A Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis

Abstract

An expedient approach to the construction of arylated 2,6-cis-disubstituted dihydropyran framework was developed involving subsequent DDQ-mediated diastereoselective allylation at an oxygen-substituted benzylic position and ring-closing metathesis (RCM) as key transformations. The synthetic utility of the methodology was illustrated by a formal total synthesis of (±)-centrolobine in five steps from the known homoallylic alcohol or in eight steps from the readily available THP-protected glycidol. This route allows for direct access towards other diarylheptanoid natural products and their synthetic analogues with a variety of side chains.

Key words

total synthesis - centrolobine - diastereoselective allylation - ring-closing metathesis - 2,3-dichloro-5,6-dicyano-1,4-benzoquinone

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