Carbon-carbon coupling reaction (Msc chemistry)

1. A Seminar Presentation
On
Strategies and Mechanisms of C-C coupling reactions
By
Richard Kayode Adeleke
Matric No: 20/57MCH/00009
Supervised by: Prof. O. O. James
12th July, 2023
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2. Outlines
• Introduction
• Carbon: Electronic configuration and bonding
• Insights from C-C bond cleavages
• Strategies of C-C bond formations
• Examples of Aliphatic C-C bond formations
• Examples of Aromatic C-C bond formations
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3. Introduction
Synthetic organic chemistry is the art & science of constructing
new and larger carbon-based organic molecules from smaller
building blocks.
These new organic molecules are formed through chemical
transformations that are often performed in sequence and in a
specific order.
(Nicolaou et al., 2005)
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4. Carbon
Electronic configuration of carbon
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(Armano & Agnello, 2019)

5. Hybridization of carbon
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The sp3 bond
The sp2 bond
The sp bond
(Armano & Agnello, 2019)

6. Bonding
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The sigma (σ) bond
The pi (π) Bond
Jemmis (2006)

7. Insights from C-C bond cleavages
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Zweife and Nantz (2007)
Homolytic cleavage
Heterolytic cleavage
Nucleophile & Electrophile
Substrate & Reagent
Radicals
Substrate & Reagent
Use hypothetical reactions like in heterolytic

8. 8
Strategies of C-C bond formation
Homolytic C-C coupling
Heterolytic C-C coupling
Both or at least either the substrate or the reagent is a radical
The C-C coupling will be initiated by radical generation
Either of the substrate and the reagent must be nucleophile or electrophile
The C-C coupling will be depend on careful matching of the coupling species
Nucleophile substrate vs Electrophile reagent
or
Electrophile substrate vs Nucleophile reagent

9. Examples of Aliphatic C-C bond formations
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Homolytic C-C coupling
• Radical addition
Smith et al., (2007)
• Radical Cyclization
the reagent, radical initiator generate the radical substrate
the radical substrate is added to more substrate

10. 10
Heterolytic C-C coupling
Electrophile substrate vs Nucleophile reagent
• Acid catalysed aldol condensation
(Kingsbury & Schelble 2001)
• The allyl silanes reaction
(Wade 2005)
nucleophile enol attacks the electrophile (substrate)
electrophile (substrate) converted into nucleophile Enol
nucleophile
(reagent)
Electrophile
(substrate)
Lewis acid activation enhances electrophilicity of the substrate
The nucleophile reagent attacks the enhanced electrophilic substrate

11. 11
Electrophile substrate vs Nucleophile reagent, cont’d
• The reaction od acetylides with Carbonyls
• The alkylation of acetylide ions
(John 2010)
electrophile (substrate)
nucleophile (reagent)
nucleophile (reagent)
electrophile (substrate)

12. Heterolytic C-C coupling
Nucleophile substrate vs Electrophile reagent

13. 13
Examples of Aromatic C-C bond formations
Homolytic C-C coupling
• Ullmann coupling reation
• Gomberg-Bachmann reaction
(Yin & Liebscher 2017)
(Gomberg and Bachmann 1928)
Radical generation via
single electron transfer
Radical C-C coupling
Radical generation via hydroxide ion catalyzed
liberation of N2 from diazonium cation
Radical C-C coupling

14. 14
Aromatic Heterolytic C-C coupling
Nucleophile substrate vs Electrophile reagent
Friedel–Crafts acylation
Friedel–Crafts alkylation
(Kingsbury & Schelble, 2001)
generation of the electrophile specie
Nucleophile (substrate)
Electrophile (reagent)
generation of the electrophile specie
Nucleophile (substrate)
Electrophile (reagent)

15. 15
Heterolytic C-C coupling
Electrophile substrate vs Nucleophile reagent
The organocuprates reaction
The Suzuki Reaction
(Kingsbury & Schelble, 2001)
Electrophile (substrate)
Electrophile (substrate)
Nucleophile (reagent)
Nucleophile (reagent)

16. Conclusion
- Bond fission and formation is an integral elementary steps in organic
synthesis.
- C-C coupling reactions can occur via radical coupling or nucleophile-
electrophile coupling.
- Radical C-C coupling has to be initiated by radical carbon generation step
- Many C-C coupling reactions can rationalized in terms of cross matching of
nucleophile (substrate) vs electrophile (reagent) and vice-versa.
- C-C coupling reaction is critical to design of synthesis schemes of many
useful organic compounds such as drugs, dyes, monomers, etc
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17. Reference
• Yin; Liebscher, Jürgen (2007). "Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts".
Chemical Reviews. 107 (1): 133–173. doi:10.1021/cr0505674
• Wade, L. G. (2005). Organic Chemistry (6th ed.). Upper Saddle River, New Jersey: Prentice Hall. pp. 1056–66. ISBN 978-0-
13-236731-8.
• Zweifel, G. S.; Nantz, M. H. (2007). Modern Organic Synthesis: An Introduction. W.H. Freeman and Co. ISBN 978-0-7167-
7266-8
• Smith, Michael B.; March, Jerry (2007), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure (6th ed.),
New York: Wiley-Interscience, ISBN 978-0-471-72091-1
• Gomberg, M.; Bachmann, W. E. J. Am. Chem. Soc. 1924, 46, 2339.
• King, A. O.; Yasuda, N. (2004). "Palladium-Catalyzed Cross-Coupling Reactions in the Synthesis of Pharmaceuticals".
Organometallics in Process Chemistry. Topics in Organometallic Chemistry. Vol. 6. Heidelberg: Springer. pp. 205–245.
doi:10.1007/b94551. ISBN 978-3-540-01603-8
• Jemmis, Eluvathingal D. ; Pathak, Biswarup; King, R. Bruceb; Schaefer III, Henry F. (2006). "Bond length and bond
multiplicity: σ-bond prevents short π-bonds". Chemical Communications (20): 2164–2166. doi:10.1039/b60211
• Cheng J, Zhang G, Du J, Tang L, Xu J, Li J (2011) J Mater Chem 21:3485–3494
• Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. (2005). Palladium-Catalyzed Cross-Coupling Reactions in Total Synthesis. Angew.
Chemie Int. Ed., 44(29), 4442-4489
• Kingsbury, C., & Schelble, S. (2001). Organic chemistry. In Journal of Chemical Education (Vol. 78, Issue 9). Pearson
Education.
• Armano, A., & Agnello, S. (n.d.). Properties of Single-Layer Graphene. 1–37. https://doi.org/10.3390/c5040067
• John McMurry 2010; Book or Source : Organic Chemistry Page and Part : 9th.
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18. THANK YOU
FOR
LISTENING
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