Indolizine Functionalization Promoted by Abundant-earth Metals

N-heterocycles are among the most common building blocks for biologically active substances.¹ Among them are indolizines, a class of fused bicyclic compounds with interesting photophysical and biological activities.^2,3 Given the potential of this heterocyclic class, methodologies that allow functionalization while avoiding the use of expensive and rare metals such as Rh, Ir and Pd are highly valuable Aiming to enable the functionalization of indolizines promoted by abundant-earth metal catalysis, organomagnesium and organozinc derivatives were prepared from indolizines containing either a directed metalation group (DMG) or a heteroarylmethyl chloride substituent. These species were reacted with alkyl, benzyl and allyl halides in the presence of catalytic amounts of either cobalt or copper salts at room temperature to afford substituted derivatives with yields of up to 90%. Thus, this study demonstrates the applicability of earth-abundant metal catalysis for the efficient synthesis of functionalized indolizines with relevant chemical and biological properties.