Chiral Spirophosphoric-Acid-Catalyzed Divergent Vinylogous Mannich and -Friedel-Crafts Reactions of 2-Methoxyfuran.

The first enantioselective vinylogous Mannich reaction is developed using 2-methoxyfuran under chiral spirophosphoric acid catalysis. The strategy involves 4-isoxazoline derivatives as cyclic ketimine surrogates and provides γ-butenolide scaffolds (up to 97% ee and >20:1 dr). The mechanistic investigations suggest that an generated water molecule plays a crucial role in delivering γ-butenolide, while the use of molecular sieves delivers -Friedel-Crafts products.