Base-controlled regioselective functionalization of aromatic indolizines

Over the last few years, indolizines have received great attention due to its successful application in many fields, such as agrochemicals, pharmaceuticals and in medicinal chemistry. This success is because indolizine scaffolds have been found in many bioactive natural products, drug molecules and organic fluorescent materials. Consequently, many synthetic strategies have been developed for the construction of new functionalized indolizines. Among the most important methodologies are Tschitschibabin reaction, 1,3-dipolar cycloadditions, cycloisomerization and intramolecular cyclization. In this work, we have investigated the preparation of substituted indolizines through a base-controlled regioselective functionalization of molecules 1, 4 and 7 using alkyl lithium or lithium amides and TMPMgCl∙LiCl. It was possible to observe C-2 or C-5 selectivity depending on the basis for substrate 1, C-3 or C-5 selectivity depending on the electrophile for substrate 4 and mixture of C-2 and C-5 products for indolizine 7 for both bases (Scheme 1).