A -Methoxy-y-pyrone scaffold

Present in several natural products, the a -methoxy-y-pyrone scaffold (Fig. 2) is an aromatic motif whose preparation is far from trivial, as illustrated by the known procedures demonstrating both moderate efficiency for the cyclization and regioselectivity for the alkylation. 

To bring simplicity, safety, and convergence to the synthesis of such motifs, we envisioned a novel strategy comprising nucleophilic 1,4-addition to a,a -dimethoxy-y-pyrone 7 (Scheme 4). Overall, this transformation would result in a desymmetrization of 7 that would not only enable the synthesis of the a -methoxy-y-pyrone scaffold but also the grafting of the side chain, providing a short and convergent route to products such as 8. 

Conjugate addition of a nucleophile to 7 would afford the adduct 9, a versatile pronucleophUe containing the a -methoxy-y-pyrone scaffold (Scheme 5). After deprotonation, vinylogous enolate 9 could react with an electrophile, modulable according to the desired target, providing the elaborated compoimd 10 in one pot. 

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