C₂-Symmetric ligands

In

An early C₂-symmetric ligand, diphosphine catalytic ligand DIPAMP, was developed in 1968 by William S. Knowles and coworkers of Monsanto Company, who shared the 2001 Nobel Prize in Chemistry.^[2] This ligand was used in the industrial production of L-DOPA.

Some classes of C₂-symmetric ligands are called privileged ligands, which are ligands that are broadly applicable to multiple catalytic processes, not only a single reaction type.^[3][4]

• Ligands and Complexes
• 
  The C₂-symmetric

  diphosphine DIOP is historically significant.^[5]
• 
  DuPhos ligands are a class of C₂-symmetric ligands for asymmetric hydrogenation.^[6]
• 
  anticancer drug

  .
• 
  Jacobsen's epoxidation catalyst is a complex of a C₂-symmetric salen-type ligand.
• 
  C₂-symmetric diene ligand.^[7]
• 
  Both bi- and tridentate bis(oxazoline) ligands are used in organic synthesis
• 
  Both enantiomers of BINAP
• 
  BINOL

  , another binaphthalene-based ligand
• 
  TADDOL
• 
  DIPAMP, a diphosphine of historic significance
• 
  AD-mix α, dihydroquinine derivative used in Sharpless asymmetric dihydroxylation

Mechanistic concepts

While the presence of any symmetry element within a ligand intended for asymmetric induction might appear counterintuitive, asymmetric induction only requires that the ligand be chiral (i.e. have no improper rotation axis). Asymmetry (i.e. absence of any symmetry elements) is not required. C₂ symmetry improves the enantioselectivity of the complex by reducing the number of unique geometries in the transition states. Steric and kinetic factors then usually favor the formation of a single product.^[1][8]

Chiral fence

Chiral ligands work by

• Desimoni, G.; Faita, G.; Jorgensen, K. A. (2006). "C₂-Symmetric Chiral Bis(Oxazoline) Ligands in Asymmetric Catalysis". Chem. Rev. 106 (9): 3561–3651.
  PMID 16967916
  .
• Liu, X.; Lin, L.; Feng, X. (2011). "Chiral N,N'-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions". Acc. Chem. Res. 44 (8): 574–587.
  PMID 21702458
  .
• Evans, D. A.; Kozlowski, M. C.; Murry, J. A.; Burgey, C. S.; Campos, K. R.; Connell, B. T.; Staples, R. J. (1999). "C₂-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of Catalytic Enantioselective Aldol Additions of Enolsilanes to (Benzyloxy)Acetaldehyde". J. Am. Chem. Soc. 121 (4): 669–685.
  doi:10.1021/JA9829822
  .
• Gao, J.-X.; Ikariya, T.; Noyori, R. (1996). "A Ruthenium(II) Complex with a C₂-Symmetric Diphosphine/Diamine Tetradentate Ligand for Asymmetric Transfer Hydrogenation of Aromatic Ketones". Organometallics. 15 (4): 1087–1089.
  doi:10.1021/OM950833B
  .
• Pye, P. J.; Rossen, K.; Reamer, R. A.; Tsou, N. N.; Volante, R. P.; Reider, P. J. (1997). "New Planar Chiral Bisphosphine Ligand for Asymmetric Catalysis: Highly Enantioselective Hydrogenations under Mild Conditions". J. Am. Chem. Soc. 119 (26): 6207–6208.
  doi:10.1021/JA970654G
  .