Mannich Cyclization of Bifunctional Hydroxylamines by Aza‐Kornblum–DeLaMare Rearrangement to Form Cyclopentyl β‐Amino Esters

We report that readily accessible N ‐haloalkyl hydroxylamines serve as bifunctional imine surrogates for novel (4 + 1) Mannich cyclizations with β ‐keto esters under mild phase‐transfer catalytic conditions. This method affords a series of cyclopentyl β ‐amino esters bearing adjacent quaternary and tertiary carbon centers in good yields. Notably, the diastereomeric products are separable by silica gel chromatography under achiral tetrabutylammonium bromide (TBAB) catalysis, enabling the streamlined synthesis of both pure trans ‐ and cis ‐derivatives in a single operation. Furthermore, by employing a chiral phase‐transfer catalyst, the reaction delivers the corresponding chiral products with high enantioselectivity and diastereoselectivity (up to 92% ee, >20:1 dr). Mechanistic studies reveal that the cyclization proceeds via a distinctive cascade involving C ‐alkylation, aza‐Kornblum–DeLaMare rearrangement, and ring‐closing Mannich reaction.