Transcript Chiral Concave N-Heterocyclic Carbenes

Chiral Concave
N-Heterocyclic Carbenes
Tim Reimers
Kiel, GER
3rd International Summer School
“Supramolecular Systems in Chemistry and Biology“
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:
Ad = Adamantyl
First crystalline carbene (1991)!
A. J. Arduengo III, R. L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361.
What can NHCs be used for?
As ligands in transition metal mediated reactions:
Olefin metathesis
Suzuki-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
Solvent
Concave system
Substrate
Reactive centre
Functional group
A Concave
Catalyst
Turn over number?
A Concave Catalyst
Concave
bimacrocyclic
NHC
Special Effect with a Concave NHC
*
*
*
*
52 %
n. o.
41 %
n. o.
X = (CH2)8
X = (CH2)10
3%
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
H-2im
H-8nap
CDCl3
d.e. 40 %
C2D2Cl4
d.e. 17 %
CD2Cl2
d.e. 15 %
C2D2Cl2
d.e. 10 %
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
Chiral Concave NHC
Can two methyl groups avoid rotation?
NMR Experiments
NMR Experiments
H-4ph
H-5nap
7.78
7.76
7.74
7.7
7.6
ppm
H-8nap
7.22
7.20
7.18
7.4
7.3
7.2
ppm
7.02
ppm
7.0
ppm
CDCl3
7.8
7.5
No diastereomeric excess!
7.1
Increasing the Temperature
T < TC
T = TC
T > TC
VT-NMR Experiments
No coalescence!
Synthesis
n = 3,4
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
Synthesis
n = 3,4
O. Winkelmann, D. Linder, J. Lacour, C. Näther, U. Lüning, Eur. J. Org. Chem. 2007, 3687-3607.
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
Prof. U. Lüning
Lüning group
Travel grant