Enantioselective aza-Friedel–Crafts reaction of furan with α-ketimino esters induced by a conjugated double hydrogen bond network of chiral bis(phosphoric acid) catalysts

Abstract

Chiral C₂- and C₁-symmetric BINOL-derived bis(phosphoric acid) catalysts, which have OP(O)(OH)₂/OP(O)(OH)(OR) moieties at the 2,2′-positions, were developed and used for the enantioselective aza-Friedel–Crafts reaction of 2-methoxyfuran with α-ketimino esters for the first time. The intramolecular conjugated double hydrogen bond network is a key to increasing the Brønsted acidity and preventing deactivation of the catalysts. Highly functionalized α-amino acid derivatives with a chiral quaternary carbon center could be transformed into versatile optically active N- and O-heterocycles and an α-aryl-substituted serine.