Ligands bispidine

Fig. 15. Left general representation of a bispidine ligand. Center example overlay of LFMM (red) and X-ray (blue) structure. Right comparison of LFMM and X-ray Cu-L bond lengths (A), arl and ar2 correspond to the R3 substituents.

Figure 9.6 Shape and size of the cavity of a highly asymmetric bispidine ligand reproduced with permission from reference[1861.

P. Comba, G. Rajaraman, H. Rohwer, A density functional theory study of the reaction of the biomimetic iron(II) complex of a tetradentate bispidine ligand with H2O2, Inorg. Chem. 46 (2007) 3826. 

THE TETRADENTATE BISPIDINE LIGAND DIMETHYL-(3,7-DIMETHYL-9-OXO-2,4-BIS(2-PYRIDYL)-3,7-DIAZABICYCLO[3.3.1]NONANE)-l,5-DICARBOXYLATE AND ITS COPPER(II) COMPLEX... 

First transition metal coordination compounds with bidentate bispidine ligands were described in 1957 (30). The initial report with metal complexes of tetradentate bispidine ligands dates back to 1969 (31). Following these early reports, there have been a number of studies on the complexation properties of several bipidine derivatives (32-35). However, extensive, broad, and thorough studies of the bispidine coordination chemistry began only <10 years ago. These studies will be reviewed here. They include structural and theoretical work, spectroscopy, electron-transfer studies, metal ion selective complexation, and applications in biomimetic chemistry, catalysis, and molecular magnetism. 

In addition and with reference to earlier work, which describes the synthesis of a bicyclic piperidone, derived from treating diethyl acetonedicarboxylate, an aldehyde and y-aminobutyraldehyde (79), it is possible to synthesize the bispidine derivative 57 with an unsymmetric substitution pattern (see Chart 6)(80). This Ending may be the basis for a whole new series of chiral bispidine ligands. 

From the 3,7-diacetyl compounds 68a and b (with R = CH3) the bispidinine dervatives 70a and b are obtained by heating in mineral acid. The resulting secondary amines open the door to introducing a variety of substituents, which are difficult to obtain with the Mannich approach to bispidine ligands. 

Additional strategies, which deviate from the synthetic pathways described above, include intramolecular cyclization reactions to obtain A,A -disubsti-tuted bispidine ligands. The cyclization may be started with N,N-his... 

Aromatic substituents at C2 and C4 are to some extent hindered in rotation. This leads to a third type of isomerism in bispidine chemistry (i.e., atropisomer-ism). The activation energy for the rotation around the C2/C4—aryl bond for bispidones with various meta-substituted phenyl groups was determined by various NMR methods and found to be 70-75 kJ mol (23). For a rotation of 180°, which is usually necessary for the coordination of bispidine ligands to metal ions (e.g., 14, see Scheme 14), two energy barriers have to be overcome. The higher is the result of an interaction of the ortho-disposed proton of the aromatic ring with the proton or the alkyl substituent at the N3 amine nitrogen atom. The... 

The most impressive parameter to show the rigidity of the bispidine ligands is the N3 - N7 distance, which is 2.9 A on average. The shortest distances are observed for tetrahedral copperfll) complexes of the bidentate ligand (49) and... 

Earlier force-field calculations (105) are at variance with these results and interpretations, but the stmctural data in Table IV and the experimentally determined complex stabilities (Table IX in Section in.D.2) support these predictions. Why this is so however is an interesting question. For the macro-cyclic ligand 74, there are, in contrast to complexes of the other bispidine ligands, smaller than average metal-donor distances (99). It appears that in this example the lone pairs are at an ideal orientation with respect to the metal center... 

The synthesis of the 2,4-bisphenol derivative of the standard tetradentate ligand 14 is quite tedious and so far has not been optimized (204). Apart from the fact that the noninnocent phenolate donors may lead to interesting ligand systems and metal complexes, it is the six-membered chelate rings involving the in-plane phenolate donors that lead to structural properties quite different from those of the other bispidine ligands [shown in Fig. 2(e) is a plot of a preliminary X-ray molecular structure of one of the possible conformers (meso form) of a copper(II) complex]. 

The piperidone precursor of 57 (see Chart 6) is a possible starting material for the synthesis of 2,6-substituted chiral, tetradentate bispidine ligands. The copper(II) complex of 57 is chiral [see Fig. 2(d) for a plot of the experimental structure] and has an interesting set of bond distances. Quite unexpectedly on the basis of the chelate ring sizes, the 2-pyridine substituent of the bispidine backbone is the axial donor (2.25 A), while N3 (2.08 A), N7 (2.05 A), the N7-pendant pyridine (2.01 A) and the chloride (2.28 A) are the in-plane donors (80). 

The rigidity of bispidine ligands has been analyzed on the basis of cavity size calculations with molecular mechanics [and density functional theory (DFT) — in order to check the accuracy and rehability of the force-field calculations] and a comparison of the computed and corresponding experimental structures and their analysis, based on the computed strain energy curves (42, 69, 189, 201). 

Figure 4. Hole size curves of bispidine ligands (molecular mechanics, no metal center-dependent energy terms included, see text broken lines are with sum constraints, solid lines are with an approach with individual, asymmetric variations of all six M—N bonds) of (a) 76, (b) 14, (c) 28, d) 24, (c) 32 (69).

III.B.l). The conclusion from the empirical force-field calculations is that all bispidine ligands are very rigid they do not change their shape along the entire curves, and this is in agreement with the observations from experimental structures (see Fig. 8 in Section III.D.1). However, there is a significant elasticity... 

Experimental Structural Parameters of Isomers of the CopperfI) Complexes of Various Bispidine Ligands"... 

Figure 13. The NMR spectra (200MHz, CDjCN) of the isomeric copper(I) conq>lexes of the tetradentate bispidine ligands 14 and 35 (a) temperature dependent spectra of [Cu(14)(NCCH3)]+ ...

The copper coordination chemistry of bispidine ligands has been studied extensively, and this has been particularly rewarding (70, 71, 81, 82, 168, 169, 192, 194, 196, 199, 201, 213, 214). The main reasons are that (1.) the bispidine backbone is complementary with respect to copper(ll) and, therefore, complex stabilities may be relatively high, comparable to those with macrocyclic ligands (69, 201), and that modifications of the ligand backbone can be used to tune the stabilities and redox potentials (199) (2.) due to the ligand rigidity, the copperfll)... 

Fenton chemistry (320-322) and indicates that ferryl species (at least when supported by bispidine ligands) rather than OH radicals may be involved in substrate oxidation. For iron(II) aqua ions, this has also been proposed on the basis of DFT calculations (323), and a similar mechanism is confirmed by DFT calculations with the bispidine complexes (174). 

III.B.2), complexes with manganese, chromium, as well as second- and third-row transition metal ions (e.g., ruthenium) oxidation reactions with dioxygen alone or with other peroxides (e.g., ferf-butyl-peroxide) the stabilization and spectroscopic characterization of mononuclear superoxo, peroxo, and oxo complexes other catalytic processes (e.g., the iron-catalyzed aziridination), enantioselective reactions with chiral bispidine ligands and the iron oxidation chemistry continues to produce novel and exciting results. 

An interesting possible further extension is the functionalization of bispidine ligands with hydrophobic groups, for example, for metal ion selective extractions (69, 339). biopolymers for nuclear medicinal applications (340), solids for heterogeneous catalysis and sensors, or additional coordination sites for the synthesis of heterodinuclear complexes with applications in biomimetic chemistry, catalysis, and as luminescence sensors. There is a variety of possible sites for ligand modification. Of particular interest is the C9 position, which has been selectively and stereospecifically reduced to an alcohol (190), and the two hydrolyzed C1,C5 ester groups (167). 

---