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Throughout the final year of this project we have employed the efficient, microwave–promoted, route to cobalt metallocenes that we developed and explored during the first two years of the award as a means to prepare organometallic scaffolds for applications in dynamic chemistry. Through both direct approaches—employing substituted acetylenes as direct metallocene precursors—and indirect routes where the required functionality was introduced at a later stage, we have been able to prepare viable quantities of metallocenes equipped with either formyl or carboxylic acid functionality. From these platforms dynamic (that is, reversible, and therefore thermodynamically controlled) chemistry of two distinct characters is possible: imine formation via the condensation of primary amines with formyl functions, and hydrazone formation via condensation of hydrazides with aldehydes. While this stage of the work remains in an exploratory phase, the extension and full exploration of which we hope to address with support from a future award, results from the past year suggest that the unusual four–point scaffold for organization of recognition functionality provided by eighteen–electron, cyclobutadiene based, cobalt metallocenes is of value.

Condensation of four equivalents of benzylamine with a tetra–formyl cobalt metallocene proceeds smoothly to afford the corresponding tetraimine. This, and related, reactions are performed under conditions of water removal to drive formation of the fully condensed product. The intention from this point forward is to induce exchange of the imine components via the preferential inclusion of alternative primary amines (in the form of imines) in the overall structure. Dynamic chemistry of this kind can take advantage of thermodynamic preferences for particular structures to drive a process of chemical evolution that selects for, in a given context, an energy minimized structure. It was the overall intent of this work to design systems, ultimately, for simple carbohydrate (monosaccharide binding), but our approach to this goal necessitated an incremental study where the exchange (evolution) of model systems was fully understood before advancing to the more complex structural problem of sugar binding. Accordingly, and to date, we have focussed our efforts on understanding exchange within a severely constrained system, one in which the guest (a metal ion) would be indiscriminate, though effective, in its binding, and where only a single additional amine would be present as a competitive imine forming species. Results from these recent experiments are encouraging, thought as yet far from definitive: spectroscopic evidence for replacement of benzylamine with 2–aminomethylpyridine has been obtained and this exchange appears to be enhanced in the presence of excess zinc ion (the intention being to favor the possible ion–binding pocket formed by a organized cluster of pyridyl nitrogen binding sites). However, such evidence is at present NMR based and these experiments await our development of an HPLC protocol for quantitative analysis. When this work is complete we should have a clear picture of the behavior of this model system, be well positioned to design second generation systems, and envisage the next steps in an incremental approach to the project's final goal.