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 alpha,omega-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 gamma-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.