Proline analogues, such as quaternary-based varieties, have an important role as modifiers of peptide conformation and bioactivity. They could be obtained through [1,2]-Stevens rearrangements upon the treatment of the related optically enriched cyclic ammonium salts with a base. Nevertheless, the ylides based on preformed ammonium salts required excessive base and were limited to <i>N</i>-substituents, and enantioselective [1,2]-rearrangement of achiral ammonium salts needed the inducing of chiral basic promoter. One the other hand, the generation of ammonium ylides from α-diazo carbonyls and tertiary amines largely expanded the application of such kind of rearrangement. The ring-expansion of azetidine derivatives with carbenoids provided an alternative route to construct proline derivatives. Inspired by the performance of α-diazo pyrazoleamides in forming chiral Lewis acid-bound ylide intermediates, we disclose a chiral cobalt-catalyzed asymmetric ring-expansion of ammonium ylides, generated from α-diazo pyrazoleamides and <i>N</i>-aryl-3-methyleneazetidines. A series of quaternary 4-methylene prolineamides were obtained in high yields with excellent enantioselectivities from readily available substrates and chiral catalyst.

Asymmetric catalytic ring-expansion of 3-methyleneazetidines with α-diazo pyrazoamides towards proline-derivatives

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