Development of a Chiral N -Alkoxyamide Strategy and Application to the Asymmetric Total Synthesis of Fasicularin

Ryo Minamikawa, Keisuke Fukaya, Akihiro Kobayashi, Yukinori Komiya, Shio Yamamoto, Daisuke Urabe, Noritaka Chida, Takaaki Sato

Research output: Contribution to journalArticlepeer-review

Abstract

The asymmetric total synthesis of fasicularin by a chiral N -alkoxyamide strategy is reported. Incorporation of the chiral alkoxy group onto an amide nitrogen changes the original reactivity of the amide, enabling two key transformations: aza-spirocyclization and the reductive Strecker reaction. DFT calculations indicate that pyramidalization of the N -alkoxyamide nitrogen is crucial to produce a cyclic hemiaminal in equilibrium, which undergoes aza-spirocyclization. The chiral alkoxy group is also used as a stereocontrol element to establish two consecutive stereocenters. The iridium-catalyzed reductive Strecker reaction of the N -alkoxylactam provides the aminonitrile with high diastereoselectivity.

Original languageEnglish
JournalSynthesis (Germany)
DOIs
Publication statusAccepted/In press - 2021

Keywords

  • amides
  • DFT calculations
  • fasicularin
  • heteroatom-heteroatom bonds
  • nucleophilic addition
  • remote stereocontrol
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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