Organocatalyst-mediated five-pot synthesis of (-)-quinine.

Terunuma, Takahiro; Hayashi, Yujiro · Nat Commun · 2022

basic_science · Level V

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Abstract

In this work, the enantioselective total synthesis of (-)-quinine has been accomplished in a pot-economical manner using five reaction vessels. In the first pot, reactions involve the diphenylprolinol silyl ether-mediated Michael reaction, aza-Henry reaction, hemiaminalization, and elimination of HNO<sub>2</sub> (five reactions), affording a chiral tetrahydropyridine with excellent enantioselectivity. In the second pot, five reactions proceed with excellent diastereoselectivity to afford a trisubstituted piperidine with the desired stereochemistry. A further five reactions are carried out in the last one-pot sequence.

Medical subject headings