Catalysis

Valine

Enantioselective synthesis

Amino acid

Leucine

Desymmetrization

Biochemistry

Stereochemistry

Combinatorial chemistry

Organic chemistry

Isoleucine

Regioselectivity

Chemistry

Carboxylic acid

Moiety

ACS Catalysis

A Pd(II)-catalyzed highly regioselective γ-chalcogenation, thioarylation, and selenoarylation of aliphatic carboxylic acids has been demonstrated. The present protocol provides a direct access to make structural modifications of α-amino acids such as valine, isoleucine, and tert-leucine with high diastereoselectivity (up to 52:1). Sequential heterobifunctionalizations have been carried out at γ-sp3 C–Hs, resulting in desymmetrization of quaternary centers. The applicative potential of the chalcogenated products was exhibited by using them as precursors for the synthesis of the biologically relevant benzothiepinone moiety. Preliminary studies were carried out to gain insights into the mechanism.

Promoting Highly Diastereoselective γ-C–H Chalcogenation of α-Amino Acids and Aliphatic Carboxylic Acids