A Catalytic Strategy for α,ω‐Functionalization: NHC‐Mediated Fragmentation/Umpolung Cascades to Access Hydroxytrifluoromethyl Ynones and Allenones

Herein we report an unprecedented, convenient NHC‐catalyzed one‐pot cascade reaction to afford α,ω‐difunctionalized hydroxytrifluoromethyl alkynones and allenones in a single step. The critical fragile aliphatic aldehydes are introduced by a base‐mediated in situ Grob‐type fragmentation of their corresponding latent cyclic vinylogous hemiacetal triflate (VHAT) and γ‐hydroxy vinyl triflate (GHVT) precursors, avoiding typical problems and losses upon isolation. The ′demasked′ aldehydes are subsequently trapped by NHC‐catalyzed umpolung and further metal‐free C−C‐cross‐coupling to access a broad scope of terminally modified alkynyl or allenyl aliphatic, aromatic and heteroaromatic trifluoromethyl ketones as multifunctionalized, high‐value building blocks for advanced synthetic applications. Additional synthetic utility of this approach is demonstrated with the possibility for asymmetric variants using chiral NHC‐catalysts. Cutting the cord: In situ generation of substrates from their stable ‘masked’ precursors is an elegant way to introduce fragile species into cascade reactions. Herein, a versatile one‐pot procedure, combining variants of Grob‐fragmentation with modern NHC‐catalysis affording α,ω‐multifunctionalized hydroxytrifluoromethyl ketones, is reported.