The chemistry of calixarene-based copper complexes and anhydrides

Abstract

Calixarenes, cavity-containing macrocyclic compounds, if appropriately functionalized, can be potential enzyme mimics. Two goals have been pursued in this work. The first goal focuses on developing $\rm calix\lbrack 4\rbrack arene$-based mono- and dinuclear copper complexes that are intended to mimic the structures and reactivity of the active sites of copper proteins such as the monooxygenases tyrosinase and dopamine $\beta$-hydroxylase. The second goal focuses on developing a method for the introduction of difunctionality on the upper rim of calixarenes. Starting from mono- and $\rm dicyanomethylcalix\lbrack 4\rbrack arenes,$ a series of functionalized $\rm calix\lbrack 4\rbrack arenes$ carrying one or two ligand arms at the upper rim are prepared. Two kinds of ligand arms containing tridentate nitrogen donors are employed: one is $\rm bis\lbrack 2$-(3,5-dimethyl-1-pyrazoly)ethyl$\rbrack$amine (pyrazole series); the other is bis-$(2,2\sp\prime$-pyridylethyl)amine (pyridine series). Other functionalized $\rm calix\lbrack 4\rbrack arenes$ carrying two pyrazole-ligand arms at the lower rim are also prepared. The Cu(I) complexes of the pyrazole series show no tendency to activate molecular dioxygen. The Cu(II) complexes are also stable, in contrast to Nolte's observation with similar but non-calixarene derived compounds. Both mono- and dicopper(I) complexes of the pyridine series react with molecular dioxygen to produce dinuclear copper-dioxygen adducts. These decompose to oxygenated dicopper(II) complexes, in which selective ligand hydroxylation occurs at the benzylic position, providing a functional model of dopamine $\beta$-hydroxylase.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) The introduction of functionality into calixarenes continues to be one of the major goals in the rapidly expanding chemistry of these compounds. $\rm Calix\lbrack 4\rbrack arenes$ carrying two different functional groups on the upper rim have been synthesized by the reaction of nucleophiles with the bridged anhydride obtained from a $\rm calix\lbrack 4\rbrack arene$ carrying carboxymethyl groups at the 5 and 17-positions. Nucleophiles include alcohols (to give half esters) and amines, including $\alpha$-amino esters (to give optically active half amides). Further reaction of the remaining carboxyl function can be effected to give, for example, $\rm calix\lbrack 4\rbrack arenes$ carrying two amino ester moieties on the upper rim.(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)