A transition-metal-free multicomponent reaction towards constructing chiral 2H-1,4-benzoxazine scaffolds

Herein, a transition-metal-free multicomponent cascade reaction of readily available alpha-halogenated ketones, ortho-aminophenols, and aldehydes using a novel dipeptide-based phosphonium salt catalyst was developed for the efficient construction of various 2H-1,4-benzoxazine derivatives with excellent functional-group tolerance. The method represents an unprecedented approach for trapping active 1,5-bifunctional intermediates with alpha-halogenated ketones to access biologically important benzoxazine scaffolds bearing two stereogenic centers with excellent asymmetric induction.