Chemoselective Switch in the Asymmetric Organocatalysis of 5H‐Oxazol‐4‐ones and N‐Itaconimides: Addition–Protonation or [4+2] Cycloaddition

Abstract

AbstractWe report a synthetic strategy for a chemoselective switch and a diastereo‐divergent approach for the asymmetric reaction of 5H‐oxazol‐4‐ones and N‐itaconimides catalyzed by l‐tert‐leucine‐derived tertiary amine–urea compounds. The reaction was modulated to harness either tandem conjugate addition–protonation or [4+2] cycloaddition as major product with excellent enantio‐ and diastereoselectivities. Subjecting the enantio‐enriched cycloaddition products to a basic silica gel reagent yields the diastereomer vis‐à‐vis the product directly obtained under conditions for addition–protonation, thus opening a diastereo‐divergent route for creating 1,3‐tertiary‐hetero‐quaternary stereocenters. Quantum chemical studies further provide stereochemical analysis for the [4+2] process and a plausible mechanism for this chemoselective switch is proposed.