Reactivity study of the palladium cross-coupling synthesis of enediynes

Abstract

A reactivity study looking at various aspects of the palladium catalyzed (Sonogashira) reaction for die synthesis of enediynes was performed. Alkynes were coupled to 1,2- dichloro-, 1,2-dibromo- and 1,2-diiodobenzene. From this, four conclusions were drawn. It was determined that the carbon-iodine bond is die most reactive towards coupling though it is usually harder to obtain die second substitution in comparison to chlorine and bromine. It was found that alkynes bearing TMS and C(CH3)20H or moderately bulky (TBDMS, TIPS) groups couple to form disubstituted enediynes while alkynes containing THP do not. It was determined that this palladium cross-coupling reaction does not exhibit much if any solvent effect The order o f addition for die reaction mixture was only important if a reactive alkyne was used. In cases such as this, the alkyne should be added last to minimize homocoupling. Additionally, successful photochemical cyclizations were performed on three of the four enediynes syndiesized.