1161512-91-9Relevant academic research and scientific papers
Synthesis of 2-isoxazolines: Enantioselective and racemic methods based on conjugate additions of oximes
Pohjakallio, Antti,Pihko, Petri M.,Laitinen, Ulla M.
supporting information; experimental part, p. 11325 - 11339 (2010/11/16)
The formation of 3-unsubstituted 2-isoxazolines by means of condensation reactions between α,β-unsaturated aldehydes and oximes proceeds readily in the presence of catalytic amounts of anilinium salts. Mechanistically, the process involves a fast conjugate addition of the oxime and a slower intramolecular oxime-transfer reaction. The rate of oxime transfer was found to correlate with the acidity of the catalyst. This finding enabled us to discover an enantioselective process in which the fragile conjugate-addition product generated in the first stage is rapidly cyclized into the stable isoxazo-line under acidic conditions, with conservation of enantiomeric excess. In summary, herein we describe synthetically useful protocols for accessing 3-unsubstituted 2-isoxazolines in both the enantioselective and racemic manner. The mechanism of the condensation reaction catalyzed by the anilinium salt was also investigated by NMR spectroscopy experiments in which the effect of differently substituted aldehydes and oximes as well as water on the reaction rate was studied. The results point to the rate-limiting elimination of water from the 3-hydroxy-2-iso-xazolidine intermediate.
Base-catalyzed isomerization of 2-isoxazolines enables a two-step enantioselective synthesis of β-hydroxynitriles from enals
Pohjakallio, Antti,Pihko, Petri M.,Liu, Jun
scheme or table, p. 6712 - 6715 (2010/12/19)
The asymmetric synthesis of β-hydroxynitriles remains a challenge in organic synthesis. Herein we report a convenient synthesis of β-hydroxynitriles from enantiomerically enriched 3-unsubstituted 2-isoxazolines via a base-catalyzed ring-opening reaction that takes place without loss of enantiopurity. In combination with organocatalytic enantioselective synthesis of 3-unsubstituted 2-isoxazolines, the ring-opening enables a short 2-step synthesis of β-hydroxynitriles from α,β-unsaturated aldehydes in high enantiomeric purity.
Enantioselective synthesis of 2-isoxazolines by a One-flask conjugate addition/oxime-transfer process
Pohjakallio, Antti,Pihko, Petri M.
supporting information; experimental part, p. 3960 - 3964 (2009/11/30)
A study was conducted to demonstrate a new catalytic enantioselective method to prepare 5-substituted 2-isoxazolines that applied a small organic catalyst as the source of chirality and enabled the use of different α-β-unsaturated aldehydes as starting materials. The aldehyde and acetone oxime were added to a solution of amine and benzoic acid in toluene at 0 °C. A precooled solution of H2SO4 in MeOH was added and the resulting solution was stirred for 15 minutes at 0 °C after stirring the reaction mixture at 0 °C for the indicated period of time. A saturated aqueous solution of NaHCO3 was added and the mixture was extracted with EtOAc. The combined organic extracts were dried and concentrated, while the residue was purified by flash chromatography to afford the products. The results show that the presence of a strong acid in the reaction mixture induced the formation of similar catalytic species in the reactions.
