Squaramide-Catalyzed Asymmetric aza-Friedel-Crafts/N,O-Acetalization Domino Reactions Between 2-Naphthols and Pyrazolinone Ketimines.

Abstract

N-Boc ketimines derived from pyrazolin-5-ones were explored to develop an unprecedented domino aza-Friedel-Crafts/N,O-acetalization reaction with 2-naphthols. The novel method requires a catalyst loading of only 0.5 mol % of a bifunctional squaramide catalyst, is scalable to gram amounts, and provides a new series of furanonaphthopyrazolidinone derivatives bearing two vicinal tetra-substituted stereogenic centers in excellent yields (95-98 %) and stereoselectivity (>99:1 d.r. and 97-98 % ee). A different reactivity was observed in the case of 1-naphthols and other electron-rich phenols, which led to the aza-Friedel-Crafts adducts in 70-98 % yield and 47-98 % ee.