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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Fast MacMillan's Imidazolidinone-Catalyzed Enantioselective Synthesis of Polyfunctionalized 4-Isoxazoline Scaffolds
Dario Corbisiero1, Tommaso Fantoni1, Lucia Ferrazzano1
1Department of Chemistry, Alma Mater Studiorum University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
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.
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