C2-Symmetric ligands

{{Short description|Ligands that lack mirror symmetry but have two-fold rotational symmetry}}

In homogeneous catalysis, C₂-symmetric ligands refer to ligands that lack mirror symmetry but have C₂ symmetry (two-fold rotational symmetry). Such ligands are usually bidentate and are valuable in catalysis.{{cite journal|title=C₂ Symmetry and Symmetric Induction|author=James K. Whitesell|journal=Chem. Rev.|year=1989|volume=89|issue=7|pages=1581–1590|doi=10.1021/cr00097a012}} The C₂ symmetry of ligands limits the number of possible reaction pathways and thereby increases enantioselectivity, relative to asymmetrical analogues. C₂-symmetric ligands are a subset of chiral ligands. Chiral ligands, including C₂-symmetric ligands, combine with metals or other groups to form chiral catalysts. These catalysts engage in enantioselective chemical synthesis, in which chirality in the catalyst yields chirality in the reaction product.

Examples

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.Nobel prize 2001 www.nobelprize.org [https://nobelprize.org/nobel_prizes/chemistry/laureates/2001/public.html Link] {{webarchive|url=https://web.archive.org/web/20070713055723/https://nobelprize.org/nobel_prizes/chemistry/laureates/2001/public.html |date=2007-07-13 }} This ligand was used in the industrial production of L-DOPA.

:File:L-dopaSyn.svg

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.{{cite journal | doi = 10.1073/pnas.0307152101 | volume=101 | title=Asymmetric Catalysis Special Feature Part II: Design of chiral ligands for asymmetric catalysis: From C₂-symmetric P,P- and N,N-ligands to sterically and electronically nonsymmetrical P,N-ligands | year=2004 | journal=Proceedings of the National Academy of Sciences | pages=5723–5726 | last1 = Pfaltz | first1 = A.| issue=16 | doi-access=free | pmid=15069193 | pmc=395974 | bibcode=2004PNAS..101.5723P }}{{cite journal | doi = 10.1126/science.1083622 | pmid = 12637734 | volume=299 | title=Privileged chiral catalysts | date=March 2003 | journal=Science | pages=1691–3 | last1 = Yoon | first1 = TP | last2 = Jacobsen | first2 = EN| issue = 5613 | bibcode = 2003Sci...299.1691Y | s2cid = 27416160 }}

(S,S)-DIOP.svg|The C₂-symmetric diphosphine DIOP is historically significant.{{cite journal|doi = 10.1039/C29710000481|title = The asymmetric synthesis of hydratropic acid and amino-acids by homogeneous catalytic hydrogenation|year = 1971|last1 = Dang|first1 = T. P.|author2-link = Henri B. Kagan|last2 = Kagan|first2 = H. B.|journal = Journal of the Chemical Society D: Chemical Communications|issue = 10|pages = 481}}

DuPhos ligands.svg|DuPhos ligands are a class of C₂-symmetric ligands for asymmetric hydrogenation.{{cite journal|author1=Burk, M. J. |author2=Feaster, J. E. |author3=Nugent, W. A. |author4=Harlow, R. L. |title=Preparation and Use of C₂-Symmetric Bis(Phospholanes): Production of a-Amino Acid Derivatives Via Highly Enantioselective Hydrogenation Reactions|journal=J. Am. Chem. Soc.|year=1993|volume=115|pages=10125–10138|doi=10.1021/ja00075a031}}

Oxaliplatin-2D-skeletal.svg|Oxaliplatin, containing the C₂-symmetric (R,R)-diaminocyclohexane ligand, is an important anticancer drug.

Jacobsen's catalyst (S,S).png|Jacobsen's epoxidation catalyst is a complex of a C₂-symmetric salen-type ligand.

HayashiChiralNBD.svg|C₂-symmetric diene ligand.{{cite journal|author1=Hayashi, T. |author2=Ueyama, K. |author3=Tokunaga, N. |author4=Yoshida, K. |title=A Chiral Chelating Diene as a New Type of Chiral Ligand for Transition Metal Catalysts: Its Preparation and Use for the Rhodium-Catalyzed Asymmetric 1,4-Addition|journal=J. Am. Chem. Soc.|year=2003|volume=125|issue=38|pages=11508–11509|doi=10.1021/ja037367z|pmid=13129348|bibcode=2003JAChS.12511508H }}

BOX and PyBOX.svg|Both bi- and tridentate bis(oxazoline) ligands are used in organic synthesis

BINAP Enantiomers Structural Formulae V.1.svg|Both enantiomers of BINAP

R-BINOL-2D-skeletal.png|BINOL, another binaphthalene-based ligand

TADDOLgeneric.png|TADDOL

DIPAMP.svg|DIPAMP, a diphosphine of historic significance

(DHQ)2PHAL.png|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.{{cite journal|last=Rasappan|first=Ramesh|author2=Laventine, Dominic |author3=Reiser, Oliver |title=Metal-bis(oxazoline) complexes: From coordination chemistry to asymmetric catalysis|journal=Coordination Chemistry Reviews|year=2008|volume=252|issue=5–7|pages=702–714|doi=10.1016/j.ccr.2007.11.007}}

File:C2-symmetry in BOX ligands.png whereas the right hand structure is asymmetric. Arrows indicate the proposed trajectories for attack by substrates, identical colours lead to identical transition states (and hence products) with red arrows being disfavoured due to steric repulsion.]]

=Chiral fence=

:Image:ChiralLigandsInnerWorkings.png

Chiral ligands work by asymmetric induction somewhere along the reaction coordinate. The image to the right illustrates how a chiral ligand may induce an enantioselective reaction. The ligand (in green) has C₂ symmetry with its nitrogen, oxygen or phosphorus atoms hugging a central metal atom (in red). In this particular ligand the right side is sticking out and its left side points away. The substrate in this reduction is acetophenone and the reagent (in blue) a hydride ion. In absence of the metal and the ligand the Re face approach of the hydride ion gives the (S)-enantiomer and the Si face approach the (R)-enantiomer in equal amounts (a racemic mixture like expected). The ligand and metal presence changes all that. The carbonyl group will coordinate with the metal and due to the steric bulk of the phenyl group it will only be able to do so with its Si face exposed to the hydride ion with in the ideal situation exclusive formation of the (R) enantiomer. The re face will simply hit the chiral fence.{{cite journal | doi = 10.1021/om00105a047 | volume=8 | title=Chiral and C₂-symmetrical bis(oxazolinylpyridine)rhodium(III) complexes: effective catalysts for asymmetric hydrosilylation of ketones | year=1989 | journal=Organometallics | pages=846–848 | last1 = Hisao | first1 = Nishiyama| issue=3 }} Note that when the ligand is replaced by its mirror image the other enantiomer will form and that a racemic mixture of ligand will once again yield a racemic product. Also note that if the steric bulk of both carbonyl substituents is very similar the strategy will fail.

Other ''C''<sub>2</sub>-symmetric complexes

Many C₂-symmetric complexes are known. Some arise not from C₂-symmetric ligands, but from the orientation or disposition of high symmetry ligands within the coordination sphere of the metal. Notably, EDTA and triethylenetetraamine form complexes that are C₂-symmetric by virtue of the way the ligands wrap around the metal centers. Two isomers are possible for (indenyl)₂MX₂, C_s- and C₂-symmetric. The C₂-symmetric complexes are optically stable.

Asymmetric ligands

Ligands containing atomic chirality centers such asymmetric carbon, which usually do not have C₂-symmetry, remain important in catalysis. Examples include cinchona alkaloids and certain phosphoramidites. P-chiral monophosphines have also been investigated.

References

Category:Coordination chemistry

Category:Stereochemistry

Category:Organometallic chemistry

Category:Ligands