Sc(OTf)₃‐Catalyzed Dearomative [3+2] Annulation of 5‐Aminoisoxazoles with Quinone Imine Ketals or Quinone Monoacetals

Abstract

Isoxazolines are highly significant for the development of new synthetic methodology and pharmaceutics. Indolines and 2,3dihydrobenzofurans are also privileged structures in natural products and pharmaceuticals. In continuation of our ongoing research on transformations of 5-aminoisoxazoles and quinone derivaties, herein we report Sc(OTf) 3 -catalyzed dearomative [3 + 2] annulations of 5-aminoisoxazoles with quinone imine ketals (QIKs) and quinone monoacetals (QMAs). A variety of indolineand 2,3-dihydrobenzofuran-fused isoxazolines were afforded in moderate to good yields with excellent diastereoselectivities (all cases > 20 : 1 dr). This method featured mild reaction conditions, wide substrate scope, and gram-scale synthesis.

Asymmetric Synthesis of Bicyclic Isoxazolines via Dearomative Cycloaddition of 4-Nitroisoxazoles with Zwitterionic π-Allyl Palladium Species

“…reported Diels–Alder reactions of 4-nitroisoxazoles with dienes VI to give bicyclic products as racemates . In fact, enantioselective transformation is currently limited to the chiral phosphoric acid-catalyzed annulation of 5-aminoisoxazoles with quinone monoimines VII , as reported by Zhang et al We have been working on the direct functionalization of heterocycles, particularly isoxazoles . In this paper, we report the dearomative cycloadditions of 4-nitroisoxazoles with catalytically generated zwitterionic π-allyl palladium species. , The reactions proceeded in the presence of chiral ligands under mild conditions to produce optically active bicyclic isoxazolines that could not be reached by other means.…”

Design, Synthesis, Antifungal Activity, and Molecular Docking Studies of Novel Chiral Isoxazoline-Benzofuran-Sulfonamide Derivatives

“…The intermediate product 1g – 1o was obtained after purification by recrystallization from anhydrous ethanol (Scheme ). The substrates 2a – 2f were synthesized based on the reported literature. − …”

Recent Advances in the Domino Annulation Reaction of Quinone Imines

“…In 2022, Zhang et al also reported a Sc(OTf) 3 -catalyzed dearomative [3 + 2] annulation reaction involving QIK 5 and 5-amino-isoxazolines 169 , which led to the synthesis of a series of indoline-fused isoxazolines 170 in moderate to high yields with excellent diastereoselectivities ( Scheme 36 ) [ 90 ]. The reported reaction mechanism is similar to their previous findings.…”