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

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.