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

Abstract

Enantioselective dearomative cycloadditions of 4-nitroisoxazoles with vinylethylene carbonate (2) proceeded in the presence of Pd2(dba)3 and (S)-DTBM-SEGPHOS to give the corresponding bicyclic isoxazolines 3 and 4 in good to high yields with excellent enantioselectivities (≤99% ee). This synthetic approach could be applied to N-tosyl vinyl aziridine and 2-methylidenetrimethylene carbonate. Further transformations of the resulting cycloadducts 4a and 4i yielded not only its derivatives 10 and 11 but also the novel tetracyclic skeleton 12.

Pd-catalyzed oxa-[4 + n] dipolar cycloaddition using 1,4-O/C dipole synthons for the synthesis of O-heterocycles

“…Employing Segphos-type ligand (R)-L10 and a Pd(0) catalyst successfully delivered 28 in 94% yield with 77% ee (Scheme 8B). 18 A dearomatization process via Pd-catalyzed diastereoselective oxa-…”

“…Employing Segphos-type ligand ( R )- L10 and a Pd(0) catalyst successfully delivered 28 in 94% yield with 77% ee (Scheme 8B). 18…”

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).…”