Desymmetrization of aziridine with malononitrile using cinchona alkaloid amide/zinc(ii) catalysts

Abstract

The catalytic enantioselective desymmetrization of aziridines with malononitrile has been developed. Good yield and enantioselectivity were obtained by using cinchona alkaloid amide/Zn(ii) catalysts. The obtained product can be converted to β-aminoester, β-aminoamide and triamide compounds.

Recent developments in enantioselective zinc-catalyzed transformations

“…Earlier in 2017, Nakamura et al developed the first catalytic desymmetrization of protected aziridines 269 with malononitrile 270 using 12-24 mol% of a cinchona alkaloid zinc catalyst derived from ligand 271 and ZnEt 2 [126]. As illustrated in Scheme 91, the reaction of aziridines 269 having six-membered ring structures afforded by reaction with malononitrile 270 the corresponding chiral products 272 with high enantioselectivities (73-97% ee) and low to high yields (21-89%).…”

“…Scheme 91. Ring-opening reactions of aziridines with malononitrile in the presence of a cinchona alkaloid ligand[126].…”

Asymmetric Zinc Catalysis in Green One-pot Processes

“…Moreover, a range of aromatic, heteroaromatic and also aliphatic aldehydes provided, by reaction with o-anisidine and phenylacetylene, moderate to high enantioselectivities (68-97% ee). In 2017, Nakamura et al investigated for the first time the ringopening reaction of protected aziridines 121 with malononitrile 30 using 12-24 mol% of a cinchona alkaloid zinc catalyst derived from ligand 122 and ZnEt 2 (10-20 mol%) [70]. As illustrated in Scheme 33, acyclic aziridines 121 reacted with malononitrile 30 to give the corresponding ring-opened products 123 which subsequently underwent an intramolecular nucleophilic addition of the amide nitrogen to the cyano group to provide chiral 2,3-dihydro-1H-pyrrole products 124 in excellent enantioselectivities (90-94% ee) and good yields (64-75%).…”

Enantiodivergent Reaction of Ketimines with Malononitriles Using Single Cinchona Alkaloid Sulfonamide Catalysts

“…[7] Although pioneering studies have been conducted, expanding the scope of the catalytic enantioselective reaction of ketimines with malononitriles is highly desirable. We recently developed an enantioselective reaction of malononitrile with aziridines [8] and enantioselective reactions of ketimines with some nucleophiles. [9] Herein our ongoing interest has been extended to the enantiodivergent reaction of ketimines with malononitriles using chiral catalysts.…”