Convenient Synthesis of Acyclic Amidines via Copper‐Catalyzed C(sp³)‐H Amidination

Abstract

A convenient synthetic approach for the synthesis of α‐oxo‐acetamidines via copper‐catalyzed C(sp3)‐H amidination has been developed. This approach allows the direct amidination of three C(sp3)‐H bonds without cyclization.Methyl ketones and primary and secondary amines are tolerant and afford the corresponding products in moderate to good yields. Furthermore, this protocol is also applicable to the synthesis of unsymmetrical α‐oxo‐acetamidines via one‐pot, multicomponent reactions (MCRs).

A single‐step synthesis of 1,3,4,6‐tetraaryl‐5‐aryliminopiperazin‐2‐one

“…In the case of Entry 1, for instance, a modified Möhalu‐Bischler indole synthesis method was used to form 2‐phenylindole from phenylglyoxal and aniline [1]. Further, the oxidative amination of glyoxals can be efficiently used to prepare α‐ketoamidines (Entry 2) [2] or α‐ketoamides (Entry 3) [3]. Moreover, Povarov conditions have been used (Entry 4) in a three‐component reaction involving an alkene (eg, dihydrofuran), aniline, and phenylglyoxal in the presence of a Lewis acid catalyst to obtain 4‐benzoyl‐2,3,3a,4,5,9b‐hexahydrofuro[3,2‐ c ]quinoline [4].…”

“…We were interested in designing modular peptidomimetics such as 1,2,3,4-tetrahydroquinolines with appended 2-acyl groups as new antiviral agents (Scheme 1) [5]. Therefore, we reacted phenylglyoxal (1), aniline (2), and olefins (3) under Povarov conditions [6] with the aim of obtaining 4-oxysubstituted compounds 4 (Scheme 1).…”

A Single-Step Synthesis of 1,3,4,6-Tetraaryl-5-Aryliminopiperazin-2-One

“…In the case of Entry 1, for instance, a modified Möhalu-Bischler indole synthesis method was used to form 2phenylindole from phenylglyoxal and aniline [1] . Further, the oxidative amination of glyoxals can be efficiently used to prepare α-ketoamidines (Entry 2) [2] or α-ketoamides (Entry 3) [3] . Moreover, Povarov conditions have been used (Entry 4) in a threecomponent reaction involving an alkene (e.g., dihydrofuran), aniline, and phenylglyoxal in the presence of a Lewis acid catalyst to obtain 4-benzoyl-2,3,3a,4,5,9b-hexahydrofuro [3,2-c]quinoline [4] .…”

“…We were interested in designing modular peptidomimetics such as 1,2,3,4-tetrahydroquinolines with appended 2-acyl groups as new antiviral agents (Scheme 1) [5] . Therefore, we reacted phenylglyoxal (1), aniline (2), and olefins (3) under Povarov conditions [6] with the aim of obtaining 4oxysubstituted compounds 4 (Scheme 1).…”