Interrupted Curtius Rearrangements of Quaternary Proline Derivatives: A Flow Route to Acyclic Ketones and Unsaturated Pyrrolidines

In collaboration with UCD, we report a novel reaction pathway for quaternary N-Boc proline species under thermal Curtius rearrangement conditions through a continuous flow protocol. Fragmentation of the intermediate isocyanate species renders a proposed N-acyliminium species, which facilitates ring-opening by adventitious water to give γ-amino ketone products in the case of small aliphatic substituents, whereas benzylic appendages render unsaturated pyrrolidines via tautomerization of this proposed N-acyliminium intermediate.

Interrupted Curtius Rearrangements of Quaternary Proline Derivatives: A Flow Route to Acyclic Ketones and Unsaturated Pyrrolidines, Marcus Baumann, Thomas S. Moody, Megan Smyth and Scott Wharry, J. Org. Chem., 2021, doi: 10.1021/acs.joc.1c01133