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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.

A Pd(II)-catalyzed protocol for highly regioselective distal γ-C–H silylation and germanylation of aliphatic carboxylic acids is reported. Bidentate 8-aminoquinoline as the directing group was found to stabilize the six-membered palladacycle. A variety of aliphatic carboxylic acids and amino acids were silylated and germanylated in good yields and high diasteroselectivities. Detailed mechanistic studies involving isolation of a Pd(II) intermediate, determination of the reaction rate and order, control experiments, and isotopic labeling and DFT studies were found to be crucial for elucidating the elementary steps involved in this distal aliphatic functionalization.