chiral concave n-heterocyclic carbenes 3 rd international summer school “supramolecular systems in...
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Chiral ConcaveN-Heterocyclic Carbenes
3rd International Summer School“Supramolecular Systems in Chemistry and Biology“
Tim ReimersKiel, GER
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N-Heterocyclic Carbenes (NHC)
Different ring sizes…Different heteroatoms…
Bulky groups R are needed to avoid dimerization
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How to make NHCs?
E.g. by deprotonation:
First crystalline carbene (1991)!
A. J. Arduengo III, R. L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361.
Ad = Adamantyl
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What can NHCs be used for?
As ligands in transition metal mediated reactions:
Olefin metathesisSuzuki-Miyaura reaction
M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 6, 953.O. Navarro, R. A. Kelly III, S. P. Nolan, J. Am. Chem. Soc. 2003, 125, 16194.
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What can NHCs be used for?
As organocatalysts:
C. Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205.
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What does “concave“ mean?
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A Concave Catalyst
Concave system
Reactive centre
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A Concave Catalyst
Concave system
Reactive centre
Solvent
Substrate
Functional group
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Turn over number?
A Concave Catalyst
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A Concave Catalyst
Concavebimacrocyclic
NHC
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Special Effect with a Concave NHC
52 %
X = (CH2)8
41 %
X = (CH2)10
3 %
n. o.
n. o.
42 %
O. Winkelmann, C. Näther, U. Lüning, Org. Biomol. Chem. 2009, 7, 553.
* * * *
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Chiral Concave NHC
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Chiral Concave NHC
Problem: Interconversion by rotation at room temperature
Chiral resolution impossible!
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NMR Experiments
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
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NMR Experiments
CDCl3
C2D2Cl4
CD2Cl2
C2D2Cl2
d.e. 40 %
d.e. 17 %
d.e. 15 %
d.e. 10 %
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
H-2im H-8nap
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Chiral Concave NHC
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Can two methyl groups avoid rotation?
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NMR Experiments
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NMR Experiments
7.07.17.27.37.47.57.67.77.8 ppm
7.747.767.78 ppm 7.187.207.22 ppm 7.02 ppm
H-5napH-4ph
H-8nap
CDCl3
No diastereomeric excess!
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Increasing the Temperature
T = TCT < TC T > TC
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VT-NMR Experiments
No coalescence!
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Synthesis
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
n = 3,4
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Synthesis
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
n = 3,4
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Synthesis
n = 3,4
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
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Synthesis
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Outlook
• Application of the chiral concave NHC in asymmetric catalysis
• But first: chiral resolution!
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Acknowledgements
Lüning group
Prof. U. Lüning
Travel grant