Anti-Selective Catalytic Asymmetric Nitroaldol Reaction of α-Keto Esters: Intriguing Solvent Effect, Flow Reaction, and Synthesis of Active Pharmaceutical Ingredients

Tomoya Karasawa, Raphaël Oriez, Naoya Kumagai, Masakatsu Shibasaki

研究成果: Article査読

45 被引用数 (Scopus)

抄録

A rare-earth metal/alkali metal bimetallic catalyst proved particularly effective for enantioselectively coupling nitroalkanes and α-keto esters in an anti-selective manner to afford synthetically versatile, densely functionalized, and optically active α-nitro tertiary alcohols. A chiral diamide ligand captured two distinct metal cations, giving rise to a catalytically competent solid-phase heterobimetallic catalyst by simple mixing via self-assembly. The advantage of the solid-phase asymmetric catalyst was realized by successful application to the enantio- and diastereoselective reaction in a continuous-flow platform. The use of closely related solvents in terms of structures and polarity parameters, THF and its methylated congener 2-Me-THF, had an unexpectedly large solvent effect both on the reaction rate and the stereoselectivity. The nitroaldol products share a privileged unit for active pharmaceutical ingredients, as demonstrated by the streamlined enantioselective synthesis of the marketed antifungal agents efinaconazole and albaconazole.

本文言語English
ページ(範囲)12290-12295
ページ数6
ジャーナルJournal of the American Chemical Society
140
38
DOI
出版ステータスPublished - 2018 9月 26
外部発表はい

ASJC Scopus subject areas

  • 触媒
  • 化学一般
  • 生化学
  • コロイド化学および表面化学

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