Highly Diastereoselective Michael Additions onto Dienyl Bis-Sulfoxides

Abstract

An optimized procedure for the preparation of (S S ,S S)-bis(p-tolylsulfinyl)methane (4) is reported. Condensation of the lithium salt of 4 onto cinnamaldehyde furnished bis-sulfoxide dienyl derivative 5, a remarkable 1,4-Michael acceptor that can lead in a highly diastereoselective manner to vinylcyclopropyl adducts. In a chelating mode of reactivity using a methylcopper reagent, a complete reversal of stereoselectivity is observed giving an enantiopure b,g-unsaturated methyl ester intermediate that is used in the synthesis of cryptophycin.