A three-component, general and practical route for diastereoselective synthesis of aza-spirocyclic pyrazolones via a decarboxylative annulation process

An efficient, general, and practical route for highly diastereoselective synthesis of aza-spirocyclic pyrazolones from easily available alpha-amino acids, aldehydes, and alkylidene pyrazolones by means of a decarboxylative annulation process is reported. This high-yielding reaction proceeds through a [3+2]-cycloaddition reaction between alkylidene pyrazolones and a nonstabilized azomethine ylide generated in situ. This method provides easy and smooth access to a variety of highly functionalized aza-spirocyclic pyrazolones in excellent yields (up to 96%). The obtained spiro-pyrazolones comprise four contiguous stereogenic centers including a quaternary carbon center.

Automated summary

This study presents an efficient and practical method for the synthesis of aza-spirocyclic pyrazolones from easily accessible starting materials. The high-yielding reaction involves a [3+2] cycloaddition between alkylidene pyrazolones and a nonstabilized azomethine ylide, resulting in excellent yields of highly functionalized products. The obtained spiro-pyrazolones contain four contiguous stereogenic centers, including a quaternary carbon center.