Asymmetric pentafulvene carbometalation-access to enantiopure titanocene dichlorides of biological relevance

Cini, Melchior; Bradshaw, Tracey D.; Woodward, Simon; Lewis, William

Abstract

Unprecedented asymmetric copper-catalyzed addition of ZnEt2 (ZnBu2) to the exocyclic C[DOUBLE BOND]C bond of pentafulvenes C5H4([DOUBLE BOND]CHAr) (Ar=2-MeOPh and related species) results in enantiomerically enriched (up to 93:7 e.r.) cyclopentadienyl ligands (C5H4CHEtAr; abbreviated CpR). Copper catalyst promotion with both chiral phosphoramidite ligands and a phosphate additive is vital in realizing both acceptable enantioselectivities and reaction rates. Enantiomeric CpR2TiCl2 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.

Citation

Cini, M., Bradshaw, T. D., Woodward, S., & Lewis, W. (2015). Asymmetric pentafulvene carbometalation-access to enantiopure titanocene dichlorides of biological relevance. Angewandte Chemie International Edition, 54(47), https://doi.org/10.1002/anie.201508034

• Journal Article Type: Article
• Acceptance Date: Aug 26, 2015
• Online Publication Date: Oct 12, 2015
• Publication Date: Nov 16, 2015
• Deposit Date: Oct 14, 2016
• Publicly Available Date: Oct 14, 2016
• Journal: Angewandte Chemie International Edition
• Print ISSN: 1433-7851
• Electronic ISSN: 1521-3773
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 54
• Issue: 47
• DOI: https://doi.org/10.1002/anie.201508034
• Public URL: https://nottingham-repository.worktribe.com/output/766531
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/anie.201508034/full
• Additional Information: This is the peer reviewed version of the following article: Cini, M., Bradshaw, T. D., Woodward, S. and Lewis, W. (2015), Asymmetric Pentafulvene Carbometalation—Access to Enantiopure Titanocene Dichlorides of Biological Relevance. Angew. Chem. Int. Ed., 54: 14179–14182, which has been published in final form at http://dx.doi.org/10.1002/anie.201508034. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
• Contract Date: Oct 14, 2016