Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones

• Published in: Tetrahedron Vol. 76; no. 43; p. 131523
• Main Authors: Belyaeva, Kseniya V., Nikitina, Lina P., Afonin, Andrei V., Trofimov, Boris A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 23.10.2020; Elsevier
• Subjects: Alkynes; Chemistry; Chemistry, Organic; Enones; Functionalization; Nucleophilic addition; Physical Sciences; Quinolines; Quinolones; Regioselectivity; Science & Technology; Quinolines; Functionalization; Regioselectivity; Enones; Alkynes; Nucleophilic addition; Quinolones; DESIGN; ONE-POT; DRUGS
• ISSN: 0040-4020; 1464-5416; 0040-4020
• DOI: 10.1016/j.tet.2020.131523

The expected one-pot multiple functionalization of hydroxyquinolines and quinolones with acylacetylenes (20 mol% KOH, 5 equiv. H2O, MeCN, 55–60 °C), which, according to the previous finding, might involve the addition of OH and NH-functions to the triple bond and insertion of acylacetylenes into the quinoline scaffold, retains mainly on the formation of chalcone-quinoline ensembles in up 99% yield. The higher functionalized quinolines can be obtained in a synthetically acceptable yield, when the above ensembles are treated with the second molecule of acylacetylenes. Thus, the further insertion of second molecule of the acetylenes into the quinoline scaffold occurs as a much slower process indicating a strong adverse substituent effect of the remote chalcone moiety. [Display omitted] •C-, O-, or N-functionalizations of quinoline core.•Broad scope, short reaction time.•Excellent product yields.