Direct [3+2] Cycloaddition-Dearomative-Alkylation Cascade: Simple Terminal Alkynes to Indoline-fused-3,4-Pyrroles

Natural products offer powerful bioactive compounds that serve as leads for new-age therapeutics. Alkaloid natural products containing C3-alkylated indolines embed an all-carbon quarternary ring system that is we documented as a privileged scaffold in natural product chemistry and drug design. Inspired by the Nocardioazines A and B that are prenylated, bioactive pyrroloindoline natural products, isolated from Nocardiopsis, we envisioned that Indoline-fused- 3,4-pyrroles offer a new scaffold to explore their biological importance. A biomimetic pathway that provides access to 6-5-6-5 and 6-5-7-5 C3-alkylated indoline-3,4-pyrrole fusion products that are new to heterocyclic chemistry is described. The reactivity profile presented in the form of a cascade process, executed smoothly as a single-pot reaction is unprecedented for three reasons, with isolated yields being high to excellent. The entire process works without any protecting groups while functionalizing two aromatic rings and the process offers indolines tethered with pyrrole at the C2 position with high regioselectivity. In summary, simple alkynes are transformed dramatically into complex natural-product-like cores smoothly, with broad substrate scope