An Efficient Asymmetric Synthesis of 2-Substituted Ferrocenecarboxaldehydes

Ferrocenecarboxaldehyde is readily transformed into the acetal of (S)-1,2,4-butanetriol (1,3-dioxane structure) and further methylated to give acetal 15. This can then be ortho-lithiated using t-BuLi with very high diastereoselectivity (98% de). Electrophilic quenching provided a large array of compounds of established stereochemistry. Controlled hydrolysis leads to many ortho-substituted ferrocenecarboxaldehydes (98% ee) which themselves are starting materials in the synthesis of various classes of enantiopure ferrocene derivatives with planar chirality of predictable absolute configuration.