Synthesis of Eupomatenoids by Three Consecutive Transition Metal Catalyzed Cross-Coupling Reactions

Six different eupomatenoids ( 1a–c , 1f–h ) were prepared from 2,3,5-tribromobenzofuran ( 2 ) in a concise and high-yielding synthetic sequence. The overall yields vary between 29 and 60% over four to six steps. Key to the success of the syntheses is the high regioselectivity achieved in three Pd(0)- and Ni(0)-catalyzed cross-coupling reactions which were conducted consecutively. The order of substitution at the benzofuran nucleus is C-2, C-5 and C-3.