Electrophilic aromatic substitution of azines catalysed by Frustrated Lewis pairs

Azines are nitrogen-containing aromatic rings of utmost synthetic relevance in natural products, pharmaceuticals, agrochemicals and materials science.

Although nucleophilic aromatic substitution techniques are routine, these methods require air-sensitive and highly reactive nucleophiles, in most instances organometallic reagents.

In sharp contrast, electrophilic aromatic substitutions are particularly difficult to the electron-poor nature of the azines, inevitably requiring harsh reaction conditions.

Taking into consideration the wider availability of electrophilic partners when compared to their corresponding nucleophilic congerener, the development of a catalytic technique aimed at providing a mild, chemoselective and site-selective electrophilic aromatic substitution of azines will have tremendous consequences for the praxis of heterocyclic chemistry, particularly in late-stage applications.

Aimed at providing a solution to such goal, LEWIS-PYR will design a conceptually new platform to activate unbiased azines via electrophilic aromatic substitution by using frustrated Lewis Pairs (FLPs) as a polarity inversion vehicles, allowing to substitute a series of a priori electron-poor nitrogen-containing electrocycles with a wide variety of different electrophilic partners.