View source for Chemistry:C2-Symmetric ligands

{{Short description|Ligands that lack mirror symmetry but have two-fold rotational symmetry}}
{{DISPLAYTITLE:''C''<sub>2</sub>-Symmetric ligands}}
In [[Chemistry:Homogeneous catalysis|homogeneous catalysis]], '''''C''<sub>2</sub>-symmetric ligands''' refer to [[Chemistry:Ligand|ligand]]s that lack mirror symmetry but have [[Chemistry:Molecular symmetry|''C''<sub>2</sub> symmetry]] (two-fold rotational symmetry). Such ligands are usually [[Chemistry:Denticity|bidentate]] and are valuable in [[Chemistry:Catalysis|catalysis]].<ref name=Whitesell>{{cite journal|title=''C''<sub>2</sub> Symmetry and Symmetric Induction|author=James K. Whitesell|journal=Chem. Rev.|year=1989|volume=89|issue=7|pages=1581–1590|doi=10.1021/cr00097a012}}</ref> The ''C''<sub>2</sub> symmetry of ligands limits the number of possible reaction pathways and thereby increases enantioselectivity, relative to asymmetrical analogues. ''C''<sub>2</sub>-symmetric ligands are a subset of chiral ligands. Chiral ligands, including ''C''<sub>2</sub>-symmetric ligands, combine with metals or other groups to form chiral catalysts. These catalysts engage in [[Physics:Enantioselective synthesis|enantioselective chemical synthesis]], in which chirality in the catalyst yields chirality in the reaction product. 

==Examples==
An early ''C''<sub>2</sub>-symmetric ligand, [[Chemistry:Diphosphane|diphosphine]] catalytic ligand [[Chemistry:DIPAMP|DIPAMP]], was developed in 1968 by [[Biography:William Standish Knowles|William S. Knowles]] and coworkers of Monsanto Company, who shared the 2001 Nobel Prize in Chemistry.<ref>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 }}</ref> This ligand was used in the industrial production of [[Chemistry:L-DOPA|{{sc|L}}-DOPA]].

:[[File:L-dopaSyn.svg|thumb|center|550px|Synthesis of {{sc|L}}-DOPA via hydrogenation with ''C''<sub>2</sub>-symmetric diphosphine.]]

Some classes of ''C''<sub>2</sub>-symmetric ligands are called '''privileged ligands''', which are ligands that are broadly applicable to multiple catalytic processes, not only a single reaction type.<ref>{{cite journal | doi = 10.1073/pnas.0307152101 | volume=101 | title=Asymmetric Catalysis Special Feature Part II: Design of chiral ligands for asymmetric catalysis: From ''C''<sub>2</sub>-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 }}</ref><ref>{{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 }}</ref>

<gallery caption="Ligands and Complexes" mode=heights=102px>

(S,S)-DIOP.svg|The ''C''<sub>2</sub>-symmetric diphosphine [[Chemistry:DIOP|DIOP]] is historically significant.<ref>{{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.|last2 = Kagan|first2 = H. B.|journal = Journal of the Chemical Society D: Chemical Communications|issue = 10|pages = 481}}</ref>
DuPhos ligands.svg|DuPhos ligands are a class of ''C''<sub>2</sub>-symmetric ligands for [[Physics:Asymmetric hydrogenation|asymmetric hydrogenation]].<ref>{{cite journal|author1=Burk, M. J. |author2=Feaster, J. E. |author3=Nugent, W. A. |author4=Harlow, R. L. |title=Preparation and Use of ''C''<sub>2</sub>-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}}</ref>
Oxaliplatin-2D-skeletal.svg|[[Chemistry:Oxaliplatin|Oxaliplatin]], containing the ''C''<sub>2</sub>-symmetric [[Chemistry:Trans-1,2-Diaminocyclohexane|(''R'',''R'')-diaminocyclohexane]] ligand, is an important anticancer drug.
Jacobsen's catalyst (S,S).png|[[Chemistry:Jacobsen's catalyst|Jacobsen's epoxidation catalyst]] is a complex of a ''C''<sub>2</sub>-symmetric [[Chemistry:Salen ligand|salen-type ligand]].
HayashiChiralNBD.svg|''C''<sub>2</sub>-symmetric diene ligand.<ref>{{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}}</ref>
BOX and PyBOX.png|Both bi- and tridentate bis(oxazoline) ligands are used in [[Chemistry:Organic synthesis|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|[[Biology:TADDOL|TADDOL]]
DIPAMP.png|[[Chemistry:DIPAMP|DIPAMP]], a diphosphine of historic significance
(DHQ)2PHAL.png|[[Chemistry:AD-mix|AD-mix]] α, [[Chemistry:Dihydroquinine|dihydroquinine]] derivative used in [[Chemistry:Sharpless asymmetric dihydroxylation|Sharpless asymmetric dihydroxylation]]
</gallery>

==Mechanistic concepts==
While the presence of any symmetry element within a ligand intended for asymmetric induction might appear counterintuitive, [[Physics:Asymmetric induction|asymmetric induction]] only requires that the ligand be [[Biology:Chirality|chiral]] (i.e. have no [[Chemistry:Molecular symmetry#Elements|improper rotation axis]]). Asymmetry (i.e. absence of any [[Symmetry element|symmetry element]]s) is not required. ''C''<sub>2</sub> symmetry improves the enantioselectivity of the complex by reducing the number of unique geometries in the [[Chemistry:Transition state|transition state]]s. Steric and kinetic factors then usually favor the formation of a single product.<ref name=Whitesell/><ref>{{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}}</ref>
[[File:C2-symmetry in BOX ligands.png|thumb|center|400px|The left hand structure has a [[Chemistry:Molecular symmetry|''C''<sub>2</sub>‑rotational axis]] 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|400px|right|The chiral fence]]
Chiral ligands work by [[Physics:Asymmetric induction|asymmetric induction]] somewhere along the [[Chemistry:Reaction coordinate|reaction coordinate]]. The image to the right illustrates how a chiral ligand may induce an enantioselective reaction. The ligand (in green) has ''C''<sub>2</sub> 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 [[Chemistry:Acetophenone|acetophenone]] and the reagent (in blue) a [[Physics:Hydride|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'''.<ref>{{cite journal | doi = 10.1021/om00105a047 | volume=8 | title=Chiral and ''C''<sub>2</sub>-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 }}</ref> 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 ''C''<sub>2</sub>-symmetric complexes are known.  Some arise not from ''C''<sub>2</sub>-symmetric ligands, but from the orientation or disposition of high symmetry ligands within the coordination sphere of the metal.  Notably, [[Chemistry:EDTA|EDTA]] and triethylenetetraamine form complexes that are ''C''<sub>2</sub>-symmetric by virtue of the way the ligands wrap around the metal centers.  Two isomers are possible for (indenyl)<sub>2</sub>MX<sub>2</sub>, ''C''<sub>s</sub>- and ''C''<sub>2</sub>-symmetric.  The ''C''<sub>2</sub>-symmetric complexes are optically stable.

==Asymmetric ligands==
Ligands containing atomic chirality centers such [[Chemistry:Asymmetric carbon|asymmetric carbon]], which usually do not have ''C''<sub>2</sub>-symmetry, remain important in catalysis.  Examples include cinchona alkaloids and certain [[Chemistry:Phosphoramidite|phosphoramidite]]s. [[Chemistry:P-Chiral phosphine|P-chiral monophosphine]]s have also been investigated.

==See also==
* Chiral anion catalysis

==Further reading==
*{{cite journal| last1=Desimoni|first1=G.| last2=Faita|first2=G.| last3=Jorgensen|first3=K. A.|title=''C''<sub>2</sub>-Symmetric Chiral Bis(Oxazoline) Ligands in Asymmetric Catalysis | journal=Chem. Rev.|year=2006|volume=106|issue=9|pages=3561–3651|doi=10.1021/cr0505324|pmid=16967916}}
*{{cite journal| last1=Liu|first=X.| last2=Lin|first2=L.| last3=Feng|first3=X.|title=Chiral N,N'-Dioxides: New Ligands and Organocatalysts for Catalytic Asymmetric Reactions|journal=Acc. Chem. Res.|year=2011|volume=44|pages=574-587|issue=8|doi=10.1021/ar200015s| pmid=21702458}}
*{{cite journal| last1=Evans|first1=D. A.| last2=Kozlowski|first2=M. C.| last3=Murry|first3=J. A.| last4=Burgey|first4=C. S.| last5=Campos|first5=K. R.| last6=Connell|first6=B. T.| last7=Staples|first7=R. J.|title=''C''<sub>2</sub>-Symmetric Copper(II) Complexes as Chiral Lewis Acids. Scope and Mechanism of Catalytic Enantioselective Aldol Additions of Enolsilanes to (Benzyloxy)Acetaldehyde|journal=J. Am. Chem. Soc.|year=1999|volume=121|issue=4|doi=10.1021/JA9829822| pages=669–685}}
*{{cite journal| last1=Gao|first1=J.-X.| last2=Ikariya|first2=T.| last3=Noyori|first3=R.|title=A Ruthenium(II) Complex with a ''C''<sub>2</sub>-Symmetric Diphosphine/Diamine Tetradentate Ligand for Asymmetric Transfer Hydrogenation of Aromatic Ketones|journal=Organometallics|year=1996|volume=15|issue=4 |pages=1087–1089|doi=10.1021/OM950833B}}
*{{cite journal| last1=Pye|first1=P. J.| last2=Rossen|first2=K.| last3=Reamer|first3=R. A.| last4=Tsou|first4=N. N.| last5=Volante|first5=R. P.| last6=Reider|first6=P. J.|title=New Planar Chiral Bisphosphine Ligand for Asymmetric Catalysis: Highly Enantioselective Hydrogenations under Mild Conditions|journal=J. Am. Chem. Soc.|year=1997|volume=119|issue=26|pages=6207–6208|doi=10.1021/JA970654G}}

==References==
{{reflist|30em}}

{{Chiral synthesis}}

{{DEFAULTSORT:Chiral Ligand}}
[[Category:Coordination chemistry]]
[[Category:Stereochemistry]]
[[Category:Organometallic chemistry]]
[[Category:Ligands]]

{{Sourceattribution|C2-Symmetric ligands}}