br m, 2H, NH], 3.20 [br m, 2H, NH], 1.65 [br m, 6H,
CHMe]. Anal. Calcd (found) for C16H20Cl2N2Pd2: C, 36.67
(36.3); H, 3.85 (3.9); N, 5.35 (5.5).
(11) The reaction between the free phosphine Ph2PCH(OMe)Ph and
the platinum compound trans-[PtCl(µ-Cl)(PPh3)]2, in a molar ratio 2/1,
affords a complex mixture of coordination platinum compounds, but
when the reaction was undertaken using the cyclopalladated derivative
6b, as a source of the phosphine ligand, only the compound trans-
[PtCl2{Ph2PCH(OMe)Ph}(PPh3)] was obtained. Probably the use of the
palladium complex 6b, as a phosphine source, assures a low concentra-
tion of this ligand in solution, that prevents the formation of the
mixtures of coordination complexes.
Syn th esis of 4a a n d 4b. A suspension formed by 0.37
mmol of 2, 0.74 mmol of PPh3, and 20 mL of CHCl3 was stirred
at room temperature for 30 min and the resulting suspension
or solution concentrated in vacuo. Addition of ether (10 mL)
to the reaction residue produces the precipitation of compounds
(12) The intensity of the signals in the NMR spectrum of 7 shows
that this reaction does not change the optical enrichment of the
phosphine.
1
4 as white or pale yellow powders in yields of 80%. 4a : H:
(13) (a) Parinello, G.; Stille, J . K. J . Am. Chem. Soc. 1987, 109, 7122.
(b) Kollar, L.; Consiglio, G.; Pino, P. J . Organomet. Chem. 1987, 330,
305. (c) Go´mez, M.; Muller, G.; Sainz, D.; Sales, J . Organometallics
1991, 10, 4036. (d) Botteghi, C.; Paganelli, S.; Schionato, A.; Marchetti,
M. Chirality 1991, 3, 355. (e) Agbossou, F.; Carpentier, J . F.; Mortreux,
A. Chem. Rev. 1995, 95, 2485. (f) Scrivanti, A.; Beghetto, V.; Bastianini,
A.; Matteoli, U.; Menchi, G. Organometallics 1996, 15, 4687.
(14) The functionalized phosphine Ph2PCH(OMe)Ph is readily oxi-
dizable and should be stored under nitrogen but, when coordinated to
palladium, this ligand becomes very stable and can be stored several
months in air.
8.65 [d, 1H, J (HP) ) 7.6 Hz, CHdN], 7.80-7.70 [m, 6H,
(15) TEXSAN: Single-Crystal Structure Analysis Software, version
5.0; Molecular Structure Corp.: The Woodlands, TX, 1989.
(16) Beurskens, P. T.; Bosman, W. P.; Doesburg, H. N.; Gould, R.
D.; van der Hark, T. E.; Prick, P. A. J .; Nordik, J . H.; Beurskens, G.;
Partasarati, V. DIRDIF, an automatic procedure for phase extension
and refinement of difference structure factors; Technical Report 1981/
2, Crystallographic Laboratory Toernooiveld: Nijmegen, The Nether-
lands, 1981.

3564 Organometallics, Vol. 16, No. 15, 1997
Notes
aromatic], 7.50-7.25 [m, 14 H, aromatic], 6.80 [d, J (HH) )
8.0 Hz, 1H, aromatic], 6.45-6.20 [m, 3H, aromatic and CHMe],
1.80 [d, J (HH) ) 7.0 Hz, 1H, CHMe]. 31P: 43.5, s. Anal. Calcd
(found) for C33H28BrClNPPd: C, 57.33 (57.5); H, 4.08 (4.3); N,
2.03 (2.0). 4b: 1H: 7.80-7.70 [m, 6H, aromatic], 7.60-7.20
[m, 9H, aromatic], 7.00-6.80 [m, 2H, aromatic], 6.50-6.30 [m,
2H, aromatic], 4.60 [br m, 1H, CHMe], 4.15 [br m, 1H, NH],
3.55 [br m, 1H, NH], 1.75 [br m, 3H, CHMe]. 31P: 42.3, s.
Anal. Calcd (found) for C26H25BrNPPd: C, 54.90 (54.9); H,
4.43 (4.5); N, 2.46 (2.6).
3H, CHMe]. 31P: 46.3, s; 44.8, s. Anal. Calcd (found) for
C
28H29ClNOPPd: C, 59.17 (58.9); H, 5.13 (5.1); N, 2.46 (2.4).
Sep a r a tion of 5a Dia ster eoisom er s. Compound 5a was
carefully eluted at room temperature, in a SiO2 column (30 ×
400 mm, 40 g of SiO2) with CHCl3-MeOH (100/1) as eluent.
The first band eluted was collected in fractions of 25 mL,
1
concentrated in vacuo, and checked by H NMR spectroscopy.
The fractions of the optical pure compound (by 200 MHz 1H
NMR spectroscopy) were selected using the methinic or the
methylic proton signals. From 200 mg of 5a (50/50), 20 mg
were obtained with a de higher than 95%.
Syn th esis of 5a a n d 5b. A suspension formed by 0.37
mmol of 3, 0.74 mmol of trans-2-PPh2(CyOH), and 20 mL of
CHCl3 was stirred at room temperature for 30 min, and the
resulting solution was concentrated in vacuo. Addition of ether
(10 mL) to the reaction residue produces the precipitation of
compounds 5 as pale yellow powders in a yield of 80-90%. 5a
(50/50): 1H: 8.40 [d, J (HP) ) 7.6 Hz, 1H, CHdN], 8.25 [d,
J (HP) ) 7.6 Hz, 1H, CHdN], 8.15-7.80 [m, 8H, aromatic],
7.70-7.20 [m, 22H, aromatic], 6.85 [d, J (HH) ) 8.0 Hz, 1H,
aromatic], 6.80 [d, J (HH) ) 8.0 Hz, 1H, aromatic], 6.55 [t,
J (HH) ) 8.0 Hz, 1H, aromatic], 6.50 [t, J (HH) ) 8.0 Hz, 1H,
aromatic], 6.40 [t, J (HH) ) 8.0 Hz, 2H, aromatic], 6.10 [m,
2H, CHMe], 3.20-2.80 [br m, aliphatic], 2.30-2.10 [br m,
aliphatic], 1.90-1.45 [br m, aliphatic], 1.80 [d, J (HH) ) 7.3
Hz, 6H, CHMe], 1.40-0.80 [br m, aliphatic]. 31P: 44.4, s; 43.6,
s. Anal. Calcd (found) for C33H34Cl2NOPPd: C, 59.26 (59.7);
H, 5.12 (5.2); N, 2.10 (2.1). 5b (50/50): 1H: 8.15-7.95 [m, 8H,
aromatic], 7.65-7.45 [m, 12H, aromatic], 6.90-6.80 [m, 4H,
aromatic], 6.45-6.30 [m, 4H, aromatic], 5.00 [br m, 1H, NH],
4.73 [br m, 1H, NH], 4.70 [br m, 2H, CHMe], 4.28 [br m, 1H,
NH], 3.90 [br m, 1H, NH], 3.45-3.20 [br m, 1H, NH], 3.20-
2.80 [br m, aliphatic], 2.00-1.90 [br m, aliphatic], 1.90-1.45
[br m, aliphatic], 1.80 [d, J (HH) ) 6.4 Hz, 3H, CHMe], 1.63
[d, J (HH) ) 6.4 Hz, 3H, CHMe], 1.25-1.0 [br m, aliphatic].
Sep a r a tion of 6b Dia ster eoisom er s. Compound 6b was
carefully eluted at room temperature, in a SiO2 column (30 ×
400 mm, 40 g of SiO2) with CHCl3-MeOH (100/0.3) as eluent.
The first band eluted was collected in fractions of 25 mL,
1
concentrated in vacuo, and checked by H NMR spectroscopy.
The fractions of the optical purity desired were selected using
the methoxy proton signals. From 200 mg of 6b (50/50) can
be isolated 25 mg of the same compound in de higher than
95%.
Syn th esis of 7. A suspension formed by 0.14 mmol (0.08
g) of 6b (de 95%) was treated with 0.14 mmol (0.036 g) of PtCl2,
in 20 mL of acetone-methanol (85-15) at reflux for 1.30 h.
The resulting solution was concentrated to dryness in vacuo,
5 mL of methanol was added to the solid formed, and the
mixture was stirred for 5 min. The insoluble residue formed
was characterized as compound 7. The methanolic solution
was concentrated in vacuo to dryness to recover 3b . The
yield of the process is 60%. 7: 31P: 23.4 [d, J (P-Pt) ) 2570
Hz], 23.5 [d, J (P-Pt) ) 2570 Hz]; Anal. Calcd (found) for
C
40H38Cl2O2P2Pt: C, 54.67 (54.4); H, 4.36 (4.2).
Syn th esis of 8. A suspension formed by 0.14 mmol (0.08
g) of 6b (de 95%) was treated with 0.14 mmol (0.156 g) of trans-
[PtCl(µ-Cl)(PPh3)]2, in 20 mL of acetone-methanol (85-15) at
reflux for 1.30 h. The resulting solution was concentrated to
dryness in vacuo, 5 mL of methanol was added to the solid
obtained, and the mixture was stirred at room temperature
for 5 min. The insoluble residue formed was characterized as
compound 8. The methanolic solution was concentrated in
vacuo to dryness to recover 3b. The yield of the process is
70%. 8: 31P: 23.2 and 18.5 [AB quartet, J (P-Pt) ) 2570 Hz,
J (P-Pt) ) 2621 Hz, J (P-P) ) 478 Hz.]. Anal. Calcd (found)
for C38H34Cl2OP2Pt: C, 54.69 (54.7); H, 4.08 (4.0).
31P: 46.7, s; 45.5, s. Anal. Calcd (found) for C26H31
ClNOPPd: C, 57.16 (57.4); H, 5.71 (5.8); N, 2.56 (2.4).
-
Syn th esis of 6a a n d 6b. A suspension formed by 0.37
mmol of 3, 0.74 mmol of Ph2PCH(OMe)Ph, and 20 mL of CHCl3
was stirred under nitrogen at room temperature for 30 min
and the resulting solution concentrated in vacuo. The solid
obtained was eluted by SiO2 column chromatography with
CHCl3/MeOH (100/1) as eluent. Compounds 6 were isolated
as yellow solids in a yield of 70-80%. 6a (50/50): 1H: 8.50
[d, J (HP) ) 7.5 Hz, 1H, CHdN], 8.25 [d, J (HP) ) 7.5 Hz, 1H,
CHdN], 8.10-7.80 [m, 8H, aromatic], 7.70-7.20 [m, 32H,
aromatic], 6.95 [m, 2H, aromatic], 6.75 [m, 4H, aromatic, HC-
(OMe)], 6.40 [m, 2H, CHMe], 6.10 [t, 2H, aromatic], 3.35 [s,
3H, OMe], 3.30 [s, 3H, OMe], 1.85 [d, J (HH) ) 6.6 Hz, 3H,
CHMe], 1.80 [d, J (HH) ) 6.6 Hz, 3H, CHMe]. 31P: 45.2, s;
44.9, s. Anal. Calcd (found) for C35H32Cl2NOPPd: C, 60.84
(60.8); H, 4.67 (4.5); N, 2.03 (2.0). 6b (50/50): 1H: 8.25-8.00
[m, 4H, aromatic], 7.60-7.30 [m, 10H, aromatic], 7.25-7.00
[m, 16H, aromatic], 6.70-6.60 [m, 4H, aromatic], 6.40-6.30
[m, 6H, aromatic and HC(OMe)], 4.45 [br m, 1H, CHMe], 4.40
[br m, 1H, CHMe], 4.00 [br m, 1H, NH], 3.90 [br m, 1H, NH],
3.45-3.20 [br m, 2H, NH], 3.35 [s, 3H, OMe], 3.30 [s, 3H, OMe],
1.70 [d, J (HH) ) 6.6 Hz, 3H, CHMe], 1.65 [d, J (HH) ) 6.6 Hz,
Ack n ow led gm en t . We thank the DGICYT (proj-
ect: PB 93-0804) and the Comissionat per a Universi-
tats i Recerca (project: 1995SGR 00044) for financial
support.
Su p p or tin g In for m a tion Ava ila ble: Full details of the
X-ray structure of 4a , including tables listing positional
parameters, all bond lengths and angles, and isotropic and
anisotropic displacement parameters (13 pages). Ordering
information is given on any current masthead page.
OM970176I