Efficient Access to Chiral Trisubstituted Aziridines via Catalytic Enantioselective Aza‐Darzens Reactions

Herein, we report a Zn‐ProPhenol catalyzed aza‐Darzens reaction using chlorinated aromatic ketones as nucleophilic partners for the efficient and enantioselective construction of complex trisubstituted aziridines. The α‐chloro‐β‐aminoketone intermediates featuring a chlorinated tetrasubstituted stereocenter can be isolated in high yields and selectivities for further derivatization. Alternatively, they can be directly transformed to the corresponding aziridines in a one‐pot fashion. Of note, the reaction can be run on gram‐scale with low catalyst loading without impacting its efficiency. Moreover, this methodology was extended to α‐bromoketones which are scarcely used in enantioselective catalysis because of their sensitivity and lack of accessibility. A Zn‐ProPhenol catalyzed aza‐Darzens reaction using α‐chloroketones allows the efficient construction of challenging trisubstituted aziridines with high enantio‐ and diastereoselectivities (up to 98 % ee, >20:1 d.r.). This method also provides an efficient access to complex chlorinated molecules featuring a tertiary stereogenic chloride.