Synthesis of a Vitamin D₃ Hydrindan Ring−Side-Chain Building Block, Involving Tandem Conjugate Addition and Alkylation Reactions

Abstract: Vitamin D₃ hydrindan ring−side-chain building block 4 (racemic) has been synthesized from ketene acetal 12 (derived from 6-methylheptanoic acid), 2-methylcyclopent-2-en-1-one (13), allyl methyl carbonate, and dimethyl methylphosphonate. The Mukaiyama−Michael conjugate addition of 12 and 13 yielded the adduct 11 (lk) accompanied by ca. 10% of its diastereomer. Allylation of 11 with allyl methyl carbonate in the presence of palladium catalyst afforded 10. The latter was transformed into enol lactone 26, which on treatment with 2 equiv of lithium dimethyl methylphosphonate and then 1 equiv of acetic acid provided 4.