Asymmetric Pentafulvene Carbometalation—Access to Enantiopure Titanocene Dichlorides of Biological Relevance

Unprecedented asymmetric copper‐catalyzed addition of ZnEt 2 (Z n Bu 2 ) to the exocyclic CC bond of pentafulvenes C 5 H 4 (CHAr) (Ar=2‐MeOPh and related species) results in enantiomerically enriched (up to 93:7 e.r.) cyclopentadienyl ligands (C 5 H 4 CHEtAr; abbreviated Cp R ). Copper catalyst promotion with both chiral phosphoramidite ligands and a phosphate additive is vital in realizing both acceptable enantioselectivities and reaction rates. Enantiomeric Cp R 2 TiCl 2 complexes have been prepared; the ( S , S ) isomer is twice as active towards pancreatic, breast, and colon cancer cell lines as its ( R , R ) enantiomer at 24 h.