Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones

Kseniya V Belyaeva; Lina P Nikitina; Andrei V Afonin; Boris A Trofimov

doi:10.1016/j.tet.2020.131523

Acylacetylenes in multiple functionalization of hydroxyquinolines and quinolones

Tetrahedron. 2020 Oct 23;76(43):131523. doi: 10.1016/j.tet.2020.131523. Epub 2020 Aug 20.

Authors

Kseniya V Belyaeva¹, Lina P Nikitina¹, Andrei V Afonin¹, Boris A Trofimov¹

Affiliation

¹ A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of Russian Academy of Sciences, 1 Favorsky Str., Irkutsk, 664033, Russian Federation.

Abstract

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.

Keywords: Alkynes; Enones; Functionalization; Nucleophilic addition; Quinolines; Quinolones; Regioselectivity.