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