“click“-triazoles in organocatalysis: inert structure or ... · „click“-triazoles in...
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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
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„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
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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 .
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4
>>
Triazole as Innocent „Stealth“ Linkage
Triazoles as Active Function
Introduction
Publications ≥ 18
Publications ≥ 2
„Click“-Triazoles
in Organocatalysis
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5
1,2,3-Triazole as Primary Catalyst Function?
Introduction
„Click“-Triazoles
in Organocatalysis
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„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.
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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
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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
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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
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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
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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
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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+
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„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
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14 14 1st Application
Model Reaction
Temperature Screening
„Click“-Triazoles
in Organocatalysis
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15 15 1st Application
Model Reaction
Solvent Screening
„Click“-Triazoles
in Organocatalysis
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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
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17 Proof of Concept
„Click“-Triazoles
in Organocatalysis
Catalysts Model Reaction
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18 Proof of Concept
„Click“-Triazoles
in Organocatalysis
Model Reaction
Catalysts
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19 Proof of Concept
„Click“-Triazoles
in Organocatalysis
Anion Selectivity
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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
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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