Enantioselective Synthesis of Isoxazoline N-Oxides via Pd-Catalyzed Asymmetric Allylic Cycloaddition of Nitro-Containing Allylic Carbonates

Abstract

A useful method for the enantioselective preparation of isoxazoline N-oxides via Pd-catalyzed asymmetric allylic cycloaddition of nitro-containing allylic carbonates has been developed. By using palladium complex in situ generated from Pd 2 (dba) 3 •CHCl 3 and phosphoramidite L2 as a catalyst under mild conditions, the transformation afforded vinylated isoxazoline N-oxides in high yields with acceptably high enantioselectivities.

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…The same authors also developed intramolecular cycloadditions of allylic carbonates ( 277 ) with a nitroalkyl substituent to yield isoxazoline N -oxides with high ee values (up to 91%; Scheme 290 ) using Pd/( S,S,S )- L11 . 717 …”

Pd‐Catalyzed Chemoselective Bis‐Allylic Substitution of Allylic Dicarbonates with Arylated Nitromethanes: A Route to 1,2‐Oxazine N‐Oxides

“…In 1992, Trost reported Pd‐catalyzed allylic substitution of cis ‐1,4 diacetoxycyclopent‐2‐ene with lithium [(phenylsulfonyl)methylene]nitronate through sequential C ‐ and O ‐nucleophilic attacks to afford isoxazoline N ‐oxide [5] . Most recently, we presented that Pd‐catalyzed allylic intramolecular cycloaddition of nitro‐containing allylic carbonates in which nitro‐group working as O ‐nucleophiles to afford isoxazoline N ‐oxides with high chemo‐, regio‐ and enantioselectivities [6] …”

“…[5] Most recently, we presented that Pd-catalyzed allylic intramolecular cycloaddition of nitro-containing allylic carbonates in which nitro-group working as O-nucleophiles to afford isoxazoline N-oxides with high chemo-, regio-and enantioselectivities. [6] Transition metal-catalyzed bis-allylic substitution of dual allylic donors with dual nucleophiles is a useful approach to construct structurally distinct cyclic compounds. [7] Allylic donors derived from 2-methylenepropane-1,3-diol are one of the most prevalent dual substrates for this type of transformation to construct various functionalized carbo-and heterocycles (Scheme 1a).…”

Five-Membered Hetarene N-Oxides: Recent Advances in Synthesis and Reactivity

“…From the structural point of view, isoxazoline N-oxides are cyclic nitronates which undergo common reduction to isoxazolines, 1,3-aminoalcohols, β-hydroxyketoximes and pyrrolidones. 21 Upon base treatment, isoxazoline N-oxides are easily converted to the corresponding isoxazoles. 10,11 Although the reaction has a broad substrate scope, there is an exception for several isoxazoline N-oxides bearing ester moiety at the C(5) position of the ring.…”

“…From a structural point of view, isoxazoline N-oxides are cyclic nitronates that undergo standard reductions to give isoxazolines, 1,3-aminoalcohols, -hydroxyketoximes and pyrrolidones. 21…”