Copper(I)-Catalyzed Annulation Route to Indolizines

Significance

Reported is the synthesis of indolizines 3 via the copper(I)-catalyzed [3+2] cyclization of pyridines 1 with alkenyldiazoacetates 2. This method is tolerant of a wide range of sensitive functional groups due to the mild nature of the ­reaction conditions, although the yields are often moderate. Electron-rich pyridines (R^¹ = OMe, NMe₂) are unsuitable substrates, and 2-substituted pyridines also led to sluggish reactivity. Pyr­idines 1 bearing 3-substituents gave a mixture of products 3, with EWGs favoring 6-substitution and alkyl groups/halogens favoring 4-substituted products. Three examples of benzo-fused pyridine substrates 4-6 were also presented. A tentative mechanism is proposed supported by theoretical calculations.