Organisch-Chemisches Institut,

Correnstraße 40, 48149 Münster SYNERGETISCHE EFFFEKTE IN DER CHEMIE

VON DER ADDITIVITÄT ZUR KOOPERATIVITÄT

“Click“-Triazoles in Organocatalysis:

Inert Structure or Active Function?

Stephan Beckendorf

14.08.2012

„Click“-Triazoles

in Organocatalysis 2

Very High Yielding

Wide in Scope

CuI catalyzed Azide-Alkyne Huisgen [3+2] Cycloaddition (CuAAC) Concept of „Click“-Chemistry

New properties should be

synthesized by reactions

that are…

Regio-/Stereospecific

…

„easy“ & efficient Synthesis

a) C. W. Tornoe, C. Christensen, M. Meldal, J. Org. Chem. 2002, 67, 3057; b) V. V.

Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem. Int. Ed. 2002,

41, 2596.

H. C. Kolb, M. G. Finn, K. B. Sharpless,

Angew. Chem. Int. Ed. 2001, 40, 2004.

Introduction

3 Introduction

„Click“-Triazoles

in Organocatalysis

„Click“-Triazoles in

Organocatalysis

„Click“-Triazoles in Lewis Acid Catalysis

Topic of this Presentation

What´s known in literature?

Defining our research goal

Research strategy

Results

Properties of „Click“-Triazoles in Lewis Acid Catalysis Properties of „Click“-

Triazoles in Organocatalysis

S. Beckendorf, O. García Mancheño, Synthesis 2012, 44,.2162 .

4

>>

Triazole as Innocent „Stealth“ Linkage

Triazoles as Active Function

Introduction

Publications ≥ 18

Publications ≥ 2

„Click“-Triazoles

in Organocatalysis

5

1,2,3-Triazole as Primary Catalyst Function?

Introduction

„Click“-Triazoles

in Organocatalysis

„Click“-1,2,3-Triazoles

In Organo Catalysis 6

Introduction

1,2,3-Triazoles as C–H∙∙∙Anion Hydrogenbonding Function

Review: Y. Hua, A. H. Flood, Chem. Soc. Rev. 2010, 39, 1262.

7 Introduction

Concept of Anion Accepetor Catalysis

Literature Example

Neutral H-bonding Anion Acceptors in Catalysis Reviews:a) Z. Zhang, P. R. Schreiner, Chem. Soc. Rev. 2009, 38, 1187. b)

S. Beckendorf, S. Asmus, O. García Mancheño, ChemCatChem 2012, 4, 926.

„Click“-Triazoles

in Organocatalysis

8 Goal

Can the Concept of Anion Acceptor Catalysis and the

1,2,3-Triazol C–H∙∙∙Anion Binding be Merged?

„Click“-Triazoles

in Organocatalysis

9 Research Strategy

Rational Design of „Click“-Triazole Anion Acceptor Catalysts

Fast and efficient syntheses of a small family of modular varied triazoles (DiTri).

Hypothesis: Catalytic activity and anion binding constant (K) should be correlated with each other.

Rational catalyst screening by measuring K via NMR-titration should be possible.

„Click“-Triazoles

in Organocatalysis

10

0.0

0.1

0.2

0.3

0.5

0.8

1.0

2.0

3.0

5.0

10

Ad

de

d e

qu

iva

len

ts o

f T

BA

Cl

H3 H2 H4 H5 H1

Screening

Measuring the Anion Binding Constant by NMR-Titration

„Click“-Triazoles

in Organocatalysis

11 Screening

Changing the Side Arms of the Ligand

Ratio of bounded chloride ions in a 5 mM acetone 1:1 solution of TBACl:Ligand

„Click“-Triazoles

in Organocatalysis

12 Theoretical Studies

„Click“-Triazoles

in Organocatalysis

Dr. Christian

Mück-

Lichtenfeld

De-Oxy-DiTri3∙Cl- De-Oxy-DiTri5∙Cl-

Kacetone(experimental): 458±56 M-1 Kacetone(experimental): 111±12 M-1

Binding Energy DE0K(theoretical): -9.1 kcal/mol

Optimized structures (B-LYP-D3(BJ)/def2-TZVP), COSMO solvation model e = 21.3, acetone), no thermodynamic correction

Binding Energy DE0K(theoretical): -7.9 kcal/mol

d- d- d+ d+

„Click“-1,2,3-Triazoles

In Organo Catalysis 13

Solvent Screening

Ratio of bounded chloride ions in a 5 mM 1:1 solution of TBACl:DiTri3 in different solvents

Screening

14 14 1st Application

Model Reaction

Temperature Screening

„Click“-Triazoles

in Organocatalysis

15 15 1st Application

Model Reaction

Solvent Screening

„Click“-Triazoles

in Organocatalysis

16 Substrate Scope

a) Reaction conditions: 1 (0.56 mmol, 2 equiv.), 2 (0.28 mmol, 1 equiv.) and DiTri3 (10 mol%)

in THF [0.2 M] at 45 °C for 72 h. Isolated yields of 3 are given. b) Formation of 3 not detected

by TLC in the non-catalyzed reaction. c) 3f was formed and isolated in <1% in the non

catalyzed reaction.

Substrate Scope

„Click“-Triazoles

in Organocatalysis

17 Proof of Concept

„Click“-Triazoles

in Organocatalysis

Catalysts Model Reaction

18 Proof of Concept

„Click“-Triazoles

in Organocatalysis

Model Reaction

Catalysts

19 Proof of Concept

„Click“-Triazoles

in Organocatalysis

Anion Selectivity

20 Conclusion

„Click“-Triazoles

in Organocatalysis

„Click“-Triazoles are useful

and flexible functionalities

Take Home Message

They can be used as

primary function in

C–H∙∙∙Anion Acceptor

Organocatalysts

21 Acknowledgement

Prof. Dr. Frank Glorius

&

Group Members

Analytical Departments

Audience

Dr. Olga Garcia Mancheño

&

Group Members

„Click“-Triazoles

in Organocatalysis

Dr. Christian Mück-Lichtenfeld

Financial Support