Amide phosphonium salt catalyzed enantioselective Mannich addition of isoxazole-based nucleophiles to β,γ-alkynyl-α-ketimino esters

Abstract

An enantioselective Mannich addition of 3,5-disubstituted 4-nitroisoxazoles to β,γ-Alkynyl-α-ketimino esters promoted by amide phosphonium salt-based catalyst has been developed. N-Cbz-protected ketimino esters with various aryl substituents attached to alkyne unit...

Accessing unnatural α-amino acids with tetrasubstituted stereogenic centersviacatalytic enantioselective reactions of ketimine-type α-iminoesters/α-iminoamides

“…reported the enantioselective direct vinylogous Mannich-type reaction of acyclic ketimine-type α-iminoesters 47b with 5-methyl-4-nitro-isoxazoles as nucleophiles, with the reaction proceeding at the terminal carbon atom (Scheme 37). 64 This reaction is catalyzed by chiral amide phosphonium salt 92b to yield chiral ATAAs 96 with moderate-to-good enantioselectivities. The authors showed that the ester moiety in 47b plays an important activating role, as ketimines bearing trifluoromethyl groups instead of ester moieties do not react.…”

Copper-Catalyzed Direct Asymmetric Vinylogous Mannich Reaction between β,γ-Alkynyl-α-ketimino Esters and β,γ-Unsaturated N-Acylpyrazoles

“…Driven by our ongoing interest in asymmetric vinylogous-type reactions, we envisioned the asymmetric coupling of N-protected β,γ-alkynyl-α-ketimino esters with β,γ-unsaturated pyrazoleamides as a powerful platform for forging both desired motifs in one step. − While this strategy is intriguing, there are challenges related to regioselectivity and enantioselectivity control that must be addressed (Figure b). The regioselective addition of nucleophiles to alkynyl ketimino esters is challenging due to the presence of two potential electrophilic sites: the α-imino carbon atom and the γ-alkynyl carbon atom. , Conversely, the dienolate intermediates formed in situ from β,γ-unsaturated pyrazoleamides possess two potential nucleophilic sites (α- or γ-carbon).…”