The calixarene p-bromodienone route: from a chemical curiosity to an useful synthetic tool

Abstract

This review gives an account on the development of the calixarene “p-bromodienone route” which include the beginning of the story, the tested and potential applications, and a mention to a different strictly related procedure. The development of this route is due to the serendipitous discovery of calixarene derivatives containing the 4-tert-butyl-4-bromo-2,5-cyclohexadienone moiety (shortly, the p-bromodienone moiety). These derivatives undergo a silver-mediated nucleophilic substitution and a subsequent rearomatization to give products in which a nucleophilic agent is directly linked to the para-position of a calixarene aromatic ring in a sort of “aromatic ring umpolung”. The nucleophiles so far tested are O-nucleophiles (alcohols, phenols, carboxylates) or C-nucleophiles (activated aromatic rings, acetylides) which has led to the corresponding p-substituted derivatives or to unusual m-substituted calixarenes through an intermediate dienone-phenol rearrangement. In this way, a range of additional chemical functionalities can be attached to the calixarene scaffold which include interalia alkyno, carboxy, peptido and glyco substituents. On the basis of literature data, it can be expected that several additional nucleophiles, including S-, N-, and P-nucleophiles, could be used in the calixarene p-bromodienone route thus expanding its scope.