Diastereotopic Group Selection in Hydroxy‐Directed Intramolecular CH Alkenylation of Indole under Oxidative Palladium(II) Catalysis

Abstract

Abstract Group‐selective palladium(II)‐catalyzed ring closures involving CH bond alkenylation are reported. The cyclization precursors contain a prochiral bis(homoallylic) alcohol unit tethered to either an arene or an indole. The homobenzylic hydroxy group in these substrates is positioned to act as a directing group in the ortho ‐selective CH bond activation prior to the cyclization event. Arene‐derived precursors reacted poorly, even when applying a protocol that had proven effective in intermolecular hydroxy‐directed CH bond alkenylations. No asymmetric induction was obtained with chiral ligands, mono‐ N ‐protected amino acids (MPAAs) in particular. Conversely, the cyclization of indole‐derived precursors was substantially more efficient, and installation of a substituent in the benzylic position rendered these intramolecular CH bond alkenylations diastereoselective. The diastereotopic group selection is high with diastereomeric ratios ranging from dr =91:9 to 94:6. magnified image