The enantioselective 1,3-dipolar cycloaddition of nitrones and arylpropionaldehydes to generate highly functionalized scaffolds for application in drug discovery was herein investigated. The use of a second-generation MacMillan catalyst as hydrochloride salt consistently accelerated the reaction speed, allowing a decrease in the reaction time up to >100 times, still affording 4-isoxazolines with good to excellent enantiomeric ratios at room temperature. As a proof of concept, further functionalization of the isoxazoline core through Pd-catalyzed cross-coupling was performed, generating differently functionalized chemical architectures in high yield.

Fast MacMillan's Imidazolidinone-Catalyzed Enantioselective Synthesis of Polyfunctionalized 4-Isoxazoline Scaffolds

Dario Corbisiero
Primo
Investigation
;
Tommaso Fantoni
Investigation
;
Lucia Ferrazzano
Secondo
Conceptualization
;
Giulia Martelli
Visualization
;
Paolo Cantelmi
Writing – Review & Editing
;
Alexia Mattellone
Investigation
;
Chiara Palladino
Investigation
;
Magda Monari
Methodology
;
Riccardo Pedrazzani
Investigation
;
Alessandra Tolomelli
Penultimo
Conceptualization
;
Walter Cabri
Ultimo
Conceptualization
2022

Abstract

The enantioselective 1,3-dipolar cycloaddition of nitrones and arylpropionaldehydes to generate highly functionalized scaffolds for application in drug discovery was herein investigated. The use of a second-generation MacMillan catalyst as hydrochloride salt consistently accelerated the reaction speed, allowing a decrease in the reaction time up to >100 times, still affording 4-isoxazolines with good to excellent enantiomeric ratios at room temperature. As a proof of concept, further functionalization of the isoxazoline core through Pd-catalyzed cross-coupling was performed, generating differently functionalized chemical architectures in high yield.
Dario Corbisiero, Tommaso Fantoni, Lucia Ferrazzano, Giulia Martelli, Paolo Cantelmi, Alexia Mattellone, Chiara Palladino, Magda Monari, Riccardo Pedrazzani, Alessandra Tolomelli, Walter Cabri
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/899503
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