TY - JOUR

T1 - Azirine Weinreb amides: Preparation and use in the synthesis of 2-acylated aziridines and azirines

AU - Prokop'eva, I.N.

AU - Tomashenko, O.A.

AU - Matveeva, D.R.

AU - Galenko, E.E.

AU - Novikov, M.S.

AU - Khlebnikov, A.F.

N1 - Export Date: 19 October 2024 CODEN: TETRA Адрес для корреспонденции: Khlebnikov, A.F.; Saint Petersburg State University, 7/9 Universitetskaya nab., Russian Federation; эл. почта: a.khlebnikov@spbu.ru Химические вещества/CAS: amide, 17655-31-1; magnesium, 7439-95-4 Фирменные наименования: Bruker Avance 400, Bruker, United States Производители: Bruker, United States Сведения о финансировании: Saint Petersburg State University, SPbU Сведения о финансировании: Russian Science Foundation, RSF, 22-13-00011 Сведения о финансировании: Russian Science Foundation, RSF Текст о финансировании 1: In commemoration of the 300th anniversary of St Petersburg State University's founding. The authors gratefully acknowledge the financial support of Russian Science Foundation Project 22-13-00011. This research was carried out using resources of the Centre for Magnetic Resonance, the Research Centre for X-ray Diffraction Studies, the Centre for Chemical Analysis and Materials, and the Computer Centre of the Science Park of St. Petersburg State University. heterocycles. Текст о финансировании 2: The authors gratefully acknowledge the financial support of Russian Science Foundation Project 22-13-00011. This research was carried out using resources of the Centre for Magnetic Resonance, the Research Centre for X-ray Diffraction Studies, the Centre for Chemical Analysis and Materials, and the Computer Centre of the Science Park of St. Petersburg State University.

PY - 2024/11/1

Y1 - 2024/11/1

N2 - 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

AB - 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

KW - Aziridines

KW - Azirines

KW - Organometallic compounds

KW - Reduction

KW - Weinreb amides

KW - 2 acyl 3 arylaziridine

KW - 2h azirine 2 carbonyl chloride

KW - 3 (2,5 dimethylphenyl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 (2,5 dimethylphenyl)isoxazol 5(4h) one

KW - 3 (4 bromophenyl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 (4 chlorophenyl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 (4 fluorophenyl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 (adamantan 1 yl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 (benzo[b]thiophen 2 yl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 (tert butyl) n methoxy n methyl 2h azirine 2 carboxamide

KW - 3 ethyl n methoxy n methyl 2 phenyl 2h azirine 2 carboxamide

KW - 3 substituted cis n methoxy n methylaziridine 2 carboxamide

KW - 5 chloro 3 (2,5 dimethylphenyl)isoxazole

KW - 5 chloro 3 ethyl 4 phenylisoxazole

KW - 5 chloro 4 phenyl 3 (p tolyl)isoxazole

KW - amide

KW - azirine derivative

KW - magnesium

KW - n methoxy 3 (4 methoxyphenyl) n methyl 2h azirine 2 carboxamide

KW - n methoxy n methyl 2 phenyl 3 (p tolyl) 2h azirine 2 carboxamide

KW - n methoxy n methyl 2h azirine 2 carboxamide

KW - n methoxy n methyl 3 (naphthalen 2 yl) 2h azirine 2 carboxamide

KW - n methoxy n methyl 3 (p tolyl) 2h azirine 2 carboxamide

KW - n methoxy n methyl 3 (thiophen 2 yl) 2h azirine 2 carboxamide

KW - n methoxy n methyl 3 phenyl 2h azirine 2 carboxamide

KW - n methoxy n methyl 3 phenylaziridine 2 carboxamide

KW - organometallic compound

KW - unclassified drug

KW - acylation

KW - Article

KW - carbon nuclear magnetic resonance

KW - chemical reaction

KW - chemical structure

KW - column chromatography

KW - controlled study

KW - crystallization

KW - cyclization

KW - drug synthesis

KW - infrared spectroscopy

KW - isomerization

KW - proton nuclear magnetic resonance

KW - stereoselectivity

KW - X ray diffraction

UR - https://www.mendeley.com/catalogue/d4269bdc-af85-3b9c-87db-defc8df0af3f/

U2 - 10.1016/j.tet.2024.134255

DO - 10.1016/j.tet.2024.134255

M3 - статья

VL - 167

JO - Tetrahedron

JF - Tetrahedron

SN - 0040-4020

ER -