Direct catalytic synthesis of β-acylamino cyclobutanones via three-component Mannich reactions
Bence S Nagy1, Fegyverneki Dániel1, Péter Szalai1,2
1Servier Research Institute of Medicinal Chemistry, Záhony u. 7, Budapest, H-1031, Hungary. andras.kotschy@servier.com.
Abstract:
Herein, a versatile, robust, and solvent-free method is reported for the synthesis of novel β-acylamino cyclobutanone derivatives exploiting a Cu(OTf)2/TIPSCl-promoted Mannich-type three-component approach. The present work expands the utilization of a ring-strained ketone as well as various amide derivatives as amine equivalents, which has remained relatively underexplored due to their low reactivity profile. Following a rapid optimization of the reaction conditions, a relevant set of β-acylamino cyclobutanone derivatives has been designed and generated. Furthermore, the synthetic utility of our process has been demonstrated via a dual Au(I)/Ag(I)-catalyzed intramolecular hydroxygenation reaction to showcase a representative post-Mannich transformation.
Related Concept Videos
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Cycloaddition Reactions: Overview
Alkenes via Reductive Coupling of Aldehydes or Ketones: McMurry Reaction
α-Hydroxy Ketones via Reductive Coupling of Esters: Acyloin Condensation Overview
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Alkylation of β-Diester Enolates: Malonic Ester Synthesis


