Domino Synthesis of 3‐Alkyliden‐2,3‐Dihydro‐4‐Quinolones

Abstract

The synthesis of 3-alkyliden-2,3-dihydro-4-quinolones has been accomplished in a domino fashion through a three-step sequence that comprised an initial aza-Baylis-Hillman reaction, followed by a 1,3rearrangement and an intramolecular amination. Starting from readily available aryl vinyl ketones and Ntosyl imines, the reaction with PPh 3 , CsOAc and CuI in CH 3 CN gave rise, in good overall yields, to final 3alkyliden-4-quinolone derivatives, valuable scaffolds in medicinal chemistry. The simultaneous addition of two bases, PPh 3 and CsOAc, was found to be crucial for the success of the process. While PPh 3 promoted the reversible aza-Baylis-Hillman reaction, CsOAc triggered the subsequent 1,3-rearrangement, which shifted the initial equilibrium and allowed to complete the synthetic sequence upon the addition of CuI.

One‐pot Synthesis of 3‐Aryliden‐2,3‐dihydro‐4‐quinolones from o‐Anilinopropargyl Alcohols via Aldol Condensation of In Situ Generated 2,3‐Dihydroquinolin‐4‐ones and Aryl Aldehydes

“…The deprotection of the Ts group in 2 a was attempted, and (E) ‐3‐benzylidene‐2,3‐dihydroquinolin‐4(1 H )‐one H was obtained in 70% yield after stirring the mixture of 2 a and TfOH (2 equiv.) in DCE for 24 h at room temperature [6a] . Refluxing 2 a and hydrazine hydrate with AcOH as the solvent led to N ‐acetylated pyrazoloquinoline derivative J in 80% yield, and N ‐free pyrazoloquinoline derivative I in 60% yield with DMF as the solvent [1c] …”

Recent Developments in the Synthetic Strategies of 4‐Quinolones and Its Derivatives

“…materials and good yields were the key highlights of the developed protocol. [71] A simple, facile, highly efficient one-pot synthesis of 4quinolones (107) from 1-(2-aminophenyl)ethanone (105) was developed by Arava and Bandatmakuru. It was observed that excellent yields of title compounds (106) were obtained when the cyclization between 1-(2-aminophenyl)ethanone (105) and dimethylformamide dimethyl acetal (DMFDMA, 106) was carried out in the presence of para-toluenesulfonic acid (PTSA, 0.1 mol) as a catalyst in ortho-xylene as a solvent at 130°C [scheme 32].…”

“…Proposed mechanism of synthesis of 4-quinolones using visible light.provided the best yields of 2,3-dihydro-1,2(substituted)-4quinolones(71) [scheme 23, entry 1]. Both Cbz and Boc protected quinolones performed well under the optimized reaction conditions while the use of methylcarbamate ester was not effective and resulted in poor yields.…”

Synthesis and Functionalization of 4‐Quinolones – A Progressing Story

“…In recent year, Pozo et al reported a domino approach for the synthesis of 3‐alkyliden‐2,3‐dihydro‐4‐quinolones 132 starting from ortho ‐bromo aryl vinyl ketones and N ‐tosyl imines through a three‐step sequence that mainly comprised of an initial aza‐Baylis–Hillman reaction, followed by a 1,3‐rearrangement and an intramolecular amination reaction (Scheme ) . Various tosylamine (aromatic and heteroaromatic), arylbromo ketones were effectively participated in the reaction and furnished the substituted dihydro‐4‐quinolones in good yields.…”