Chan-Evans-Lam N 1-(het)arylation and N 1-alkеnylation of 4-fluoroalkylpyrimidin-2(1 H)-ones

Viktor M Tkachuk; Oleh O Lukianov; Mykhailo V Vovk; Isabelle Gillaizeau; Volodymyr A Sukach

doi:10.3762/bjoc.16.191

Chan-Evans-Lam N 1-(het)arylation and N 1-alkеnylation of 4-fluoroalkylpyrimidin-2(1 H)-ones

Beilstein J Org Chem. 2020 Sep 17:16:2304-2313. doi: 10.3762/bjoc.16.191. eCollection 2020.

Authors

Viktor M Tkachuk¹, Oleh O Lukianov¹, Mykhailo V Vovk¹, Isabelle Gillaizeau², Volodymyr A Sukach^{1

3}

Affiliations

¹ Institute of Organic Chemistry, National Academy of Sciences of Ukraine.
² Institute of Organic and Analytical Chemistry, ICOA UMR 7311 CNRS, Université d'Orléans, rue de Chartres, 45100 Orléans, France.
³ Enamine LTD, 78 Chervonotkats'ka str., Kyiv 02094, Ukraine.

Abstract

The Chan-Evans-Lam reaction of 1-unsubstituted 4-fluoroalkylpyrimidin-2(1Н)-ones with arylboronic acids is reported as a facile synthetic route to hitherto unavailable N1-(het)aryl and N1-alkenyl derivatives of the corresponding pyrimidines. An efficient C-N bond-forming process is also observed by using boronic acid pinacol esters as coupling partners in the presence of Cu(II) acetate and boric acid. The 4-fluoroalkyl group on the pyrimidine ring significantly assists in the formation of the target N1-substituted products, in contrast to the 4-methyl and 4-unsubstituted substrates which do not undergo N1-arylation under similar reaction conditions.

Keywords: Chan–Evans–Lam reaction; C–N cross-coupling; boronic acids; fluoroalkyl group; pyrimidin-2(1Н)-ones.