Oxidation-Induced β‑Selective C–H Bond Functionalization: Thiolation and Selenation of N‑Heterocycles

Site-selective intermolecular
C–H bond functionalization
is of central importance to synthetic chemistry. In particular, direct
β-functionalization of N-heterocycles still remains a great
challenge. Herein, we develop a strategy for oxidation-induced thiolation
and selenation at the β-position of piperidine derivatives and
1,2,3,4-tetrahydroisoquinoline via C–H bond functionalization.
Various 4-sulfenylisoquinolines, 3-sulfenylpyridines, and 4-selenylisoquinolines
can be obtained by using O2 as the only oxidant. Notably,
neither a directing group nor a metal catalyst is necessary in this
transformation. The preliminary mechanistic studies revealed that
the oxidation and rearrangement pathway were key steps in this transformation,
which provides a meaningful strategy for controlling site selectivity
in the β-functionalization of N-heterocycles.