Copper‐Catalyzed Cascade Cyclization for the Synthesis of Trifluoromethyl‐Substituted Spiro‐2H‐azirines from 1,6‐Enynes

Abstract

Am ethod for the synthesiso ft rifluoromethyl CF 3 -substituted spirocyclic compounds containing with au niqueq uaternary carbon center from readily available starting materials has been developed. Ther eactionp rovides af acile access to 2H-azirines via cascade cyclization. These compounds constituteanew class of functionalized synthetic intermediates,w hich can be usedf or the synthesis of various nitrogen-containing heterocycles and biologically active CF 3 -containing compounds.

Copper/Iron‐Cocatalyzed Cascade Perfluoroalkylation/Cyclization of 1,6‐Enynes with Iodoperfluoroalkanes

“…Meanwhile, a regioselective hydrodifluoromethylation of unactivated alkenes using TMSCF 2 CO 2 Et as fluorine source was proposed by Hao and coworkers in 2014 (Scheme –) . At the same time, Liang group realized copper‐catalyzed three‐component cascade cyclizations of 1,6‐enynes using Togni's reagent as the fluorine source, successively . In addition, a palladium‐catalyzed radical cascade iododifluoromethylation/cyclization of 1,6‐enynes with ethyl difluoroiodoacetate was also developed by the same group in 2015 (Scheme –) .…”

Synthesis of various functionalized 2H‐azirines: An updated library

“…The use of enynes with a heteroatom in a linker binding the double and the triple bond permits the preparation of 5‐oxa‐1‐aza‐ and 1,5‐diazaspiro[2.4]hept‐1‐ene derivatives. A free radical mechanism involving the initial generation of a CF 3 radical was projected for this cascade reaction (Scheme 86) [110].…”

Recent Advances in Radical‐Enabled Bicyclization and Annulation/1,n‐Bifunctionalization Reactions

“…It is thought that the mechanistic pathway for the formation of spiro-2H-azirines is similar to that in the radi-cal bicyclization of 1,6-enynes, as reported by Liang'sg roup. [11] The reactioni st hought to be initiated by the generation of a CF 3 radical, which is formed from the copper(I)-catalyzed decomposition of To gni'sr eagent through aS ET process. Next, addition of the CF 3 radical to the substrate (5)l eads to the formation of radicali ntermediate 7.T wo pathways are possible for the subsequent reactiono fi ntermediate 7.I np ath a, the radicali ntermediate undergoes a 6-exo-dig cyclizationr eaction and subsequent azidation to afford intermediate 10,w hich is transformed into the target product (6)through adenitrogenative cyclization step.…”

“…The reaction proceeded through a CF 3 ‐radical‐triggered bicyclization step, which involved consecutive C−C/C−C/C=N/C−N bond‐forming processes (Scheme a). It is thought that the mechanistic pathway for the formation of spiro‐2 H ‐azirines is similar to that in the radical bicyclization of 1,6‐enynes, as reported by Liang′s group . The reaction is thought to be initiated by the generation of a CF 3 radical, which is formed from the copper(I)‐catalyzed decomposition of Togni′s reagent through a SET process.…”