Enantioselective propargylic [1,3]-rearrangements: copper-catalyzed O-to-N migrations toward C–N bond formation

Abstract

We have identified an enantioselective copper-catalyzed O-to-N formal [1,3]-rearrangement to form N-propargylic-2-pyridones.

Scope and advances in the catalytic propargylic substitution reaction

“…77 The reaction proceeded under mild reaction conditions with high efficiency and excellent regioselectivity. Low yields were only observed when other conventional diamine ligands (111)(112)(113)(114)(115)(116)(117) were used along with the nickel catalyst, Fig. 3.…”

“…Cordier and co-workers in the year 2017 have developed the rst enantioselective Cu-catalyzed rearrangement of electron-decient 2-propargyloxy-pyridines 192 in high enantioselectivity within a brief time, Scheme 83. 113 The nature of copper catalyst had a strong inuence on both conversion and enantioselectivity. Ligands like diphenyl-and di-4-methylphenyl-phosphines (188,193, 193a-f) Fig.…”

Visual kinetic analysis

“…VTNA has already been used successfully by academic and industrial research groups in metal-catalysed [25][26][27][28][29][30][31][32][33][34][35][36][37][38] and organocatalytic reactions. [39][40][41][42][43]…”

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

“…However, the reported nucleophilic nitrogen sources were mainly limited to primary and secondary anilines . Despite the great importance of amides, they have been rarely studied in Cu‐catalyzed propargylic substitution reactions . Herein, we describe the first enantioselective synthesis of N ‐substituted 4‐pyridones through the propargylic amination with 4‐pyridones.…”

“…[7] Several elegant examples have been disclosed, furtherb roadening the scope and applicability of methods for the preparation of enantioenriched propargylic amines.H owever,t he reported nucleophilic nitrogen sources were mainly limited to primary and secondary anilines. [9] Herein, we describe the first enantioselective synthesis of Nsubstituted 4-pyridones through the propargylic amination with 4-pyridones. [9] Herein, we describe the first enantioselective synthesis of Nsubstituted 4-pyridones through the propargylic amination with 4-pyridones.…”