A copper/silver-mediated oxidative ortho-ethynylation of unactivated aryl CH bonds with terminal alkyne has been developed. The reaction uses the removable PIP directing group and features broad substrate scope, high functional-group tolerance, and compatibility with a wide range of heterocycles, providing an efficient synthesis of aryl alkynes. This procedure highlights the potential of copper catalysts to promote unique, synthetically enabling CH functionalization reactions that lie outside of the current scope of precious metal catalysis.

An improved and practical procedure for the stereoselective synthesis of anti-β-hydroxy-α-amino acids (anti-βhAAs), by palladium-catalyzed sequential C(sp³)H functionalization directed by 8-aminoquinoline auxiliary, is described. followed by a previously established monoarylation and/or alkylation of the β-methyl C(sp³)H of alanine derivative, β-acetoxylation of both alkylic and benzylic methylene C(sp³)H bonds affords various anti-β-hydroxy-α-amino acid derivatives. As an example, the synthesis of β-mercapto-α-amino acids, which are highly important to the extension of native chemical ligation chemistry beyond cysteine, is described. The synthetic potential of this protocol is further demonstrated by the synthesis of diverse β-branched α-amino acids. The observed diastereoselectivities are strongly influenced by electronic effects of aromatic AAs and steric effects of the linear side-chain AAs, which could be explained by the competition of intramolecular COAc bond reductive elimination from Pd^IV intermediates vs. intermolecular attack by an external nucleophile (AcO⁻) in an S_N2-type process.

A palladium-catalyzed arylation of unactivated γ-methylene C(sp³)H and remote δ-CH bonds by using an oxazoline-carboxylate directing group has been developed. Arylation occurs with a broad substrate scope and high tolerance of functional groups (i.e., halogen, nitro, cyano, ether, trifluoromethyl, amine, and ester). The oxazoline-type auxiliary can be removed under acidic conditions.

The alkylation of unactivated β-methylene C(sp³)H bonds of α-amino acid substrates with a broad range of alkyl iodides using Pd(OAc)₂ as the catalyst is described. The addition of NaOCN and 4-Cl-C₆H₄SO₂NH₂ was found to be crucial for the success of this transformation. The reaction is compatible with a diverse array of functional groups and proceeds with high diastereoselectivity. Furthermore, various β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-amino acids were prepared by sequential C(sp³)H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural β-disubstituted α-amino acids.

The alkylation of unactivated β-methylene C(sp³)H bonds of α-amino acid substrates with a broad range of alkyl iodides using Pd(OAc)₂ as the catalyst is described. The addition of NaOCN and 4-Cl-C₆H₄SO₂NH₂ was found to be crucial for the success of this transformation. The reaction is compatible with a diverse array of functional groups and proceeds with high diastereoselectivity. Furthermore, various β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-amino acids were prepared by sequential C(sp³)H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural β-disubstituted α-amino acids.