Use of .beta.-sulfonyl vinyl ketones as equivalents to vinyl ketones in the Robinson annelation. Convergent, highly stereoselective preparation of a hydrindanol related to vitamin D from 2-methylcyclopent-2-enone and lithiated (E)-but-2-enyldiphenylphosphine oxide

Abstract

Conjugate addition of lithiated (E)-but-2-enyldiphenylphosphine oxide (3) to 2-methylcyclopent-2-enone (2) in tetrahydrofuran at -20 °C generates the enolate 8, which reacts rapidly with a series of β-sulfony1 vinyl ketones to generate unsaturated diketones in good yields. Hydrogenation of the latter products under medium pressure followed by aldol ring closure of the resulting δ-diketones generates hydrindenones equivalent to those obtained by Robinson annelation. The hydrindenones are stereoselectively converted by diisobutylaluminum hydride in dichloromethane into β-hydrindenols. The functionalized hydrindenone 15 prepared by the foregoing method from the dioxanylethyl β-sulfonyl vinyl ketone 5, upon hydrogenation under high pressure, gives with 95% stereoselectivity the trans-hydrindanone 20. This is converted by the Homer-Wittig reaction with α-methacrolein into the diene 26, hydrogenation of the β-epimer 26a of which provides the hydrindanol 27 bearing the alkyl side chain and the correct relative configuration at C13, C14, C17, and C20 of vitamin D.