Enantioselective Annulation Reactions: From Fischer Indolization to de novo Arene Construction

Abstract

In summary, we have developed the first decarboxylative [4+2]-annulation of ethynyl benzoxazinanones with azlactones for the enantioselective synthesis of cyclic α-quaternary α-acylaminoamides.25 This direct and modular approach combines dipolar copper-allenylidene intermediates and enolates generated from azlactones under bifunctional tertiary aminourea catalysis in a cooperative fashion. The resulting 3,4-dihydroquinolin-2-ones 3.43, bearing vicinal tertiary and quaternary stereogenic centers, are formed as a single diastereomer with good to excellent enantioselectivity. The products are densely functionalized and the synthetic versatility of the terminal alkyne group is demonstrated through a number of synthetic elaborations. This reaction represents the first direct catalytic enantioselective route to cyclic α-quaternary α-acylaminoamides