Organocatalyzed Highly Enantioselective Aldol Reaction of Aldehydes for Synthesis of ( R )‐Pantolactone

作者：Zhi‐Hong Du, Meng Yuan, Bao‐Xiu Tao, Wen‐Juan Qin, Xiangming Liang, Yu‐Yan Li, Hang Lin, L Zhang, Chao‐Shan Da · 发表于：Asian Journal of Organic Chemistry · 年份：2021 · DOI：10.1002/ajoc.202100106 · 被引用次数：7 · 研究领域：Carbohydrate Chemistry and Synthesis、Asymmetric Synthesis and Catalysis、Synthetic Organic Chemistry Methods

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.