Journalartikel
Autorenliste: Petrillo, Alexander; Kirchgessner-Prado, Kevin F.; Hiller, David; Eisenlohr, Kim A.; Rubin, Giacomo; Wuertele, Christian; Goldberg, Remy; Schatz, Dominic; Holthausen, Max C.; Garcia-Bosch, Isaac; Schindler, Siegfried
Jahr der Veröffentlichung: 2024
Zeitschrift: Journal of the American Chemical Society
ISSN: 0002-7863
eISSN: 1520-5126
DOI Link: https://doi.org/10.1021/jacs.4c07777
Verlag: American Chemical Society
Abstract:
Copper-mediated aromatic and aliphatic C-H hydroxylations using benign oxidants (O-2 and H2O2) have been studied intensively in recent years to meet the growing demand for efficient and green C-H functionalizations. Herein, we report an enantioselective variant of the so-called clip-and-cleave concept for intramolecular ligand hydroxylations by the application of chiral diamines as directing groups. We tested the hydroxylation of cyclohexanone and 1-acetyladamantane under different oxidative conditions (Cu-I/O-2; Cu-I/H2O2; Cu-II/H2O2) in various solvents. As an outstanding example, we obtained (R)-1-acetyl-2-adamantol with a yield of 37% and >99:1 enantiomeric excess from hydroxylation in acetone using Cu-I and O-2. Low-temperature stopped-flow UV-vis measurements in combination with density functional theory (DFT) computations revealed that the hydroxylation proceeds via a bis(mu-oxido) dicopper intermediate. The reaction product represents a rare example of an enantiopure 1,2-difunctionalized adamantane derivative, which paves the way for potential pharmacological studies. Furthermore, we found that 1-acetyladamantane can be hydroxylated in a one-pot reaction under air with isolated yields up to 36% and enantiomeric ratios of 96:4 using Cu-II/H2O2 in MeOH.
Zitierstile
Harvard-Zitierstil: Petrillo, A., Kirchgessner-Prado, K., Hiller, D., Eisenlohr, K., Rubin, G., Wuertele, C., et al. (2024) Expanding the Clip-and-Cleave Concept: Approaching Enantioselective C-H Hydroxylations by Copper Imine Complexes Using O2 and H2O2 as Oxidants, Journal of the American Chemical Society. https://doi.org/10.1021/jacs.4c07777
APA-Zitierstil: Petrillo, A., Kirchgessner-Prado, K., Hiller, D., Eisenlohr, K., Rubin, G., Wuertele, C., Goldberg, R., Schatz, D., Holthausen, M., Garcia-Bosch, I., & Schindler, S. (2024). Expanding the Clip-and-Cleave Concept: Approaching Enantioselective C-H Hydroxylations by Copper Imine Complexes Using O2 and H2O2 as Oxidants. Journal of the American Chemical Society. https://doi.org/10.1021/jacs.4c07777
Schlagwörter
ALIPHATIC HYDROXYLATION; MONOOXYGENASE
