Cobalt(III) Werner Complexes with 1,2-Diphenylethylenediamine Ligands: Readily Available, Inexpensive, and Modular Chiral Hydrogen Bond Donor Catalysts for Enantioselective Organic Synthesis

In the quest for new catalysts that can deliver single enantiomer pharmaceuticals and agricultural chemicals, chemists have extensively mined the “chiral pool”, with little in the way of inexpensive, readily available building blocks now remaining. It is found that Werner complexes based upon the D₃ symmetric chiral trication [Co­(en)₃]³⁺ (en = 1,2-ethylenediamine), which features an earth abundant metal and cheap ligand type, and was among the first inorganic compounds resolved into enantiomers 103 years ago, catalyze a valuable carbon–carbon bond forming reaction, the Michael addition of malonate esters to nitroalkenes, in high enantioselectivities and without requiring inert atmosphere conditions. The title catalysts, [Co­((S,S)-dpen)₃]³⁺ ((S,S)-3³⁺) 3X^–, employ a commercially available chiral ligand, (S,S)-1,2-diphenylethylenediamine. The rates and ee values are functions of the configuration of the cobalt center (Λ/Δ) and the counteranions, which must be lipophilic to solubilize the trication in nonaqueous media. The highest enantioselectivities are obtained with Λ and 2Cl^–BAr_f^–, 2BF₄^–BAr_f^–, or 3BF₄^– salts (BAr_f^– = B­(3,5-C₆H₃(CF₃)₂)₄^–). The substrates are not activated by metal coordination, but rather by second coordination sphere hydrogen bonding involving the ligating NH₂ groups. Crystal structures and NMR data indicate enthalpically stronger interactions with the NH moieties related by the C₃ symmetry axis, as opposed to those related by the C₂ symmetry axes; rate trends and other observations suggest this to be the catalytically active site. Both Λ- and Δ-(S,S)-3³⁺ 2Cl^–BAr_f^– are effective catalysts for additions of β-ketoesters to RO₂CNNCO₂R species (99–86% yields, 81–76% ee), which provide carbon–nitrogen bonds and valuable precursors to α-amino acids.