Synthesis of Spirocyclic 1‐Pyrrolines from Nitrones and Arynes through a Dearomative [3,3′]‐Sigmatropic Rearrangement

Abstract

A dearomative [3,3′]‐sigmatropic rearrangement that converts N‐alkenylbenzisoxazolines into spirocyclic pyrroline cyclohexadienones has been developed by using the dipolar cycloaddition of an N‐alkenylnitrone and an aryne to access these unusual transient rearrangement precursors. This cascade reaction affords spirocyclic pyrrolines that are inaccessible through dipolar cycloadditions of exocyclic cyclohexenones and provides a fundamentally new approach to novel spirocyclic pyrroline and pyrrolidine motifs that are common scaffolds in biologically‐active molecules. Diastereoselective functionalization processes have also been explored to demonstrate the divergent synthetic utility of the unsaturated spirocyclic products.

Synthesis of Some novel Azomethine Oxide Derived from Aromatic Oximes and their Anti-microbial Studies

“…This reaction forms the N-O double bond and creates a stable nitronate intermediate, which can be isolated or used directly in subsequent reactions (Murahashi and Imada, 2019). One of the most notable characteristics of nitrones is their ability to undergo 1,3-dipolar cycloaddition reactions with alkenes or alkynes, known as the "nitrone-alkene/alkyne" cycloaddition (Yang, et al, 2017;Alshreimi, et al, 2020). This reaction forms isoxazolidine or isoxazole derivatives, depending on the specific conditions used (Qaddo and Abed, 2022;Li, et al, 2021).…”

Brønsted Acid Catalyzed Dearomatization by Intramolecular Hydroalkoxylation/Claisen Rearrangement: Diastereo‐ and Enantioselective Synthesis of Spirolactams

“…[1a,2] To date,s everal efficient strategies such as Birch reduction [3] and hydrogenation [4] have been established, but most of these methods inevitably use quantitative amounts of metals or noble metal catalysts or hash conditions to overcome the high resonance energy.A sac onsequence,i tis essential to develop viable alternative approaches.R ecently, [3,3]-sigmatropic rearrangements have been explored as am ild approach to dearomatize with quaternary carbon stereocenter installation. [5] In these cases,t ransition metals such as Pd, Cu, Au,a nd Ni have been typically employed to dearomatize the aromatic compounds including indoles, furans,and naphthol derivatives through aClaisen rearrangement. In 2015, an important breakthrough was achieved in this regard by List and co-workers,w ho disclosed an elegant chiral Brønsted acid (BA) catalyzed dearomatization of naphthyl hydrazines via aC laisen rearrangement (Scheme 1a).…”

“…In 2015, an important breakthrough was achieved in this regard by List and co-workers,w ho disclosed an elegant chiral Brønsted acid (BA) catalyzed dearomatization of naphthyl hydrazines via aC laisen rearrangement (Scheme 1a). [6a] This strategy was also extended to the synthesis of chiral 2H-a nd 3H-pyrroles via ad earomatizing Fischer indolization and an in situ [1,5]-alkyl shift by the same group. [6b] Despite these significant advances, [5,6] the substrate scopes of these reactions were still limited to heterocyclic aromatic compounds and activated arenes.Thus,the development of adearomatization of nonactivated arenes via a[3,3]sigmatropic rearrangement, especially in an enantioselective, atom-economic,a nd environmentally friendly way,i sh ighly desirable.…”