Domino Aldol-S_NAr-Dehydration Sequence for [3+3] Annulations to Prepare Quinolin-2(1<i>H</i>)-ones and 1,8-Naphthyridin-2(1<i>H</i>)-ones

Abstract

A domino aldol-SNAr-dehydration [3+3] annulation strategy has been utilized to fuse six-membered cyclic amides onto aromatic substrates. 2-Arylacetamides have been reacted with 2-fluorobenzaldehyde derivatives activated toward SNAr reaction by an electron-withdrawing substituent (NO2, CN, CF3, CO2Me) at C5 to prepare 3,6-disubstituted quinolin-2(1H)-ones. Additionally, 3-substituted 1,8-naphthyridin-2(1H)-ones have been similarly derived from 2-fluoronicotinaldehyde. Fifteen examples are reported, and two possible mechanistic scenarios are presented and discussed.

Keywords

• quinolin-2(1<i>H</i>)-ones
• 1,8-naphthyridin-2(1<i>H</i>)-ones
• heterocycle synthesis
• aldol-S_NAr-dehydration reactions
• domino reactions
• [3+3] annulation