Enantioselective Vinylogous Amination of 5-Alkyl-4-nitroisoxazoles with a Dipeptide-Based Guanidinium Phase-Transfer Catalyst.

An enantioselective vinylogous amination of 5-alkyl-4-nitroisoxazoles is reported. With a novel chiral dipeptide-based urea-amide-guanidinium as the phase-transfer catalyst, the reactions worked efficiently with NaOAc as the base, affording valuable and challenging-to-synthesize chiral isoxazole derivatives featuring a single stereocenter at the α-position in high yields and with excellent enantioselectivities. Theoretical studies with DFT predicted that cooperative multiple hydrogen-bonding and ion pairing interactions of a nucleophile and NaOAc with the catalyst is crucial to deprotonation by reducing their HOMO-LUMO energy gap.