Iron- or Palladium-Catalyzed Reaction Cascades Merging Cycloisomerization and Cross-Coupling Chemistry

A conceptually novel reaction cascade is presented, which allows readily available enynes to be converted into functionalized 1,3‐dienes comprising a stereodefined tetrasubstituted alkene unit; such compounds are difficult to make by conventional means. The overall transformation is thought to commence with formation of a metallacyclic intermediate that evolves via cleavage of an unstrained C−X bond in its backbone. This non‐canonical cycloisomerization process is followed by a cross‐coupling step, such that reductive C−C bond formation regenerates the necessary low‐valent metal fragment and hence closes an intricate catalytic cycle. The cascade entails the formation of two new C−C bonds at the expense of the constitutional C−X entity of the substrate: importantly, the extruded group X must not be a heteroelement (X=O, NR), since activated β‐C−C bonds can also be broken. This concern was reduced to practice in two largely complementary formats: one procedure relies on the use of alkyl‐Grignard reagents in combination with catalytic amounts of Fe(acac)3, whereas the second method amalgamates cycloisomerization with Suzuki coupling by recourse to arylboronic acids and phosphine‐ligated palladium catalysts