Enantioselective total synthesis of the unnatural enantiomer of quinine

Shinya Shiomi, Remi Misaka, Mayu Kaneko, Hayato Ishikawa

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8 Citations (Scopus)

Abstract

A practical enantioselective total synthesis of the unnatural (+)-quinine and (-)-9-epi-quinine enantiomers, which are important organocatalysts, is reported. The key transformation is a successive organocatalytic formal aza [3 + 3] cycloaddition/Strecker-type cyanation reaction to form an optically active tetrasubstituted piperidine derivative. This organocatalytic reaction proceeded in high yield and gave excellent enantiomeric excess with only 0.5 mol% catalyst loading. In addition, an imidate group, derived from a cyano group, was incorporated in the strategy for site-selective modification of the C4-alkyl chiral piperidine ring of quinine. Furthermore, an efficient coupling between the quinuclidine precursor and dihydroquinoline unit was achieved on a gram scale. The 15-step (LLS) synthetic protocol provided both (+)-quinine and (-)-9-epi-quinine, each with 16% overall yield.

Original languageEnglish
Pages (from-to)9433-9437
Number of pages5
JournalChemical Science
Volume10
Issue number41
DOIs
Publication statusPublished - 2019
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)

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