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

Kwabena Fobi; Ebenezer Ametsetor; Richard A Bunce

doi:10.3390/molecules28155856

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

Molecules. 2023 Aug 3;28(15):5856. doi: 10.3390/molecules28155856.

Authors

Kwabena Fobi¹, Ebenezer Ametsetor¹, Richard A Bunce¹

Affiliation

¹ Department of Chemistry, Oklahoma State University, Stillwater, OK 74078-3071, USA.

Abstract

A domino aldol-S_NAr-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 S_NAr 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: 1,8-naphthyridin-2(1H)-ones; [3+3] annulation; aldol-SNAr-dehydration reactions; domino reactions; heterocycle synthesis; quinolin-2(1H)-ones.

Grants and funding

BIR-9512269/National Science Foundation