The synthesis of the novel Lewis acid, aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), and its use in the vinylogous aldol reaction between methyl crotonate and enolizable aldehydes are described. ATNP is related to Yamamoto’s Lewis acid, aluminum tris(2,6-diphenylphenoxide) (ATPH), but the 2-naphthyl groups more effectively block the α-position of aldehydes, enabling the selective enolization of crotonate esters in the presence of enolizable aldehydes. Vinylogous aldol reactions then proceed smoothly and in high yields with a variety of substrates.

The use of the intramolecular vinylogous aldol reaction for the preparation of an advanced intermediate for the synthesis of peloruside A is described. The reaction was applied to compound 19, and proceeds in high yield and good levels of diastereoselectivity. Application of the Achmatowicz reaction to this intermediate provided the corresponding pyranone, a late stage intermediate well positioned for conversion to the natural product.

Acid (I) generated in situ, promotes the reaction with various aldehydes including hindered, α‐branched and oxygenated ones.