Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones
Pooja Goyal1,2, Akhil K Dubey1, Raghunath Chowdhury1,2
1Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085, India.
Abstract:
The enantioselective 1,4-addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones catalyzed by a cinchona alkaloid-derived primary amine-Brønsted acid composite is reported. Both enantiomers of the anticipated pyrazole derivatives were obtained in good to excellent yields (up to 97%) and high enantioselectivities (up to 98.5% ee) under mild reaction conditions. In addition, this protocol was further expanded to synthesize highly enantioenriched hybrid molecules bearing biologically relevant heterocycles.
Related Concept Videos
Conjugate Addition of Enolates: Michael Addition
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
α-Alkylation of Ketones via Enolate Ions
Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...


