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A Catalytic Strategy for α,ω‐Functionalization: NHC‐Mediated Fragmentation/Umpolung Cascades to Access Hydroxytrifluoromethyl Ynones and Allenones
Author(s) -
Selg Christoph,
Kraft Fabian B.,
Welcke Linda,
Zeitler Kirsten
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201801454
Subject(s) - umpolung , trifluoromethanesulfonate , chemistry , combinatorial chemistry , catalysis , organocatalysis , carbene , aldol reaction , organic chemistry , enantioselective synthesis , nucleophile
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.