Steric and Electronic Requirements in the Synthesis of 2,3‐Dihydro‐4(1H)‐quinolinones by the Tandem Michael‐SNAr Reaction

Abstract

The steric and electronic requirements have been investigated for the synthesis of 2,3‐dihydro‐4(1H)‐quinolinones by the tandem Michael‐SNAr reaction. Substrates bearing a single methyl group at the β‐enone carbon gave excellent yields of the title compounds from both the E and Z isomers with X═H or NO2. Substrates with β,β‐dimethyl substitution at the Michael terminus gave low yields of heterocyclic products in molecules having monoactivated SNAr aromatic acceptor rings (X═H) and very good yields for diactivated systems (X═NO2). For these hindered substrates, success in the final cyclization hinges on the ability of the aromatic acceptor to capture the pendant nitrogen nucleophile of the initial Michael adduct before this intermediate can revert to starting materials.