Regioselective Friedel-Crafts hydroalkylation using friendly conditions: Application to the synthesis of unsymmetrical triarylmethanes

Friedel-Crafts alkylation is one of the most important methods used in organic chemistry to create carbon-carbon bonds. The traditional conditions using alkyl halides activated by a Lewis or Brønsted acid has been widely described in the literature. Nevertheless, the Friedel-Crafts reaction using aldehydes or ketones as substrates, known as hydroxyalkylation, has been poorly described.

The development of regioselective Friedel-Crafts conditions is a challenge in organic synthesis. The growing interest in developing a “metal and solvent free" reactions justifies the particular attention that the Brønsted acids have received as an alternative to toxic and precious metals.

These last years the triarylmethanes attract considerable attention due to their applications in fine, medicinal and industrial chemistry. They have been used as protecting groups, dyes and or photochromic agents. They also showed interesting biological properties including anti-tumor and antioxidant activities. Different methods of preparation of symmetrical triarylmethanes have been described in the literature, nonetheless the synthesis of unsymmetrical ones has been very little explored.

In this work we describe an efficient regioselective method to prepare unsymmetrical triarylmethanes from enriched aromatic compounds, via a Friedel-Crafts hydroxyalkylation catalyzed by Brønsted acids using pyridylarylcarbinols as alkylating agents. The method described here is consistent with the principles of green chemistry and has significant advantages, such as the use of an inexpensive catalyst and the mild conditions. The method described is regioselective, offers a good yields, shorter reaction times and a possible extension to various substrates.