Azirine Weinreb amides: Preparation and use in the synthesis of 2-acylated aziridines and azirines

• Published in: Tetrahedron Vol. 167; p. 134255
• Main Authors: Prokop'eva, Irina N., Tomashenko, Olesya A., Matveeva, Daria R., Galenko, Ekaterina E., Novikov, Mikhail S., Khlebnikov, Alexander F.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 07-11-2024
• Subjects: Aziridines; Azirines; Organometallic compounds; Reduction; Weinreb amides; Weinreb amides; Reduction; Aziridines; Azirines; Organometallic compounds
• ISSN: 0040-4020
• DOI: 10.1016/j.tet.2024.134255

Azirine Weinreb amides (N-methoxy-N-methyl-2H-azirine-2-carboxamides) were synthesized in yields of 35–94 % by the reaction of N,O-dimethylhydroxylamine with 2H-azirine-2-carbonyl chlorides, formed by the catalytic isomerization of 5-chloroisoxazoles. Red-Al reduction of azirine Weinreb amides affects only the azirine CN bond and leaves the C(O)NMeOMe group unaffected, forming stereoselectively 1-unprotected 3-substituted cis-N-methoxy-N-methylaziridine-2-carboxamides. The developed approach is a stereo-complementary addition to the previously proposed method for preparing unprotected trans-N-methoxy-N-methyl-3-phenylaziridine-2-carboxamide. The Weinreb amide group in the synthesized cis-N-methoxy-N-methylaziridine-2-carboxamides was used to prepare cis-2-acyl-3-arylaziridines by reaction with organometallic compounds. The reaction of organomagnesium compounds with azirine Weinreb amides allow the stereoselective preparation of 3-aryl-3-aryl/hetary/alkyl-N-methoxy-N-methylaziridine-2-carboxamides; which, in turn, were used to obtain the corresponding aziridinyl ketones. The reaction of azirine Weinreb amides with bulky substituents in the 3-position of azirine with organometallic compounds occurs only at the C(O)NMeOMe group with retention of the azirine CN bond with the formation of 2-acyl-2H-azirines.
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•Synthesis of azirine Weinreb amides.•Red-Al reduction of azirine Weinreb amides affects only the azirine CN bond.•Stereoselective approach to 1-unprotected cis-N-MeO-N-Me-aziridine-2-carboxamides.•Preparation of cis-2-acyl-3-arylaziridines and 2-acyl-2H-azirines.•Stereoselective synthesis of 2-acyl-3-aryl-3-aryl/hetary/alkylaziridines.