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Organocatalyzed Highly Enantioselective Aldol Reaction of Aldehydes for Synthesis of ( R )‐Pantolactone
Author(s) -
Du ZhiHong,
Yuan Meng,
Tao BaoXiu,
Qin WenJuan,
Liang XiangMing,
Li YuYan,
Lin Hang,
Zhang LianChun,
Da ChaoShan
Publication year - 2021
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.202100106
Subject(s) - chemistry , aldol reaction , glyoxylate cycle , enantioselective synthesis , moiety , aldehyde , yield (engineering) , organic chemistry , electrophile , amide , catalysis , stereochemistry , enzyme , materials science , metallurgy
Abstract This work demonstrates that a tert ‐leucine‐derived 2‐phenolic anilide is the efficient organocatalyst to catalyze the asymmetric cross‐aldol reaction of glyoxylate and alkyl aldehydes in high yield and enantioselectivity at room temperature. As compared to the reported simple primary amino acids, the 2‐phenolic anilide can produce two hydrogen bonds from its phenolic hydroxy and amide groups with aldehyde moiety of ethyl glyoxylate, greatly enhancing the electrophilicity of ethyl glyoxylate and effectively increasing the asymmetric induction of the aldol reaction. Additionally, the large side group‐bearing tert ‐leucine is also essential to high enantioselectivity. The reaction was successfully performed on 50 mmol scale with no decrease in the yield and enantioselectivity, showing potential for the chemical production of the pharmaceutical intermediate ( R )‐pantolactone with high yield and enantiopurity in an eco‐friendly method.