Silane-mediated, facile C-H and N-H methylation using formaldehyde.

The use of ( para )-formaldehyde for the methylation/alkylation of C(sp 2 )-H and N-H bonds, utilizing a combination of silane and hexafluoroisopropanol (HFIP) as activators, is reported. Overcoming the complexity of C(sp 2 )-H methylation on aryl and indole substrates, the process utilizes a Friedel-Crafts alkylation, followed by silane as a hydride donor, under a mild acidic medium. The method has been employed for the synthesis of the antifungal drug butenafine and a derivative of the non-steroidal anti-inflammatory drug (NSAID) flurbiprofen.