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
N-Heterocyclic Carbenes (NHC)
Different ring sizes…Different heteroatoms…
Bulky groups R are needed to avoid dimerization
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
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.
What can NHCs be used for?
As organocatalysts:
C. Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205.
What does “concave“ mean?
A Concave Catalyst
Concave system
Reactive centre
A Concave Catalyst
Concave system
Reactive centre
Solvent
Substrate
Functional group
Turn over number?
A Concave Catalyst
A Concave Catalyst
Concavebimacrocyclic
NHC
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.
* * * *
Chiral Concave NHC
Chiral Concave NHC
Problem: Interconversion by rotation at room temperature
Chiral resolution impossible!
NMR Experiments
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
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
Chiral Concave NHC
Can two methyl groups avoid rotation?
NMR Experiments
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!
Increasing the Temperature
T = TCT < TC T > TC
VT-NMR Experiments
No coalescence!
Synthesis
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
n = 3,4
Synthesis
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
n = 3,4
Synthesis
n = 3,4
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
Synthesis
Outlook
• Application of the chiral concave NHC in asymmetric catalysis
• But first: chiral resolution!
Acknowledgements
Lüning group
Prof. U. Lüning
Travel grant