The use of coordinating moieties as directing groups for the functionalization of aromatic CH bonds has become an established tool to enhance reactivity and induce regioselectivity. Nevertheless, with regard to the synthetic applicability of CH activation, there is a growing interest in transformations in which the directing group can be fully abandoned, thus allowing the direct functionalization of simple benzene derivatives. However, this approach requires the disclosure of new strategies to achieve reactivity and to control selectivity. In this review, recent advances in the emerging field of non-chelate-assisted CH activation are discussed, highlighting some of the most intriguing and inspiring examples of induction of reactivity and selectivity.

Beyond directing groups: transition-metal-catalyzed C-H activation of simple arenes.

A bioinspired iron-based catalyst with semiconductor photocatalytic functions in combination with a high surface area holds promise for synthetic chemistry via combining photocatalysis with organosynthesis. Here exemplified for phenol synthesis, Fe-g-C3N4/SBA-15 is able to oxidize benzene to phenol with H2O2 even without the aid of strong acids or alkaline promoters. By taking advantage of both catalysis and photocatalyisis functions of g-C3N4 nanoparticles, the yield of the phenol can be markedly promoted.

Fe-g-C3N4-Catalyzed Oxidation of Benzene to Phenol Using Hydrogen Peroxide and Visible Light

Der Einsatz von koordinierenden Gruppen als dirigierende Gruppen ist eine zuverlassige Methode zur Kontrolle von Reaktivitat und Selektivitat bei der Aktivierung von Aryl-C-H-Bindungen. Im Hinblick auf die Anwendbarkeit von C-H-Aktivierungen in der Synthese besteht derzeit ein groses Interesse daran, Reaktionen zu entwickeln, in denen vollig auf dirigierende Gruppen verzichtet werden kann und somit die Funktionalisierung einfacher Benzolderivate moglich wird. Dieser Ansatz erfordert jedoch neue Strategien zur Reaktivitats- und Selektivitatskontrolle. In diesem Kurzaufsatz werden aktuelle Fortschritte in dem noch jungen Gebiet der nicht-chelatvermittelten C-H-Aktivierung diskutiert, wobei einige inspirierende Beispiele zur Reaktivitats- und Selektivitatsinduktion hervorgehoben werden.

Ohne dirigierende Gruppen: übergangsmetallkatalysierte C-H-Aktivierung einfacher Arene

The visible-light-induced photocatalytic conversion of aqueous benzene to phenol on Au-nanoparticle-supported layered titanate was accelerated when the reaction was conducted in the presence of aqueous phenol.

Efficient Visible-Light-Induced Photocatalytic Activity on Gold-Nanoparticle-Supported Layered Titanate

This review is a summary and critical analysis of recent advances in the understanding of (a) the nature and coordination state of Ti ions and other functional groups (such as OH) on dehydrated titanium silicate molecular sieves, (b) the type and structure of the oxo intermediates generated by the interaction of these active sites with oxidant/reactant molecules during catalytic reactions, and (c) the factors that influence the reactivity and selectivity of these active sites and reaction intermediates. In the dehydrated state, most of the Ti 4+ ions have the tetrapodal (Ti(OSi) 4 ) or the tripodal (Ti(OSi) 3 OH) structure. On contact with H 2 O 2 , titanium oxo species, Ti(O 2 H) and Ti(O 2 − ), respectively, are formed. On reaction with organic reactants, O–O bond cleavage in these titanium oxo species occurs in a hetero- or homolytic manner. Product selectivity is determined by the relative importance of these two modes of O–O cleavage. Factors such as the coordinative environment of titanium, substituents on the O–O bond (H or alkyl), temperature, solvent, nature of the organic reactant, etc. influence the mode of O–O cleavage. Correlations between the structure and catalytic activity of titanium sites and oxo-titanium intermediates are also described.

Active Sites and Reactive Intermediates in Titanium Silicate Molecular Sieves

Direct Oxidation of Benzene to Phenol with Hydrogen Peroxide over a Modified Titanium Silicalite

Immobilization of penicillin G acylase on aminoalkylated polyacrylic supports

The hydroxylation of a series of aromatic hydrocarbons with hydrogen peroxide, catalyzed by iron complexes with pyrazine-3-carboxylic acid N-oxide, was investigated, operating in a biphasic reaction medium.

The new catalyst showed a high selectivity to the corresponding phenols, minimizing the over-oxidation reactions to polyoxygenated derivatives and tars which, along with dimers formation, are the major limitations of the classical Fenton’s reagent for a practical synthetic application.

In the case of alkylbenzenes, the competitive side chain oxidation at the benzylic positions also occurred. Electron rich substrates, such as anisole, were oxidized with very poor selectivity.

The reactions were carried out in a biphasic system that allows a convenient recovery and recycling of the catalyst by phase separation techniques. The catalyst showed a complete retention of activity after six consecutive reaction cycles.

The new catalyst appears as a promising tool for the direct synthesis of phenols, in alternative to the conventional multi-step methods.

Direct synthesis of phenols by iron-catalyzed biphasic oxidation of aromatic hydrocarbons with hydrogen peroxide

Immobilization of d-amino acid oxidase from different yeasts: Characterization and application in the deamination of cephalosporin C

The hydroxylation of benzene and toluene with hydrogen peroxide, catalysed by iron complexes with nitrogen ligands in a biphasic reaction medium, was investigated. After testing a series of pyridine and pyrazinecarboxylic acid derivatives, it was found that the ligand markedly affects the catalyst efficiency and the selectivity based on the oxidant. In the case of toluene, the ligand has a tuning effect on the catalyst activity, driving the oxidation preferentially to the ring or to the methyl group. The complex with pyrazine-3-carboxylic acid N -oxide was selected as the most efficient catalyst and appears to be a promising tool for the direct synthesis of phenols. The mechanism of the aromatic hydroxylation is also discussed, in comparison with the conventional Fenton’s reagent.

Daniele Bianchi

Papers

Direct Oxidation of Benzene to Phenol with Hydrogen Peroxide over a Modified Titanium Silicalite

Immobilization of penicillin G acylase on aminoalkylated polyacrylic supports

Direct synthesis of phenols by iron-catalyzed biphasic oxidation of aromatic hydrocarbons with hydrogen peroxide

Immobilization of d-amino acid oxidase from different yeasts: Characterization and application in the deamination of cephalosporin C

Ligand effect on the iron-catalysed biphasic oxidation of aromatic hydrocarbons by hydrogen peroxide