Efficient Synthesis of N‐Alkylated 4‐Pyridones by Copper‐Catalyzed Intermolecular Asymmetric Propargylic Amination

Abstract

Copper-catalyzed intermolecular asymmetric propargylic amination with 4-hydroxypyridines has been realized for the first time. In the presence of Cu complex derived from Pybox ligand, the N-propargylated 4-pyridones were obtained under mild reaction conditions with up to 99 % yield and 95 % ee. The Pybox ligand bearing a 4-F-phenyl substituent plays a key role for the high enantioselectivity. The products can be easily transformed to the core structure of quinolizidine alkaloids.

Synthesis of γ-Pyrones and N-Methyl-4-pyridones via the Au Nanoparticle-Catalyzed Cyclization of Skipped Diynones in the Presence of Water or Aqueous Methylamine

“…As the core skeleton of 4-pyridone appears in a series of bioactive compounds, several synthetic approaches for the synthesis of this class of compounds have been developed so far. The most prominent include the treatment of γ-pyrones with amines, which is a slow process but can be promoted on certain types of pyrones (maltols) by boronic acids, via 4-alkoxy pyridinium salts under basic conditions; the Cu­(I)-catalyzed reaction of 4-hydroxypyridines with propargylic acetates, via the dehydrogenation of 2,3-dihydro-4-pyridones; the three-component cascade reaction of anilines, ethoxymethyl enemalonates, and acetylenedicarboxylates; the [4 + 2] cycloaddition between 3-aminocyclobutenones and electron-deficient alkynes; and the transition-metal-catalyzed N -allylation of parent 4-pyridone with allenes . We emphasize that the catalyzed approach for the synthesis of 4-pyridones using skipped diynones as precursors is practically underexamined.…”

Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination with Pyridones

“…On the other hand, the desired allylic amination products from 4‐pyridones are prone to isomerize to the corresponding internal alkenes under basic conditions, which diminished the enantioselectivity [8b] . Indeed, a catalytic system allowing alkylation of 4‐pyridones with high chemo‐, regio‐ and enantioselectivities remains underexplored [8a,9] . Herein, we report an efficient synthesis of chiral N ‐substituted pyridones by Ir‐catalyzed asymmetric allylic amination reaction with both 4‐ and 2‐pyridones in a highly chemo‐, regio‐, and enantioselective manner (Scheme 1c).…”

Recent Advances in the Creation of Asymmetric Carbon Centre(s) by Generation of Carbon‐Heteroatom Bond(s) Using Metal‐Pybox Complexes

“…Recently You et al . wisely used Cu‐pybox complex catalyzed asymmetric propargylic amination for the synthesis of N‐alkylated 4‐pyridones using 4‐hydroxypyridines as the coupling partner with propargylic esters (Scheme ) . Initial studies were carried out using 4‐hydroxypyridine and propargylic acetate as model substrates with well‐established CuI‐pyridine‐2,6‐bisoxazoline catalytic system; but the yield was not promising.…”