1618673-05-4Relevant academic research and scientific papers
A Direct, Versatile, and Chemoselective Synthesis of Vinylogous Bis- and Monourethanes/amides and β-Keto Esters by Aza-Knoevenagel-Type Reactions of Tertiary Amides with Enolates
Huang, Pei-Qiang,Ou, Wei
, p. 582 - 592 (2017/02/05)
Full details of our investigations into aza-Knoevenagel-type reactions with common tertiary amides as the electrophilic partner are reported. The method is based on the addition of stabilized carbanionic nucleophiles to the amides, which are activated in situ with triflic anhydride (Tf2O). The reaction proceeds under mild conditions and tolerates several sensitive functional groups including enamide and tert-butyldimethylsilyloxy (TBSO) groups. Significantly, with amides bearing more reactive ester, cyano, and aldehyde groups, the reaction occurs chemoselectively at the least reactive amide group. Such “umpolung” of the chemoselectivity in C=C bond formation is challenging, rare, and of synthetic value. Vinylogous bis-urethanes (aza-Knoevenagel-type condensation products), vinylogous urethanes, and vinylogous amides can be synthesized by employing enolates/carbanions generated from methyl ketones, malonic acid monoester, 2-phenylacetate, or (benzylsulfonyl)benzene. Moreover, when higher homologues of acetate were used, β-keto esters were obtained directly from amides. The method has been applied to the one-step syntheses of several known key intermediates in the total syntheses of alkaloids and 4-quinolone antibiotics. An efficient and mild intramolecular Friedel–Crafts-type cyclization of an anilinyl ester has also been achieved with Tf2O as an effective promoter. This amide-based method is a direct and umpoled alternative to the versatile but stepwise one based on thionation and the Eschenmoser sulfide contraction.
Tertiary amide-based Knoevenagel-type reactions: A direct, general, and chemoselective approach to enaminones
Huang, Pei-Qiang,Ou, Wei,Xiao, Kai-Jiong,Wang, Ai-E.
supporting information, p. 8761 - 8763 (2014/07/22)
We report one-pot and chemoselective Knoevenagel-type reactions using highly stable amides and lactams as the electrophilic substrates. The method is based on the in situ activation of amide carbonyl with triflic anhydride and a subsequent reaction with carbanions generated in situ from carbonyl compounds. The amide-based method is an alternative to the versatile thioamide-based Eschenmoser sulfide contraction.
