Selectivity

Organic chemistry

Combinatorial chemistry

Allene

Catalysis

Medicinal chemistry

Stereoselectivity

Chemistry

Quinoline

Cobalt

Regioselectivity

Angewandte Chemie International Edition

An efficient Cp*CoIII -catalyzed C8-dienylation of quinoline-N-oxides was achieved by employing allenes bearing leaving groups at the α-position as the dienylating agents. The reaction proceeds by CoIII -catalyzed C-H activation of quinoline-N-oxides and regioselective migratory insertion of the allene followed by a β-oxy elimination, leading to overall dienylation. Site-selective C-H activation was achieved with excellent selectivity under mild reaction conditions, and 30 mol % of a NaF additive was found to be crucial for the efficient dienylation. The methodology features high stereoselectivity, mild reaction conditions, and good functional-group tolerance. C8-alkenylation of quinoline-N-oxides was achieved in the case of allenes devoid of leaving groups as coupling partners. Furthermore, gram-scale preparation and preliminary mechanistic experiments were carried out to gain insights into the reaction mechanism.

Cobalt‐Catalyzed C8‐Dienylation of Quinoline‐<i>N</i>‐Oxides

Cobalt‐Catalyzed C8‐Dienylation of Quinoline‐N‐Oxides