Synthesis of (R)-Coniine and (S)-Coinicine via Organocatalytic α-Aminoxyl­ation of an Aldehyde

Abstract

A short and efficient synthesis of the indolizidine alkaloid (S)-coinicine has been achieved using organocatalytic sequential α-aminoxylation and Horner-Wadsworth-Emmons olefination of an aldehyde catalyzed by l-proline. Similarly, a common organocatalytic α-aminoxylation route has been developed for the asymmetric synthesis of both (R)-coniine and (S)-coinicine.

synthesis - organocatalysis - sequential reactions - proline - hemlock alkaloids

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<A NAME="RZ10510SS-12">12</A>

The enantiomeric excess (95% ee) was calculated using Mosher analysis by converting alcohol 8 into the monobenzylated alcohol 23 (Figure  [²] ) and then derivatizing alcohol 23 as its Mosher ester.

<A NAME="RZ10510SS-13">13</A>

The enantiomeric excess of 18 (95% ee) was calculated using Mosher analysis by derivatizing alcohol 18 as its Mosher ester.