Nucleophilic activation of a nitrile group: Synthesis of trifluoromethyl substituted 4H-1,3,5-dioxazines

The negatively charged carbon atom of phosphorus ylides is capable of increasing the nucleophilicity of the triple CN bond. The nitrile group activated in this way can add two equivalents of hexafluoroacetone with the formation of trifluoromethyl substituted 4H-1,2,3-dioxazines. Due to delocalization of the ylidic negative charge one of the C–C bonds acquires a double bond character, the consequence of which is the existence of E/Z-isomerism in these compounds.

Graphical abstractThe negatively charged carbon atom of phosphorus ylides activates the nucleophilicity of the adjacent nitrile group. Such nitriles can add two equivalents of hexafluoroacetone to the CN triple bond to give 4H-1,3,5-dioxazines. Depending on the substituents at phosphorus atom this reaction can go stereoselectively with the formation of only one isomer.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► A carbanion in α-position to a nitrile group increases its nucleophilicity. ► A CN group activated by phosphorus ylides adds hexafluoroacetone to give 4H-1,3,5-dioxazines. ► 4H-1,3,5-Dioxazines eliminate one molecule of hexafluoroacetone to give acylimines.