An Iron-Catalyzed Bond-Making/Bond-Breaking Cascade Merges Cycloisomerization and Cross-Coupling Chemistry

Treatment of readily available enynes with alkyl‐Grignard reagents in the presence of catalytic amounts of Fe(acac)3 engenders a remarkably facile and efficient reaction cascade that results in the net formation of two new C−C bonds while a C−Z bond in the substrate backbone is broken. Not only does this new manifold lend itself to the extrusion of heteroelements (Z=O, NR), but it can even be used for the cleavage of activated C−C bonds. The reaction likely proceeds via metallacyclic intermediates, the iron center of which gains ate character before reductive elimination occurs. The overall transformation represents a previously unknown merger of cycloisomerization and cross‐coupling chemistry. It provides ready access to highly functionalized 1,3‐dienes comprising a stereodefined tetrasubstituted alkene unit, which are difficult to make by conventional means. Cut and paste: Iron catalysis allows cycloisomerization chemistry and cross‐coupling to be merged into a new reaction cascade. This manifold engenders formation of two new C−C bonds at the expense of a C−Z bond in the substrate backbone, which is cleaved while the tetrasubstituted alkene product is forming.