Stereospecific co-crystallization of reactant and palladium complex in the resolution of stilbendiamine using N*-chiral ortho-palladated matrix

Article abstract of DOI:10.1016/S0957-4166(98)00176-1

Resolution of racemic 1,2-diphenyl-1,2-ethanediamine was performed through recrystallization of its diastereomeric adducts 2a,b with N*-chiral ortho-palladated complex (S(C)R(N))-1. The structure and absolute configuration of the less soluble (S(C)R(N),SS)-2a diastereomer was determined by X-ray diffraction. The complex has an unusual dimeric structure with a palladacycle:diamine ratio of 2:3; the association of 2a with an additional diamine molecule of the same (SS) absolute configuration is achieved due to hydrogen bonds between the coordinated and solvate diamine.

Full text of DOI:10.1016/S0957-4166(98)00176-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1917–1921
Stereospecific co-crystallization of reactant and palladium
complex in the resolution of stilbendiamine using N*-chiral
ortho-palladated matrix
V. V. Dunina,a,∗ L. G. Kuz’mina,b A. G. Parfyonov a and Yu. K. Grishin a
aDepartment of Chemistry, M. V. Lomonosov Moscow State University, 119899, V-234, Moscow, Russia
bN. S. Kurnakov Institute of General and Inorganic Chemistry RAS, Leninsky prosp. 31, 117907, Moscow, Russia
Received 19 March 1998; accepted 30 April 1998
Abstract
Resolution of racemic 1,2-diphenyl-1,2-ethanediamine was performed through recrystallization of its diastereo-
meric adducts 2a,b with N*-chiral ortho-palladated complex (SCRN)-1. The structure and absolute configuration of
the less soluble (SCRN,SS)-2a diastereomer was determined by X-ray diffraction. The complex has an unusual
dimeric structure with a palladacycle:diamine ratio of 2:3; the association of 2a with an additional diamine
molecule of the same (SS) absolute configuration is achieved due to hydrogen bonds between the coordinated
and solvate diamine. © 1998 Elsevier Science Ltd. All rights reserved.
1. Introduction
During the last decade, homochiral ortho-palladated complexes have evolved into powerful tools for
the resolution of diverse substrates.1,2 As a rule, the resolution includes selective crystallization of one
(or both) diastereomeric 1:1 adduct(s). However, several examples of a palladium:substrate ratio of 2:1
in the isolated diastereomer are also known.3 In these instances the consumption of a rather expensive
resolving agent is increased twofold. We present below some preliminary results of C2-symmetric
diamine resolution which may be performed via the dimeric association with a palladacycle:substrate=2:3
ratio.
∗
Corresponding author. Fax: +7 (095) 932-88-46; e-mail: dunina@org.chem.msu.su
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00176-1

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2. Results and discussion
For the resolution of racemic 1,2-diphenyl-1,2-ethanediamine (abbreviation Stien), we have chosen
N*-chiral dimeric ortho-palladated complex (SCRN)-1 as the resolving agent. In the reaction of dimer
(SCRN)-1 with two molar equivalents of racemic Stien, the formation of a 1:1 mixture of diastereomeric
adducts (SCRN,SS)-2a and (SCRN,RR)-2b was detected by 1H NMR spectroscopy. After recrystallization
twice from MeCN, the less soluble diastereomer (SCRN,SS)-2a was obtained in a yield of 51% (25% with
respect to the total Pd) and in 88% de.4
To increase the efficiency of the resolving agent utilization, further experiments were conducted with
a Pd:Stien ratio of 1:2 so that the selective crystallization of one of the two diastereomers might be
accomplished.5 The less soluble diastereomer (SCRN,SS)-2a was isolated under these conditions after
crystallization three times from methanol–ether in a yield of 44% (with respect to the total Pd) with
>98% de. However, our attempts to obtain the complex (SCRN,SS)-2a in an analytically pure state failed:
1
both the H NMR spectra and elemental analysis data7 indicated the inclusion of non-stoichiometric
amounts of the free Stien molecules in the crystalline adduct. This problem was solved by X-ray single
crystal analysis of this complex.
The molecular structure, numbering scheme and selected bond lengths and angles of the less sol-
uble diastereomer (SCRN,SS)-2a are presented in Fig. 1. The most interesting feature of the struc-
ture is the association of two symmetry center related mononuclear complex molecules with one co-
crystallization molecule of free diamine (SS)-Stien, [{(SCRN)-L}Pd{(SS)-Stien}Cl]2·(SS)-Stien 3a [L=2-
{1-(N-isopropylamino)ethyl}phenyl-C,N]. The association of the three molecules is due mainly to the
formation of the pair of hydrogen bonds N(3a)–H. . .N(20a) and N(3b)–H. . .N(20b) between NH groups
of coordinated diamines and N atoms of bridged solvate diamine, 2.281 Å. The pair of very weak
intermolecular agostic interactions Pd(1a). . .H–C(20a) and Pd(1b). . .H–C(20b), 3.05 Å, between the
orthogonally oriented ortho-H of Ph-groups of bridged diamine and palladium might also be proposed
as a factor of additional stabilization of this unusual structure.
The benzylaminate palladacycle has an envelope-like conformation with the bend along the
Pd(1). . .C(7) bond of 26.6° less puckered compared to the starting dimer (SCRN)-1; averaged intrachelate
torsion angles are 16.0 and 19.8–22.3°8 respectively. It retains the usual λ(SCRN)-stereochemistry with
i
the pseudo-axially oriented α-Me and N-Pri substituents; the short Pr. . .Pd contact at a distance of
2.858 Å should be noted.
The diamine metallacycle adopts a strongly twisted δ-conformation of the asymmetric envelope with
equatorial C–Ph groups and axial α-CH groups; the α-HCCH-α torsion angle is 179.6°. The average
intrachelate torsion angle is 32.2°. The chloride counterion forms two very strong hydrogen bonds with
the equatorial N–H groups of the same complex cation; one of these groups belongs to the benzylaminate
and another one to diamine chelate rings (Cl. . .H distances 2.447 and 2.477 Å, respectively).
The retention of the (λSCRN,δSS)-stereochemistry of the 2a diastereomer in solution was confirmed
by means of 1H NMR spectroscopy including NOE techniques [Fig. 2(a,b)].

V. V. Dunina et al. / Tetrahedron: Asymmetry 9 (1998) 1917–1921
1919
Fig. 1. X-Ray structure of adduct 3a. C32H40ClN4Pd, M 662.6, orthorhombic space group P21212, a 15.350(4), b 23.348(9),
c 8.396(1) Å, V 3009.1(14) Å3, Z 4, dcalc 1.374 g cm−3, Mo-Kα radiation, µ(Mo-Kα) 0.721 cm−1; 293 K; the final R and Rw
values are 0.0317 and 0.0789, respectively, for 3868 independent reflections corrected for absorption by a Ψ-scan curve
Fig. 2. Conformation of benzylaminate (a) and diamine (b) metallacycles
The identical (SS)-configuration of chelated and bridging Stien ligands9 prompted us to use this for
improvement of the preparative resolution procedure. In the reaction of dimeric complex (SCRN)-1 with
six molar equivalents of racemic diamine Stien under non-optimized conditions, the dimeric association
of the diastereomer (SCRN,SS)-2a with (SS)-Stien 3a with >98% de was obtained after its twofold
recrystallization from MeCN in an analytically pure state in a yield of 66% (with respect to the Stien
and the total Pd). Attempts to resolve the related C2-symmetric aliphatic diamine using the most popular
ortho-palladated complex (derived from 1-naphthylethylamine) have not been successful.6
The isolation of the free diamine (SS)-Stien from 3a was performed by its protonation with dilute
aqueous HCl in the two-phase system CH2Cl2/H2O in a yield of 85%. The resolving agent (SC,RN)-1
was recovered from the organic phase in essentially quantitative yield.
Although other routes to enantiopure Stien are also known (including resolution10 and asymmetric
synthesis11), the use of an ortho-palladated matrix for this purpose seems to be a very attractive approach.
To the best of our knowledge this is the first case of a double enantiomer selection (in the inner and

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V. V. Dunina et al. / Tetrahedron: Asymmetry 9 (1998) 1917–1921
outer coordination spheres) during the selective crystallization of the diastereomeric ortho-palladated
complexes and the first example of a structurally characterized palladium complex with stilbendiamine.
3. Experimental
3.1. Diastereomeric complex separation
A solution of racemic stilbendiamine (0.5904 g, 2.781 mM) in anhydrous MeOH (3 mL) was added
to a suspension of dimer (SCRN)-1 (0.282 g, 0.463 mM) in the same solvent (4 mL) under argon.
After 1 h stirring at room temperature the reaction mixture was filtered and evaporated in vacuo;
subsequent recrystallization (twice) of the oily residue from anhydrous MeCN afforded the solvated
adduct (SCRN,SS)-2a·0.5(Stien) in a yield of 66% (0.382 g, 0.614 mM) and a diastereomeric purity
1
20
(determined from H NMR data) of >98% de: m.p. (dec) 201–203°C, [α]D −39.4 (c 1.7, MeOH).
1
Anal. calcd: C, 61.74; H, 6.48; N, 9.00 for C32H40ClN4Pd. Found: C, 61.45; H, 6.51; N, 9.03. The H
NMR spectrum is the same as in the literature,7 except for the intensity of the free diamine signals.
3.2. Diamine isolation
A suspension of the individual diastereomer (SCRN,SS)-2a·0.5(Stien) (0.212 g, 0.341 mM) in CH2Cl2
(10 mL) was treated with aqueous 1 N HCl (5 mL) under vigorous shaking for 5 min; the aqueous phase
was extracted with CH2Cl2 (3×10 mL), concentrated in vacuo and treated with saturated KOH solution
under cooling. The diamine was thoroughly extracted with benzene and the combined organic extracts
were dried over KOH, concentrated in vacuo and treated with hexane. Diamine (SS)-Stien was isolated
20
in a yield of 85% (0.0923 g, 0.435 mM) and an optical purity of 99% ee: [α]D −106.2 (c 0.8, MeOH);
20
lit. data: [α]D −106.5 (c 1.09, MeOH).12
3.3. Resolving agent regeneration
The combined dichloromethane extracts from the diamine isolation (see Section 3.2) were washed
with water, dried over Na2SO4, and concentrated in vacuo. After chromatographic purification using a
short silica column, the starting dimer (SCRN)-1 was recovered in 95% yield (0.0985 g, 0.162 mM).
Acknowledgements
The financial support of this work by the Russian Foundation for Basic Research (grant 95-03-09227a)
is gratefully acknowledged.
References
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2. Examples of recent references: Chooi, Y. M., Ranford, J. D., Leung, P.-H., Mok, K. F., Tetrahedron: Asymmetry, 1994,
5, 1805–1814; Lim, C.-C., Leung, P.-H., Sim, K. Y., Tetrahedron: Asymmetry, 1994, 5, 1883–1886; Hockless, D. C. R.,
Mayadunne, R. C., Wild, S. B., Tetrahedron: Asymmetry, 1995, 6, 3031–3037; Dunina, V. V., Golovan’, E. B., Tetrahedron:
Asymmetry, 1995, 6, 2747; Pabel, M., Willis, A. C., Wild, S. B., Inorg. Chem., 1996, 35, 1244–1249.

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1921
3. Leung, P.-H., McLaughlin, G. M., Martin, J. W. L., Wild, S. B., Inorg. Chem., 1986, 25, 3392; Dai, L., Zhou, Zh., Zhang,
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Tetrahedron: Asymmetry, 1996, 7, 1027–1032.
20
4. For (SCRN,SS)-2a: m.p. (dec) 204–206°C, [α]D −34.3 (c 1.5, MeOH). Anal. calcd: C, 56.18; H, 6.41; N, 7.86 for
1
C25H32ClN3Pd·H2O. Found: C, 56.01; H, 6.14; N, 7.75. Diastereomeric purity (88% de) was determined by H NMR
using the integral intensity of the Me groups of the NPri substituent.
1
5. The H NMR spectra of the starting mixture of dimer (SCRN)-1 and racemic Stien in a 1:4 molar ratio contains two
sets of signals from the two diastereomers 2a,b in nearly a 1:1 ratio and the signals of free diamine. The absence
of stereoselectivity in their complexation seems to be a result of the low efficiency of steric interactions between the
benzylaminate palladacycle and the primary amino groups of the diamine (cf. findings of Leung et al.6); it is likely that the
disruption of the agostic interaction iso-Pr. . .Pd in a polar medium may decrease the conformational stability and ability
to chiral recognition of palladacycle as well.
6. Chooi, S. Y. M., Tan, M. K., Leung, P.-H., Mok, K. F., Inorg. Chem., 1994, 33, 3096.
20
7. For (SCRN,SS)-2a·0.3(Stien): m.p. (dec) 204–206°C, [α]D −50.0 (c 1.2, MeOH). Anal. calcd: C, 60.46; H, 6.39; N, 8.69
1
3
for C29.2H36.8ClN3.6Pd. Found: C, 60.57; H, 6.37; N, 8.79. H NMR (DMSO-d6, 40°C; δ, ppm; J, Hz): 1.247 (d, JHH
6.4, 3H, CHMe2), 1.254 (d, 3JHH 6.4, 3H, CHMe2), 1.693 (d, 3JHH 6.6, 3H, α-Me), 3.058 (m, 3JHH 6.4, JCH–NH 4.4, 1H,
3
CHMe2), 3.934 (br.t, JNH–NH 12.1, JNH–CH 9.0, 1H, N2Hax), 4.119 (q, JHH 6.7, 1H, α-CH of palladacycle), 4.222 (m,
2
3
3
1H, α-CH, Stien), 5.147 (br.t, 2JNH–NH 9.0, 3JNH–CH 12.0, 1H, N3Hax), 5.225 (br.d, 2JNH–NH 12.1, 1H, N2Heq), 5.524 (br.d,
2JNH–NH 9.0, 1H, N3Heq), 6.051 (d, 1H, JNH–CH 4.4, N1H of palladacycle), 7.15–7.40 (m, 13H, Ph, η2- and free Stien);
3
aromatic protons of palladacycle: 6.774 (dt, JHH 7.4, 4JHH 1.4, 1H, C5H), 6.911 (dt, 3JHH 7.2, 4JHH 0.8, 1H, C4H), 6.938
3
(dd, 3JHH 7.6, 4JHH 1.6, 1H, C3H), 7.040 (d, 3JHH 7.2, 1H, C6H); free Stien: 3.870 (br.s., 0.6H, α-CH).
8. Kuz’mina, L. G., Burtseva, O. Yu., Porai-Koshits, M. A., Dunina, V. V., Zalevskaya, O. A., Potapov, V. M., Zh. Obshch.
Khim. (Russ.), 1989, 59, 2525–2534 [J. Gen. Chem. USSR, 1989, 59 (Engl. Transl.)].
9. The same (SS)-configuration of both the η2- and µ-bonded Stien ligand was confirmed by 1H NMR: the addition of racemic
diamine to the solution of solvated complex 3a results in the appearance of the signals of the diastereomer (SCRN,RR)-2b.
10. Lifschitz, I., Bos, J. G., Rec. Trav. Chim. Pays-Bas, 1940, 59, 173; Saigo, K., Kubota, N., Takebayashi, Sh., Hasegawa, M.,
Bull. Chem. Soc. Jpn, 1986, 59, 931; Corey, E. J., Lee, D.-H., Sarshar, S., Tetrahedron: Asymmetry, 1995, 6, 3.
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Ohazaki, E., Tetrahedron Lett., 1992, 33, 5559; Shimizu, M., Kamei, M., Fujisawa, T., Tetrahedron Lett., 1995, 36, 8607.
12. Saigo, K., Kubota, N., Takebayashi, Sh., Hasegawa, M., Bull. Chem. Soc. Jpn, 1986, 59, 931.