RESUMO
Presented herein is the synthesis of diversely functionalized pyrrolizines from the reaction of N-alkoxycarbamoyl pyrroles with CF3-ynones. The formation of the product is based on a C-H bond activation-initiated cascade process including N-alkoxycarbamoyl group-directed alkenylation of the pyrrole scaffold followed by simultaneous intramolecular nucleophilic addition along with cleavage and transfer of the directing group. By taking advantage of the rich chemistry of the transferred alkoxycarbamoyl moiety, the products could be transformed into a series of structurally and biologically interesting pyrrolizine derivatives. To our knowledge, this is the first example in which the N-alkoxycarbamoyl unit acted as a transferable and transformable directing group for the divergent synthesis of pyrrolizines.
RESUMO
Presented herein is a novel synthesis of CF3-substituted pyrrolo[1,2-a]indole derivatives based on the cascade reactions of N-alkoxycarbamoyl indoles with CF3-ynones. Mechanistically, the formation of a product involves a tandem process initiated by Rh(III)-catalyzed and N-alkoxycarbamoyl group-directed regioselective C2-H alkenylation of the indole scaffold followed by in situ removal of the directing group and intramolecular N-nucleophilic addition/annulation under one set of reaction conditions. To our knowledge, this is the first example in which a N-alkoxycarbamoyl unit initially acts as a directing group for C2-H functionalization of the indole scaffold and is then removed to provide the required reactive NH-moiety for subsequent intramolecular condensation. Moreover, the products thus obtained could be conveniently transformed into structurally and biologically attractive cycloheptenone fused indole derivatives through an acid-promoted cascade transformation. In addition, studies on the activity of selected products against human cancer cell lines demonstrated their potential as lead compounds for the development of novel anticancer drugs.
