Chiral Pyrophosphoric Acid Catalysts for the para-Selective and Eanantioselective Aza-Friedel–Crafts Reaction of Phenols

Haruka Okamoto, Kohei Toh, Takuya Mochizuki, Hidefumi Nakatsuji, Akira Sakakura,* Manabu Hatano,* Kazuaki Ishihara* 
Synthesis2018, 50 (23), 4577–4590.  (Published online: Aug  22, 2018) 
DOI: 10.1055/s-0037-1610250 

Chiral BINOL-derived pyrophosphoric acid catalysts were developed and used for the regio- and enantioselective aza-Friedel–Crafts reaction of phenols with aldimines.  ortho/ para-Directing phenols could react at the para-position selectively with moderate to good enantioselectivities.  Moreover, the gram-scale transformation of a product into the key intermediate for the antifungal agent ( R)-bifonazole was demonstrated.