Development of a Kilogram-Scale Chemical Process for a Chiral Spirocyclic Isoxazolone

A short and scalable process for the facile synthesis of chiral spirocyclic isoxazolone 1 was developed and demonstrated on a multiple kilogram scale in four steps from a readily available starting material 8. To achieve process sustainability and efficiency, we implemented a highly efficient catalytic asymmetric allylic alkylation and a telescopic chemical process. More than 160 kg of the spirocyclic isoxazolone 1 were produced as a crystalline solid by a simple operation with >99:1 er and 38% overall yield. The structure of 1 was further confirmed by single-crystal X-ray analysis.