Open AccessHighly Diastereoselective Functionalization of Piperidines by Photoredox-Catalyzed α-Amino C–H Arylation and Epimerization
Author(s) -
Morgan M. Walker,
Brian Koronkiewicz,
Shuming Chen,
K. N. Houk,
James M. Mayer,
Jonathan A. Ellman
Publication year - 2020
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.9b13165
Subject(s) - chemistry , diastereomer , piperidine , epimer , density functional theory , photochemistry , excited state , racemization , reaction mechanism , electron transfer , catalysis , medicinal chemistry , computational chemistry , stereochemistry , organic chemistry , physics , nuclear physics
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).