Highly Diastereoselective Functionalization of Piperidines by Photoredox-Catalyzed α‑Amino C–H Arylation and Epimerization

We
report a photoredox-catalyzed α-amino C–H arylation
reaction of highly substituted piperidine derivatives with electron-deficient
cyano­(hetero)­arenes. The scope and limitations of the reaction were
explored, with piperidines bearing multiple substitution patterns
providing the arylated products in good yields and with high diastereoselectivity.
To probe the mechanism of the overall transformation, optical and
fluorescent spectroscopic methods were used to investigate the reaction.
By employing flash-quench transient absorption spectroscopy, we were
able to observe electron transfer processes associated with radical
formation beyond the initial excited-state Ir­(ppy)3 oxidation.
Following the rapid and unselective C–H arylation reaction,
a slower epimerization occurs to provide the high diastereomer ratio
observed for a majority of the products. Several stereoisomerically
pure products were resubjected to the reaction conditions, each of
which converged to the experimentally observed diastereomer ratios.
The observed distribution of diastereomers corresponds to a thermodynamic
ratio of isomers based upon their calculated relative energies using
density functional theory (DFT).