Photochemical Conversion of Isoxazoles to 5-Hydroxyimidazolines

Abstract

Photochemical conversion of isoxazole I to 5-hydroxyimidazoline VII proceeded via the trapping of the photogenerated acylazirine III with amines under UV light irradiation. This is the first report of the efficient synthesis of 5-hydroxyimidazolines that are not readily accessible by other means. 5-Hydroxyimidazolines were also converted into multisubstituted imidazoles in one step by treatment with trifluoroacetic anhydride (TFAA) and 2,6-lutidine in dichloromethane.

Recent updates on vinyl cyclopropanes, aziridines and oxiranes: access to heterocyclic scaffolds

“…Among various strategies employed to access isoxazolines, the dearomative cycloaddition of oxazoles and dienes has emerged as a potent and promising approach. 71 In 2023, Nakamura and collaborators 72 reported a methodology via a dearomative [3 + 2] cycloaddition reaction between 4-nitroisoxazoles 99 with diverse Pd-π-allyl 1,3-dipolar intermediates, resulting in the formation of bicyclic isoxazolines 101/102 (Scheme 33). The initial study commenced by treating isooxazolines 99 and vinyl carbonates 100 in the presence of Pd 2 dba 3 and phosphoramidite ligand (S)-DTBM-SEGPHOS L21, which furnished desired products 101/101′ in a moderate-to-excellent yield (up to 99%) with excellent enantioselectivity (up to 99% ee), albeit with poor diastereoselectivity (dr 1.4 : 1).…”

“…Various p-QMs with proximal ortho-hydroxyl groups underwent smooth [4 + 3] cycloaddition with vinyl aziridines 56 to accomplish an array of benoxazepines 105 in a good yield (up to 96%) and Scheme 33 Synthesis of isoxazolines by Nakamura's approach. 72 Scheme 34 Synthesis of [5,5] spirocycles by Trost's approach. 73…”

Strain Release Chemistry of Photogenerated Small‐Ring Intermediates

“…Mechanistically, the primary amine adds to the C=N double bond of the photogenerated 2‐acylazirine forming aziridine 121 , which readily undergoes ring‐opening and isomerization to ketone 122 . Cyclization and tautomerization finally yield in the 5‐hydroxyimidazoline derivatives 118 [42] …”