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

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.