'Melen complexes': A new family of Schiff base metal chelates derived from di-Meldrum's acid derivatives

Article abstract of DOI:10.1016/j.tetlet.2010.08.018

A new family of N₂O₂-tetradentate ligands and complexes derived thereof, based on Meldrum's acid and diamines, has been developed. The structure of 7b has been unequivocally established by an X-ray crystallographic study. The general strategy has been successfully applied to the synthesis of a tridentate ligand that when reacted with Et₂Zn resulted in the formation of a coordinatively linked dimer.

Full text of DOI:10.1016/j.tetlet.2010.08.018

Tetrahedron Letters 51 (2010) 5543–5545
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
‘Melen complexes’: a new family of Schiff base metal chelates derived
from di-Meldrum’s acid derivatives
*
Antonio Garrido Montalban , Jorge Alonso, Andrew J. P. White, David J. Williams
Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London SW7 2AY, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
A new family of N2O2-tetradentate ligands and complexes derived thereof, based on Meldrum’s acid and
diamines, has been developed. The structure of 7b has been unequivocally established by an X-ray crys-
tallographic study. The general strategy has been successfully applied to the synthesis of a tridentate
ligand that when reacted with Et2Zn resulted in the formation of a coordinatively linked dimer.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 16 April 2010
Revised 4 August 2010
Accepted 7 August 2010
Available online 11 August 2010
Since their discovery in the 1860s,1 Schiff base (SB) complexes
continue to play an important role in the development of main
group and transition metal coordination chemistry.2 This is due
to their preparative accessibility, diversity, and structural variability
and to the fact that, in particular those with N2O2-tetradentate li-
gands have been recognized as useful models for metallobiosites.
The most important early contribution, with respect to the latter,
was provided by Jacobsen3 and Katsuki4 in the early 1990s, who
extended the principles of cytochrome P-450 reactivity to the
asymmetric epoxidation of unfunctionalized olefins using homo-
chiral salen-type manganese(III) SB catalysts. Since then, there
has been a resurgence of interest in chiral salen-type ligands as
scaffolds for asymmetric catalysis and many second-generation
salen-complexes for oxo transfer5 and other reactions6 have been
developed.
family of N2O2-tetradentate Schiff base complexes derived from
Meldrum’s acid and o-phenylene-diamines. In addition, we show
that through reaction with aliphatic 1,2-diamines, chiral-tetraden-
tate, and tridentate ligands and metal complexes derived thereof
can be obtained for which an example of each is given. By analogy
with salen-complexes, we have termed this new family of metal
chelates ‘melen-complexes’.
Thus, a series of novel and known di-Meldrum’s acid derivatives
2a–g were conveniently prepared by refluxing o-phenylene dia-
mines 1a–g with 2 equiv of 5-methoxymethylene Meldrum’s acid11
(generated in situ) in trimethyl orthoformate (Table 1). At this stage,
It is well-known in homogeneous asymmetric catalysis that
although sterics play the major role in the asymmetric induction
mechanism, electronic effects have also been shown to be quite
important.7 However, of the many effective chiral ligands, only a
few are synthetically or structurally well-suited to electronic
tuning and hence optimization. Therefore, the ability to easily syn-
thesize a series of structurally similar ligands with subtle steric and
electronic variations is highly desirable. Meldrum’s acid is an easily
prepared and versatile reagent8 which is more acidic than acyclic
Scheme 1.
malonate esters, due to better p-orbital overlap of the resultant an-
ion within the cyclic structure,9 and as such potentially useful for
the development of novel metal-chelating agents. The synthesis
of o-phenylenediamine-bis(methylene Meldrum’s acid) derivatives
(Scheme 1) was co-developed and reported by the main author in
2002 for the elaboration of 1,10-phenanthrolines.10 The above con-
siderations, in addition to the topological similarity between these
systems and salen-type SB ligands prompted us to study their
metal-chelating properties. Thus, herein we now report a new
Table 1
Synthesis of di-Meldrum’s acid derivatives from o-phenylene diamines according to
Scheme 1
Entry
Diamine
R1
R2
Product
Yield (%)
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1f
H
H
H
H
H
Me
NO2
H
2a10
2b10
2c
70
82
42
34
35
84
39
Me
NO2
Cl
OMe
H
2d10
2e
2f
2g
* Corresponding author.
E-mail address: amontalban@arenapharm.com (A.G. Montalban).
1g
H
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.08.018

5544
A. G. Montalban et al. / Tetrahedron Letters 51 (2010) 5543–5545
Scheme 2.
Figure 1. The molecular structure of 7b.
cleared and turned orange after 30 min. After reflux for 3 h, the sol-
vent was rotary evaporated and the red-orange solids obtained were
dried under vacuum. All spectroscopic data13 were consistent with
the proposed structures except for complexes 3f and g that resisted
adequate characterization due to solubility issues. Similarly, reac-
tion of (R,R)-1,2-diaminocyclohexane with Meldrum’s acid (vide su-
pra) followed by treatment of the intermediate chiral N2O2-
tetradentate ligand 4 with Ni(OAc)2.4H2O in refluxing ethanol re-
sulted again in the quantitative formation of complex 5 as a red solid
(Scheme 3).14 On the other hand, the same reaction, but with
Zn(OAc)2ꢀ2H2O instead, was not as efficient. However, when 4 was
treated with1 equiv of Et2Zn15 (1.0 M solution in hexane) at ambient
temperature in dichloromethane, the corresponding zinc-complex 6
was obtained quantitatively (Scheme 3). The analogous reaction of
2a–g with Et2Zn resulted in the quantitative formation of metal che-
lates 7a–g (Scheme 4).
Scheme 3.
Scheme 4.
In contrast, to compounds 3f and g, the corresponding
Zn-complexes 7f and g were soluble enough to allow adequate
characterization.16 In addition, crystals of complex 7b suitable for
X-ray crystallography were obtained from DMSO.17 The structure
of 7b (Fig. 1) shows the zinc to have adopted a square pyramidal
coordination geometry with the DMSO oxygen atom occupying
the apical site; the metal lies ca. 0.41 Å out of the N2O2 basal plane
which is coplanar to better than 0.01 Å.
Finally, the strategy was applied to the synthesis of a tridentate
Meldrum’s acid derivative (Scheme 5). Thus, reaction of N,N-
dimethylethane-1,2-diamine with Meldrum’s acid under the above
general conditions gave the desired tridentate ligand 8 in 79% yield
(Scheme 5).
no attempts were made to further optimize the reaction conditions.
In the case of 2e, however, 2 equiv of triethylamine were added to
the reaction mixture in order to neutralize the commercially avail-
able dihydrochloride salt of 1e.12 With the requisite N2O2-tetraden-
tate ligands in hand, next, we turned our attention to explore their
metal-coordinating properties. To simplify the characterization,
we decided to start with the synthesis of diamagnetic d8 Ni(II)-com-
plexes which we rendered suitable due to the cation size and pre-
ferred coordination geometry (square planar). Indeed, when di-
Meldrum’s acid derivatives 2a–g were treated with 1 equiv of
Ni(OAc)2ꢀ4H2O in refluxing ethanol, the novel SB complexes 3a–g
were formed quantitatively (Scheme 2). The initial suspensions
Scheme 5.

A. G. Montalban et al. / Tetrahedron Letters 51 (2010) 5543–5545
5545
8. (a) Chen, B.-C. Heterocycles 1991, 32, 529; (b) Dumas, A. M.; Fillion, E. Acc. Chem.
Res. 2010, 43, 440.
9. McNab, H. Chem. Soc. Rev. 1987, 7, 345.
10. Graf, G. I.; Hastreiter, D.; da Silva, L. E.; Rebelo, R. A.; Garrido Montalban, A.;
McKillop, A. Tetrahedron 2002, 58, 9095.
11. Bihlmayer, G. A.; Derflinger, G.; Derkosch, J.; Polansky, O. E. Monatshefte 1967,
98, 564.
Subsequent treatment of 8 with 0.5 equiv of Et2Zn in dichloro-
methane at ambient temperature gave complex 9 as a pale yellow
solid in quantitative yield (Scheme 5). Both, NMR- and high resolu-
tion MS-data were consistent with the proposed dimer structure.18
Interestingly, reaction of 8 with Ni(OAc)2ꢀ4H2O under the above
conditions resulted only in recovery of the starting material.
In summary, we have developed a new family of N2O2-tetraden-
tate ligands and complexes derived thereof by combining
Meldrum’s acid with a variety of diamines. By analogy with
salen-complexes, and due to the ease of synthesis and suitability
to electronic tuning, melen-complexes should have rich and varied
catalytic activities. Such properties are currently being investigated
and will be reported in due course.
12. Synthetic procedure for the preparation of di-Meldrum’s acid derivative 2e: The
general procedure was followed except that 2 equiv of Et3N was added to the
reaction mixture. Thus, Meldrum’s acid (0.68 g, 4.72 mmol) was gently
refluxed in CH(OMe)3 (6.8 mL) for 2 h. After this time, the dihydrochloride
salt of diamine 1e (0.50 g, 2.36 mmol) was added followed by Et3N (2 equiv,
0.66 mL) and the resulting mixture further refluxed for 2 h. The reaction
mixture was allowed to cool, the solvent rotary evaporated and the residue
was re-dissolved in EtOAc (50 mL). The organic layer was washed with H2O
(3 ꢁ 50 mL), dried (MgSO4) and rotary evaporated. The residue was triturated
with Et2O and filtered to give 2e (0.37 g, 35%) after drying as an off-white solid.
13. Selected data for complexes 3c and d: (3c) 1H NMR (CDCl3, 300 MHz) d 1.73 (s,
12H), 7.64 (d, J = 9.0 Hz, 1H), 8.06 (d, J = 9.0 Hz, 1H), 8.42 (s, 1H), 8.83 (s, 2H).
(3d) 1H NMR (CDCl3, 300 MHz) d 1.71 (s, 12H), 7.12 (dd, J = 1.8 and 8.8 Hz, 1H),
7.43 (d, J = 8.8 Hz, 1H), 7.49 (d, J = 1.7 Hz, 1H), 8.22 (s, 2H).
Acknowledgments
14. Selected data for ligand 4: 1H NMR (CDCl3, 300 MHz) d 1.44 (t, J = 9.9 Hz, 2H),
1.65 (s, 6H), 1.67 (s, 6H), 1.73 (d, J = 9.1 Hz, 2H), 1.93 (d, J = 8.6 Hz, 2H), 2.22 (d,
J = 13.4 Hz, 2H), 3.42–3.48 (m, 2H), 8.07 (d, J = 14.5 Hz, 2H), 9.60 (dd, J = 7.2 and
14.5 Hz, 2H). HRMS (FAB) calcd for C20H26N2O8: [M+] 422.1689, found [M+]
We thank Professor A. G. M. Barrett and the Spanish Govern-
ment (J.A.) for generous support of our studies.
422.1683. ½a 2D0
ꢂ : ꢃ179.5 (c 2, CHCl3).
References and notes
15. Morris, G. A.; Zhou, H.; Stern, C. L.; Nguyen, S. T. Inorg. Chem. 2001, 40, 3222.
16. Selected data for Zn-complex 7g: 1H NMR (DMSO-d6, 300 MHz) 1.70 (s, 12H),
7.20 (d, J = 9.0 Hz, 1H), 7.33 (t, J = 9.0 Hz, 1H), 7.84 (d, J = 9.0 Hz, 1H), 8.21 (s,
1H), 8.88 (s, 1H). HRMS (FAB) calcd for C20H18N3O10Zn: [M+] 524.0284, found
1. Yamada, S. Coord. Chem. Rev. 1999, 190–192, 537.
2. Mederos, A.; Dominguez, S.; Hernandez-Molina, R.; Sanchiz, J.; Brito, F. Coord.
Chem. Rev. 1999, 193–195, 857.
3. Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990,
112, 2801.
4. Irie, R.; Noda, K.; Ito, Y.; Matsumoto, N.; Katsuki, T. Tetrahedron Lett. 1990, 31,
7345.
[M+] 524.0269.
17. Crystal data for 7b:
ꢀ
C
23H26N2O9SZn, M = 571.89, triclinic, P1 (no. 2),
a = 9.3283(12),
b = 78.736(10),
b = 12.4948(16),
c = 13.1171(17)
Å,
a = 61.859(9),
c
= 69.129(9)°, V = 1259.0(3) Å3, Z = 2, Dc = 1.509 g cmꢃ3
,
l
(MoKa , T = 293 K, yellow diamond prisms, Siemens P4
) = 1.113 mmꢃ1
5. Katsuki, T. Coord. Chem. Rev. 1995, 140, 189.
diffractometer; 4258 independent measured reflections (Rint = 0.0234), F2
refinement, R1(obs) = 0.0358, wR2(all) = 0.0894, 3564 independent observed
6. (a) Saito, B.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3873. and references cited
therein; (b) Belokon, Y. N.; Green, B.; Ikonnikov, N. S.; North, M.; Parsons, T.;
Tararov, V. I. Tetrahedron 2001, 57, 771; (c) Shyu, H.-L.; Wei, H.-H.; Lee, G.-H.;
Wang, Y. J. Chem. Soc., Dalton Trans. 2000, 911; (d) Balsells, J.; Walsh, P. J. J. Org.
Chem. 2000, 65, 5005; (e) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259; (f)
Yoon, T. P.; Jacobsen, E. N. Science 2003, 299, 1691. and references cited therein.
7. (a) Campbell, E. J.; Nguyen, S. B. T. Tetrahedron Lett. 2001, 42, 1221. and
references cited therein; (b) Katsuki, T. Chem. Soc. Rev. 2004, 33, 437.
absorption-corrected reflections [|F0| > 4r(|F0|), 2hmax = 50°], 332 parameters.
CCDC 773195.
18. Selected data for complex 9: 1H NMR (DMSO-d6, 300 MHz) 1.65 (m, 12H), 2.25
(s, 12H), 2.42–2.58 (m, 2H), 2.67–2.81 (m, 2H), 3.42–3.52 (m, 2H), 3.61–3.69
(m, 2H), 8.54 (s, 2H). HRMS (FAB) calcd for C22H35N4O8Zn: [M+H]+ 547.1746,
found [M+H]+ 547.1716.