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.