Enantiomerically pure 2-aryl(alkyl)-2-trifluoromethylaziridines: synthesis and ring opening with selected O- and N-nucleophiles

Abstract

We report herein the synthesis of enantiomerically pure 2-phenyl- and 2-ethyl-2-trifluoromethylaziridines by Mitsunobu-type cyclisation of the corresponding N-protected amino alcohols, and our results regarding their ring opening with selected nucleophiles. Under basic conditions, N-tosyl aziridines have been regioselectively opened at the less hindered carbon. Under acidic conditions, the regioselectivity of the attack depends on the nature of the substituent at C-2 and on the nitrogen protecting group.

Synthesis of Fluoro‐, Monofluoromethyl‐, Difluoromethyl‐, and Trifluoromethyl‐Substituted Three‐Membered Rings

“…Aziridines were produced in good yields except for the aziridine 131 c , which was obtained alongside a piperazine heterocycle, probably resulting from an intermolecular reaction rather than the expected intramolecular cyclization of the intermediate. At the same time, Grellepois [67] et al. reported a similar strategy to obtain enantiopure trifluoromethyl aziridine.…”

Catalytic Enantioselective Aza‐Benzoin Reactions of Aldehydes with 2H‐Azirines

“…[21] In contrast, the transformation of the tosylated aziridine intermediate 7,prepared from 3a,led to the b-amino-a-hydroxyketone 8 (Scheme 3c). [22,23] In summary,wehave successfully developed anew NHCcatalyzed aza-benzoin reaction of aldehydes with 2H-azirines, thus paving the way for synthetic chemists to build various chiral aziridines in high yields with excellent enantioselectiv-ities.This new protocol allows the rapid assembly of optically active aziridines from simple and readily available starting materials under mild reaction conditions.F urther investigations on 2H-azirines as starting materials in asymmetric synthesis,aswell as adetailed mechanistic study,are currently underway in our laboratory.…”

Catalytic Enantioselective Aza‐Benzoin Reactions of Aldehydes with 2H‐Azirines

“…The reaction of 3 c with hydrogen chloride in THF gave the β‐chloro‐α‐aminoketone 6 in good yield (Scheme b) . In contrast, the transformation of the tosylated aziridine intermediate 7 , prepared from 3 a , led to the β‐amino‐α‐hydroxyketone 8 (Scheme c) …”