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

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.