Arylketone π-Conjugation Controls Enantioselectivity in Asymmetric Alkynylations Catalyzed by Centrochiral Ruthenium Complexes
- Resource Type
- Authors
- Yu Zheng; Tianjiao Cui; Shuming Chen; Eric Meggers; Kendall N. Houk
- Source
- Journal of the American Chemical Society. 140:5146-5152
- Subject
- chemistry.chemical_classification
Steric effects
Ketone
010405 organic chemistry
Acetylide
chemistry.chemical_element
General Chemistry
Propargyl alcohol
010402 general chemistry
01 natural sciences
Biochemistry
Asymmetric induction
Medicinal chemistry
Catalysis
Transition state
0104 chemical sciences
Ruthenium
chemistry.chemical_compound
Colloid and Surface Chemistry
chemistry
Intramolecular force
- Language
- ISSN
- 1520-5126
0002-7863
The origin of enantioselectivity in the asymmetric alkynylation of trihalomethyl ketones catalyzed by octahedral stereogenic-at-ruthenium complexes has been investigated through density functional theory calculations. Computational results support a mechanism involving formation of a ruthenium acetylide, followed by pre-coordination of the trihalomethyl ketone through the carbonyl oxygen and intramolecular attack of the acetylide via a compact four-membered transition state. Differences in computed free energies of activation for the formation of the major and minor propargyl alcohol enantiomers are in good agreement with the experimentally observed levels of asymmetric induction. Analysis of fragment distortion energies shows that disfavored transition states are destabilized due to the more severe distortion and loss of π-conjugation in the coordinated arylketone fragments. Examination of the different substitution patterns in the ketone substrate and the catalyst reveals the key steric factors that control the enantioselectivity. Finally, calculations indicate promising directions for the simplification of the catalyst scaffold while preserving the high levels of enantioselectivity of these alkynylation reactions.