Enantioselective total synthesis of the unnatural enantiomer of quinine. Issue 41 (8th October 2019)

• Record Type: Journal Article
• Authors: Shiomi, Shinya; Misaka, Remi; Kaneko, Mayu; Ishikawa, Hayato
• Is Part Of: Chemical science. Volume 10:Issue 41(2019)
• Page Start: 9433
• Page End: 9437
• Publication Date: 2019-10-08
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9sc03879e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A practical enantioselective total synthesis of the unnatural (+)-quinine and (−)-9- epi -quinine enantiomers, which are important organocatalysts, is reported. 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.