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 C[dbnd]N 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 C[dbnd]N bond with the formation of 2-acyl-2H-azirines. © 2024 Elsevier Ltd
Original languageEnglish
JournalTetrahedron
Volume167
DOIs
StatePublished - 1 Nov 2024

    Research areas

  • Aziridines, Azirines, Organometallic compounds, Reduction, Weinreb amides, 2 acyl 3 arylaziridine, 2h azirine 2 carbonyl chloride, 3 (2,5 dimethylphenyl) n methoxy n methyl 2h azirine 2 carboxamide, 3 (2,5 dimethylphenyl)isoxazol 5(4h) one, 3 (4 bromophenyl) n methoxy n methyl 2h azirine 2 carboxamide, 3 (4 chlorophenyl) n methoxy n methyl 2h azirine 2 carboxamide, 3 (4 fluorophenyl) n methoxy n methyl 2h azirine 2 carboxamide, 3 (adamantan 1 yl) n methoxy n methyl 2h azirine 2 carboxamide, 3 (benzo[b]thiophen 2 yl) n methoxy n methyl 2h azirine 2 carboxamide, 3 (tert butyl) n methoxy n methyl 2h azirine 2 carboxamide, 3 ethyl n methoxy n methyl 2 phenyl 2h azirine 2 carboxamide, 3 substituted cis n methoxy n methylaziridine 2 carboxamide, 5 chloro 3 (2,5 dimethylphenyl)isoxazole, 5 chloro 3 ethyl 4 phenylisoxazole, 5 chloro 4 phenyl 3 (p tolyl)isoxazole, amide, azirine derivative, magnesium, n methoxy 3 (4 methoxyphenyl) n methyl 2h azirine 2 carboxamide, n methoxy n methyl 2 phenyl 3 (p tolyl) 2h azirine 2 carboxamide, n methoxy n methyl 2h azirine 2 carboxamide, n methoxy n methyl 3 (naphthalen 2 yl) 2h azirine 2 carboxamide, n methoxy n methyl 3 (p tolyl) 2h azirine 2 carboxamide, n methoxy n methyl 3 (thiophen 2 yl) 2h azirine 2 carboxamide, n methoxy n methyl 3 phenyl 2h azirine 2 carboxamide, n methoxy n methyl 3 phenylaziridine 2 carboxamide, organometallic compound, unclassified drug, acylation, Article, carbon nuclear magnetic resonance, chemical reaction, chemical structure, column chromatography, controlled study, crystallization, cyclization, drug synthesis, infrared spectroscopy, isomerization, proton nuclear magnetic resonance, stereoselectivity, X ray diffraction

ID: 126353636