Organocatalytic Enantioselective Vinylogous Aldol Reaction of 5-Alkyl-4-Nitroisoxazoles to Paraformaldehyde.

An organocatalytic asymmetric aldol reaction of 5-alkyl-4-nitroisoxazoles to paraformaldehyde has been developed. By using a chiral dipeptide-based urea-amide-guanidinium as the phase-transfer catalyst, the transformations were promoted by sodium acetate, leading to a range of enantio-enriched isoxazole derivatives in high yields with moderate to excellent enantioselectivities. This work represents the first example of constructing chiral C-C bonds at the α-position of 5-alkyl-4-nitroisoxazoles. The viability of readily accessing chiral fungicides from the obtained aldol products demonstrates the important utility of this method.