Involvement of azomethine ylides in the thermal rearrangement of aziridinyl ketones to pyrroles

Oxiranyl Anions and Aziridinyl Anions

“…Padwa reported that heating trans -aziridinyl ketone 302 in deuteriomethanol at 77 °C led to the formation of cis -aziridinyl ketone having a deuterium atom on the aziridine ring 303 (Scheme ) . A similar study was carried out by Cromwell …”

The Baldwin Rearrangement: Synthesis of 2‐Acylaziridines

“…Thermolysis of 2‐acylaziridines (sometimes under the conditions of their formation) can take place through azomethine ylide formation to produce 4‐oxazolines (see Scheme ), pyrroles, enamines or carbonyl compounds as a myriad of side products , . The isomerization of 2‐acylaziridines into azomethine ylides can be retarded by various factors such as the steric hindrance or electronic properties of their N ‐substituents . The presence of a bridgehead ring system in the α‐position to the nitrogen atom (see isoxazoline 26 ) hampers the isomerization of 2‐acylaziridines and allows their isolation in good yields .…”

“…[35] After these seminal studies, several groups described 4-substituted isoxazoline rearrangements under thermal conditions and found that the efficiency of formation and the stability of 2-acylaziridines depend significantly on the nature of their substituents (Scheme 4). [38][39][40][41][42][43] Thermolysis of 2-acylaziridines (sometimes under the conditions of their formation) can take place through azomethine ylide formation to produce 4-oxazolines (see Scheme 2), pyrroles, enamines or carbonyl compounds as a myriad of side products. [19,20] The isomerization of 2-acylaziridines into azomethine ylides can be retarded by various factors such as the steric hindrance or electronic properties of their N-substituents.…”

“…[19,20] The isomerization of 2-acylaziridines into azomethine ylides can be retarded by various factors such as the steric hindrance or electronic properties of their N-substituents. [39] The presence of a bridgehead ring system in the α-position to the nitrogen atom (see isoxazoline 26) hampers the isomerization of 2-acylaziridines and allows their isolation in good yields. [43] In general, 4-isoxazolines bearing aryl groups at C-5 are converted into 2-acylaziridines in better yields than those substituted with alkyl groups at C-5.…”

The Synthesis of the Pyrrole Ring

“…(250) The facile cleavage of the isoxazole ring has been utilized in several pyrrole syntheses. (254) Hydrolysis and ring rearrangement of the Diels-Alder adduct formed from maleic anhydride and 4-methyl-5-propoxyoxazole in acidic media yield 2-acetylpyrrole-3,4-dicarboxylic acid. (252a ' b) It is thought that the latter reaction proceeds via the intermediate acylaziridine (D62), but the isolation of the pyrrole carboxylic esters (D66) and (D67) in a 5 : 1 ratio from AMsoxazoline (D65) indicates that an alternative [3,3] sigmatropic rearrangement (D68) ->(D69) may be operating.…”