Influence of Achiral Phosphine Ligands on a Synergistic Organo‐ and Palladium‐Catalyzed Asymmetric Allylic Alkylation
David McLeod, Nicolaj Inunnguaq Jessen, Thanh V. Q. Nguyen, Marcus Espe, Jeremy D. Erickson, Karl Anker Jørgensen, Limin Yang, K. N. Houk
Abstract
An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.