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

摘要

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 0.5mol% 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.