Syntheses of Werner complexes: Applications as chiral hydrogen bond donors in enantioselective catalysis

Coordination compounds with 1,2-ethylenediamine (en) ligands have played vital roles in the development of inorganic chemistry and stereochemistry. Nobel laureate Alfred Werner synthesized and resolved both enantiomers of [Co(en)3]3+ into their respective Λ and Δ forms over a century ago. Despite this rich background, these complexes have remained dormant in terms of synthetic utility until recently. This is largely due to the strong field amine ligands that are difficult to displace and their low spin d6 electron configuration, rendering these octahedral complexes kinetically substitution inert. Conversely, these attributes, in addition to the quantity and quality of NH units, lend Werner complexes to serve as effective chiral H-bond donating catalysts, featuring potential applications in the synthesis of pharmaceuticals and agrichemicals. Central to this goal are the anion metathesis reactions conducted for the substitution of commonly paired halide anions with lipophilic anions. These reactions enhance the solubility of the complexes in organic solvents and decrease the competition between anions and substrates for NH donor sites. Amongst the latest discoveries, lipophilic cobalt cage complexes have led us to deduce that high enantioselectivity is predicated on the substrates’ ability to hydrogen bond with the C3 faces of the catalysts. Additionally, the variation of [M(en)3]n+ to include Mn+ = Cr3+, Rh3+, Ir3+, and Pt4+ has furnished complexes with variable thermal stabilities. Finally, the ligands have been further decorated with functionalized phenyl rings via simple, stereospecific synthetic routes resulting in catalysts with a breadth of steric bulk, NH unit acidities, and solubility profiles.