The synthesis of stereogenic quaternary carbons remains a significant challenge in organic synthesis. Alkaloid and terpene natural products containing such carbons embeded in a spiro[4.5]decane substructure are amongst the most difficult to synthesize. In this presentation we will discuss our on-going efforts to employ the Tsuji-Trost variant of the Winstein-Masamune (TTWM) intramolecular phenolic allylation in the context of total synthesis. The TTWM spirocyclization involves dearomatization and desymmetrization of a 4-substituted phenol derivative bearing an allylic carbonate to access the spiro[4.5]decane scaffold. We have been investigating the palladium catalyzed TTWM of phenols in the context of complex molecule synthesis. We are specifically interested in fawcettimine class lycopodium alkaloids such as magellanine, cyclopiane terpenes such as conidiogenone and the acorane terpene colletoic acid. We have demonstrated a six-step synthesis of dimethyl 8-oxo-4-vinylspiro[4.5]deca-6,9-diene-2,2-dicarboxylate from 4-hydroxybenzaldehyde as a platform to construct more complex tricylic molecular architectures. Elaboration of this substrate via the iodohydrin and subsequent treatment with tributylgermanium hydride effected a 5-exo-trig radical cyclization to afford model angular tricycles for alkaloid and terpene synthesis.

Spiro[4.5]cyclohexadienones as a platform for the synthesis of alkaloids and terpenes

254th National Meeting (2017)

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