Herein, an Ir-catalyzed asymmetric allylic substitution reaction of methyl azaarenes is described. Azaarenes such as (benzo)thiazole, oxazole, benzoimidazole, pyridine, and (iso)quinoline are all tolerated. The corresponding chiral azaarene derivatives are obtained in good yields with high enantioselectivity (up to 96 % yield and 99 % ee). The utilization of the Knochel reagent TMPZnBr⋅LiBr warrants the in situ formation of benzylic nucleophiles without additional activating reagents. 1 H NMR studies suggested a two-fold function of the Knochel reagent in this reaction. The synthetic utility of this method has been showcased by a concise enantioselective synthesis of an allosteric protein kinase modulator.

Quaternary stereocenters are of great importance to the three-dimensionality and enhanced properties of new molecules, but the synthetic challenges in creating quaternary stereocenters greatly hinder their wide use in drug discovery, organic material design, and natural product synthesis. The asymmetric allylic alkylation (AAA) of allylic substrates has proven to be a powerful methodology for enantioselective formation of structure skeletons bearing single or more quaternary carbon centers in modern asymmetric organocatalysis. AAA has certain advantages in constructing the tetrasubstituted stereocenters, including but not limited to mild reactive conditions, effective reaction rates, new functional group introduction, and carbon chains length extension. This review outlines the key considerations in the application of AAA reactions and summarizes the recent progress of AAA reactions in the enantioselective synthesis of products containing quaternary stereocenters. Meanwhile, a detailed discussion of the AAA reactions such as ligands, scope of substrates, transformations and the general reaction mechanisms is also provided. We hope this review could stimulate further advances in much broader areas, including organic synthesis, asymmetric catalysis, C-H activation, and symmetrical pharmaceutical chemistry.

An efficient dual catalytic system composed of a chiral primary amine and a palladium complex was developed to promote the direct asymmetric allylic alkylation (AAA) of β-ketocarbonyl compounds. In particular, the synergistic dual catalytic system enabled the AAA reaction of challenging acyclic aliphatic ketones, such as β-ketocarbonyl compounds and 1,3-diketones.