General Asymmetric Synthesis of Densely Functionalized Pyrrolidines via Endo -Selective [3+2] Cycloaddition of β-Quaternary-Substituted Nitroalkenes and Azomethine Ylides.

A scalable endo -selective synthesis of 2,3,4,5-tetrasubstituted pyrrolidines via cycloaddition of nitroalkenes and azomethine ylides is reported using a P,N-type ferrocenyl ligand and [Cu(OTf)] ₂ ·C ₆ H ₆ . The robust method is tolerant of a wide range of functionalities, including rarely reported quaternary nitroalkene substitution and heteroaromatic and hindered ortho -substituted arenes on the azomethine ylide. Subsequent transformations highlight the utility of the method in the synthesis of densely functionalized small molecules suitable for fragment-based drug discovery and the cystic fibrosis C2-corrector clinical candidate ABBV-3221.