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Asymmetric Pentafulvene Carbometalation—Access to Enantiopure Titanocene Dichlorides of Biological Relevance
Author(s) -
Cini Melchior,
Bradshaw Tracey D.,
Woodward Simon,
Lewis William
Publication year - 2015
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201508034
Subject(s) - enantiopure drug , chemistry , phosphoramidite , cyclopentadienyl complex , enantiomer , stereochemistry , catalysis , enantioselective synthesis , medicinal chemistry , aldol reaction , combinatorial chemistry , organic chemistry , oligonucleotide , dna , biochemistry
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.