Ligand-Enabled Auxiliary-Free meta-C-H Arylation of Phenylacetic Acids.

The meta-C-H arylation of free phenylacetic acid was realized using 2-carbomethoxynorbornene (NBE-CO2 Me) as a transient mediator. Both the modified norbornene and the mono-protected 3-amino-2-hydroxypyridine type ligand are crucial for this auxiliary-free meta-C-H arylation reaction. A series of phenylacetic acids, including mandelic acid and phenylglycine, react smoothly with various aryl iodides to provide the meta-arylated products in high yields.

Ligand-Enabled ß-C-H Arylation of α-Amino Acids Without Installing Exogenous Directing Groups.

Herein we report acid-directed ß-C(sp3 )-H arylation of α-amino acids enabled by pyridine-type ligands. This reaction does not require the installation of an exogenous directing group, is scalable, and enables the preparation of Fmoc-protected unnatural amino acids in three steps. The pyridine-type ligands are crucial for the development of this new C(sp3 )-H arylation.

Ligand-Promoted meta-C-H Amination and Alkynylation.

Using a modified norbornene (methyl bicyclo[2.2.1]hept-2-ene-2-carboxylate) as a transient mediator, meta-C-H amination and meta-C-H alkynylation of aniline and phenol substrates have been developed for the first time. Both the identification of a monoprotected 3-amino-2-hydroxypyridine/pyridone-type ligand and the use of a modified norbornene as a mediator are crucial for the realization of these two unprecedented meta-C-H transformations. A variety of substrates are compatible with both meta-C-H amination and meta-C-H alkynylation. Amination and alkynylation of heterocyclic substrates including indole, indoline, and indazole afford the desired products in moderate to high yields.

Ligand-Enabled Stereoselective ß-C(sp(3))-H Fluorination: Synthesis of Unnatural Enantiopure anti-ß-Fluoro-α-amino Acids.

A quinoline-based ligand was shown to promote palladium-catalyzed ß-C(sp(3))-H fluorination for the first time. A range of unnatural enantiopure fluorinated α-amino acids were obtained through sequential ß-C(sp(3))-H arylation and subsequent stereoselective fluorination from readily available L-alanine.