Template catalysis via non-transition metal complexes. New highly selective syntheses on phenol systems

A methodological approach to conventional phenol chemistry based on the concepts and achievements of modern coordination chemistry allowed to find specific conditions for improving classical reactions and discovering new selective processes. Substrates, reagents, and ligands could be organized around non transition metal cations in suitable complexes, which were able to control the reactions and to determine highly selective ortho—attack on phenol systems. Template reactions of phenol substrates with carbonyl compounds in the presence of suitable ligands led to new general processes of ortho—formylation, ortho—acylation, ortho—alkylation and allylation. A rational route to all—ortho regular novolac resins was also disclosed. By using the basic strategy of Ziegler—Natta catalysis, the first synthesis of isotactic and syndiotactic all—ortho ethylidene—linked polyphenols was performed. Other synthetically useful Friedel—Crafts processes were performed according to an intramolecular template mechanism leading to new syntheses of important classes of oxygen heterocycles such as flavenes, chromanes, benzofuran derivatives, benzodioxins, and benzopyrylium salts. STRATEGY Activation of phenols, enols and indoles, which are typical ambident nucleophilic systems, is traditionally achieved by using strong bases which convert the substrates into the corresponding anions (phenolate, enolate, etc.), along with the use of dipolar aprotic solvents of high donicity (1) or phase transfer catalysis (2). In these conditions, the negative influence of the cation on reactivity is strongly reduced and, as a consequence, high activation of the substrate is usually observed. Moreover, predominant or exclusive functionalization at the more negative center (0, N) of the ambident system occurs (3). Reversing this general synthetic strategy, some years ago we focused our attention on the possible positive role of the cation and looked at these reactions in terms of coordinated processes in self—organized systems rather than of anion activation only (4). As far as phenol chemistry is concerned, we studied the possibility to exploit the complex structures of phenol salts as self—catalyzing systems, thereby systematically changing their organization in order to control and diversify their reactivity. In this systems the cation can play a fundamental role in coordinating both the phenolic substrate and the reagent, inducing intramolecular irreversible reactions within the phenolate—reagent complex. In order to achieve this goal the following rules are strictly required: i) the structure of the salt has to be designed according to the reagent or, viceversa, the reagent has to be selected in order to chelate the cation; ii) solvent and any species present in the reaction medium must not exclude the reagent from complexation in the reactive structure of the salt. On these bases a systematic research on phenol salts of highly coordinating non—transition metals was undertaken, utilizing mainly salts of lithium, magnesium, zinc, titanium, etc., in aprotic non polar media. Initially we selected as reagents carbonyl compounds and their oxygen derivatives according to their known complexing ability towards the aforementioned hard cations.

Field of study: Chemistry