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Domino Synthesis of 3‐Alkyliden‐2,3‐Dihydro‐4‐Quinolones
Author(s) -
Raga Esther,
Escolano Marcos,
Torres Javier,
RabasaAlcañiz Fernando,
SánchezRoselló María,
del Pozo Carlos
Publication year - 2019
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201801490
Subject(s) - chemistry , domino , intramolecular force , amination , sequence (biology) , aryl , quinolone , combinatorial chemistry , cascade reaction , medicinal chemistry , stereochemistry , organic chemistry , catalysis , biochemistry , alkyl , antibiotics
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 1,3‐rearrangement and an intramolecular amination. Starting from readily available aryl vinyl ketones and N ‐tosyl imines, the reaction with PPh 3 , CsOAc and CuI in CH 3 CN gave rise, in good overall yields, to final 3‐alkyliden‐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.