Issue 41, 2019

Enantioselective total synthesis of the unnatural enantiomer of quinine

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.

Graphical abstract: Enantioselective total synthesis of the unnatural enantiomer of quinine

Associated articles

Supplementary files

Article information

Article type
Edge Article
Submitted
05 Aug. 2019
Accepted
19 Sept. 2019
First published
27 Sept. 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 9433-9437

Enantioselective total synthesis of the unnatural enantiomer of quinine

S. Shiomi, R. Misaka, M. Kaneko and H. Ishikawa, Chem. Sci., 2019, 10, 9433 DOI: 10.1039/C9SC03879E

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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