Regio- and Stereoselective Synthesis of Diverse 3,4-Dihydro-2-quinolones through Catalytic Hydrative Cyclization of Imine- and Carbonyl-Ynamides with Water

Abstract

Transition-metal-catalyzed alkyne hydration reaction has attracted considerable interest in the past decades because this approach would lead to the facile and efficient formation of synthetically useful carbonyls. However, transition-metal-catalyzed alkyne hydration-initiated tandem reactions have seldom been explored because their metal enolate intermediates generally undergo facile protodemetallation rather than further trapped by other types of electrophiles. Described herein is an efficient coppercatalyzed tandem alkyne hydration/intramolecular Mannich reaction of imine-ynamides with water. This method allows efficient and diastereodivergent synthesis of valuable 3,4-dihydro-2-quinolones with high regio-, diastereo-, and enantioselectivity. Moreover, this hydrative cyclization can also be applicable to the hydrative aldol reaction of carbonyl-ynamides with water to form 3,4-dihydro-2-quinolones regio-and diastereoselectively by employing zinc as the catalyst.

Photoinduced ynamide structural reshuffling and functionalization

“…Based on the results of the above control experiment, previous 1 – 11 , 37 – 40 , 47 , 54 – 64 , 69 , 70 reports and our own research experience 41 , a plausible mechanism is depicted in Fig. 9 for compounds 3 ′, 51 and 76 (Supplementary Fig.…”

Recent advances in the synthesis of pharmaceutically active 4-quinolone and its analogues: a review

“…Transitionmetal-based catalysts are essential for achieving a wide range of benecial chemical transformations that would otherwise be difficult or impossible to achieve. 31 3.2.1 Palladium-catalyzed synthesis. In 2010, Zhao and coworkers reported the palladium-catalyzed synthesis of N-aryl-4-quinolones 67 from o-haloaryl acetylenic ketones 65 and primary amines 66 in PPh 3 as a ligand, K 2 CO 3 as a base and dioxane as a solvent.…”

“…Transition-metal-based catalysts are essential for achieving a wide range of beneficial chemical transformations that would otherwise be difficult or impossible to achieve. 31…”

TMSOTf-Catalyzed [4 + 2] Annulation of Ynamides and β-(2-Aminophenyl)-α,β-ynones for the Synthesis 2-Aminoquinolines

“…Ynamides, as a subclass of nitrogen-atom-substituted alkynes, have attracted considerable attention due to their ability to provide structurally diverse nitrogen-containing heterocycles through transformations such as regioselective difunctionalization and annulation reactions . In recent years, transition-metal-catalyzed annulations of ynamides have offered broad prospects for the efficient generation of 2-aminoquinolines. − In 2016, Hashmi et al described a gold-catalyzed annulation of ynamides with anthranils for the synthesis of 2-aminoquinolines (Scheme a) .…”