Ruthenium‐Catalyzed Direct Transformation of Alkenyl Oximes to 5‐Cyanated Isoxazolines: A Cascade Approach Based on Non‐Stabilized Radical Intermediate

Abstract

A ruthenium‐catalyzed ammoxidation of alkenyl oximes under mild and neutural condtions is described. In this method, tert‐butyl nitrite plays a dual role, acting as an oxidant as well as a nitrogen source. This reaction avoids using any toxic radical initiators or cyanide reagents. This convenient and practical method offers an easy access to 5‐cyanated isoxazolines in good to high yields, and shows good functional group tolerance and high efficiency. It is rather remarkable that this new reaction provides a strategically distinct approach based on non‐stabilized radical intermediate and constructs C–O and C≡N triple bonds in a single‐step. Moreover, the difunctionalization of unactivated olefins bearing oximes has been realized.

Radical Cascade Reactions of β,γ‐Unsaturated Hydrazones/Oximes

“…reported a radical‐based, mild and efficient cyanation method, which converted the alkenyl oxime to the cyanated isoxazolines without using any highly toxic cyanide reagents (Scheme 25). [37] Various substrates bearing aryl, heteroaryl, alkyl, and other functional groups were compatible in this transformation and gave the cyanated isoxazolines in good to high yields. Then, a reasonable mechanism was proposed.…”

Radical Cyclization-Initiated Difunctionalization Reactions of Alkenes and Alkynes

“…Zhang and coworkers, in 2018, reported a Ru-catalyzed radical reaction of alkenyl oximes for the synthesis of 5-cyanated isoxazolines. The reaction of alkenyl oximes 166 and TBN catalyzed with RuCl 2 ( p -cymene)] 2 and MgSO 4 in CH 3 CN at room temperature for 4 h gave 5-cyanated isoxazolines 167 in good to high yields ( Scheme 39 ) [ 64 ]. In the reaction process, TBN acts as an oxidant and a nitrogen source to avoid the use of toxic radical initiators or cyanide reagents.…”

Radical Cyclization-initiated Difunctionalization Reactions of Alkenes and Alkynes

“…Zhang and coworkers, in 2018, reported a Ru-catalyzed radical reaction of alkenyl oximes for the synthesis of 5-cyanated isoxazolines. The reaction of alkenyl oximes 166 and TBN catalyzed with RuCl2(p-cymene)]2 and MgSO4 in CH3CN at room temperature for 4 h gave 5-cyanated isoxazolines 167 in good to high yields (Scheme 39) [64]. In the reaction process, TBN acts as an oxidant and a nitrogen source to avoid the use of toxic radical initiators or cyanide reagents.…”