Regioselective Pd-catalyzed direct C1-and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

Hai-Yun Huang (1) , Haoran Li (1) , Thierry Roisnel (1) , Jean-François Soulé (1) , Henri Doucet (1)

1 ISCR - Institut des Sciences Chimiques de Rennes

The Pd-catalyzed C-H bond functionalization of lilolidine was investigated. The use of a palladium-diphosphine catalyst associated to acetate bases in DMA was found to promote the regioselective arylation at alpha-position of the nitrogen atom of lilolidine with a wide variety of aryl bromides. From these alpha-arylated lilolidines, a second arylation at the beta-position gives the access to alpha,beta-diarylated lilolidines containing two different aryl groups. The one pot access to alpha,beta-diarylated lilolidines with two identical aryl groups is also possible by using a larger amount of aryl bromide. The synthesis of 5,6-dihydrodibenzo[a,c]pyrido[3,2,1-jk]carbazoles from lilolidine via three successive direct arylations is also described. Therefore, this methodology provides a straightforward access to several lilolidine derivatives from commercially available compounds via one, two or three C-H bond functionalization steps allowing to tune their biological properties.

Keywords: palladium; catalysis C-C bond formation; C-H bond activation; lilolidine

Domains: Chemical Sciences; Organic chemistry; Chemical Sciences; Catalysis; Chemical Sciences; Medicinal Chemistry

Hai-Yun Huang, Haoran Li, Thierry Roisnel, Jean-François Soulé, Henri Doucet. Regioselective Pd-catalyzed direct C1-and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives. Beilstein Journal of Organic Chemistry, 2019, 15, pp.2069-2075. ⟨10.3762/bjoc.15.204⟩. ⟨hal-02303387⟩