Catalyst-controlled 5-exo and 6-endo cyclization: regiodivergent access to indolinones and dihydroquinolinones

Abstract

Five- and six-membered benzo-fused lactams are important and prevalent scaffolds in many natural products and biologically active compounds. In spite of considerable advances in their synthesis, the intramolecular alkene functionalization preferably goes through 5-exo-trig cyclization to afford five-membered ring products, while the kinetically disfavored 6-endo-trig cyclization remains largely elusive. Herein, we report a novel catalyst-controlled 5-exo/6-endo regiodivergent intramolecular aryl-aminoalkylation of alkenes. The present method affords a variety of five- and six-membered N-heterocycles simultaneously from the same simple starting materials, and both products are very useful building blocks in organic synthesis. The computational studies reveal that the bonding affinity of the alkyl radical to the metal center is the primary factor behind the divergent regioselectivity. The stronger bonding affinity to the Ni center, than that to the Pd center, causes the Ni-catalyzed reaction to commence with C–Br bond cleavage to provide an aryl radical via an outer-sphere single electron transfer (OSET) pathway, while the Pd-catalyzed reaction begins with the Giese addition of an α-amino radical to the terminal position of alkenes.