Regio- and Stereoselective Synthesis of Diverse 3,4-Dihydro-2-quinolones through Catalytic Hydrative Cyclization of Imine- and Carbonyl-Ynamides with Water
Bo‐Han Zhu, Yingqi Zhang, Hao-Jin Xu, Long Li, Guocheng Deng, Peng‐Cheng Qian, Chao Deng, Long‐Wu Ye
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 copper-catalyzed 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.