Chiral α-Amino Acid/Palladium-Catalyzed Asymmetric Allylation of α-Branched ß-Ketoesters with Allylic Amines: Highly Enantioselective Construction of All-Carbon Quaternary Stereocenters.

A new protocol has been developed for the use of allylic amines as allylating agents in the chiral α-amino acid/palladium-catalyzed asymmetric allylation of α-branched ß-ketoesters, providing highly enantioselective access to all-carbon quaternary stereocenters. Notably, the formation of a primary amine, a secondary amine, or ammonia as a byproduct has little influence on the enantioselectivity for the catalytic asymmetric synthesis of structurally diverse α,α-disubstituted ß-ketoesters.

Highly Regioselective Aromatic C-H Allylation of N-(Arylmethyl)sulfonimides with Allyl Grignard Reagents Involving Benzylic C-N Cleavage.

A new pair of reaction partners has been established for the aromatic C-H functionalization of benzyl electrophiles with nucleophiles via palladium-catalyzed benzylic C-N cleavage. A range of N-(1-naphthylmethyl)sulfonimides, N-(2-thienylmethyl)sulfonimides, and N-(2-furanylmethyl)sulfonimides smoothly underwent palladium-catalyzed aromatic C-H allylation with allyl Grignard reagents at room temperature, delivering structurally diverse substituted 1-allylnaphthalenes and 2-allylheteroarenes in moderate to excellent yields with extremely high regioselectivities. Replacing the N-(arylmethyl)sulfonimide with an (arylmethyl)ammonium salt, an arylmethyl chloride, or an arylmethyl phosphate as the benzyl electrophile leads to a dramatic erosion of the regioselectivity.

Palladium-Catalyzed Highly Regioselective Aromatic Substitution of Benzylic Ammonium Salts with Amines.

An unprecedented aromatic substitution reaction of benzylic ammonium salts has been developed through palladium-catalyzed C-N bond cleavage. A range of primary and secondary amines participated in a palladium-catalyzed aromatic substitution reaction of benzylic ammonium salts, delivering sterically hindered aromatic amines in moderate to excellent yields with extremely high regioselectivity. Preliminary mechanistic studies permitted successful identification of π-benzylpalladium complexes and γ-vinyl allylic amines as key intermediates. This study paves the way for the use of benzylic ammonium salts in the aromatic substitution reactions.