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.