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We have continued our ongoing efforts to discover enantioselective oxidation catalysts among a series of chiral metallophthalocyanine derivatives that have been synthesized in our laboratory.  These complexes can be grouped into two sub-classes.   One sub-class consists of the so-called “helmet” metallophthalocyanines of general formula L(diiPc)M, where diiPc is the 14,28-[1,3-diiminoisoindolinato]phthalocyaninato ligand, L is a labile alcohol or water ligand, and M represents (thus far) Fe(III) or Co(III).  The other sub-class is a series of alkoxy-modified nickel complexes of general formula [14, 28-(RO)₂Pc]Ni(II), where R represents Me, Et, n-Pr, n-Bu or b-hydroxyethoxy.  As it became apparent during the first grant year that our best prospects of isolating pure enantiomers of these compounds of interest is by application of HPLC techniques employing chiral stationary phases (CSPs) and because accomplishing this aim is a prerequisite to the realization of our overall goal of enantioselective catalyst discovery, we have concentrated our efforts over the past year in this area.

In our work with the nickel complexes [14, 28-(RO)₂Pc]Ni(II) we have optimized our analytical-scale HPLC methods, building upon preliminary results obtained during the first grant year, for the examples where R = Me, Et and n-Pr.  Optimization has been accomplished by systematic variation of temperature, non-aqueous mobile phase and base additives to provide baseline separation on a carbohydrate-based column.  In each case, resolution of 5.0 or greater, with selectivity in excess of 1.4 has been observed for the enantiomers.  Although we have not yet identified the separated enantiomers as (R, R) or (S, S), we are confident that true enantiomeric separation has in fact been achieved, based upon the fact that two distinct peaks of equal area are observed in chromatograms recorded with the detector set at varying wavelengths.  Because the optimal mobile phase in all three cases allows for good analyte solubility, we are confident that the analytical-scale results will soon be scaled to semi-preparative level, allowing full identification of the enantiomers and publication of these results.  More importantly, isolation of these complexes in sufficient quantity to allow for investigation of their catalytic behavior may allow the realization of our ultimate goal of discovering enantioselective oxidation catalysts from among the many chiral modified metallophthalocyanines that we have prepared thus far. 

In a further development related to our work with alkoxy-modified complexes [14, 28-(RO)₂Pc]Ni(II), we have now succeeded in fully characterizing the example where R = n-Pr, having recently obtained a satisfactory elemental analysis and established a bulk yield of 11% pure product based on starting Ni(II).  We now have characterized via single-crystal X-ray methods, IR, UV-VIS, and NMR (¹³C and ¹H) all three examples for which enantiomeric separation methods have been discovered.  Significant diastereotopic shifts have been observed for the a protons in the ethoxy and n-propoxy examples.  A smaller diastereotopic shift has been observed for the b protons in the propoxy-modified complex.  Assignments for ¹H signals in the propoxy complex have been confirmed by a ¹H-¹H COSY experiment.  The ¹³C spectra for all three compounds are very similar, showing sixteen unique signals corresponding to carbon atoms on the ligand heterocycle, plus the expected signals corresponding to the alkoxy groups –OR.  Thus, the C₂ symmetry observed in the solid state has been confirmed for the structure in solution as well.

We have attempted to extend our success in separating the enantiomers of the chiral nickel complexes described above via HPLC to the “helmet” complexes L(diiPc)Co and L(diiPc)Fe but the results of these efforts have thus far been less conclusive.  Several different stationary phases have been employed, including a range of carbohydrate- and glycoprotein-based phases.  We have observed indications of partial separation on carbohydrate-based phases, but this has been inconsistent for reasons that are not yet understood.  Given the sensitivity to minor changes in mobile phase, temperature, and even flow rate that are often observed for chiral separations, we remain confident, in spite of our difficulties up to this point, that careful and systematic variation of these parameters will allow us to find conditions that yield effective separations for the helmet complexes.