Abstract
The process of discovery and development of a palladium(II)-catalyzed oxidative cross-coupling of N-acetyl and N-pivaloylindoles with simple aromatic compounds is described. Within this process our inspiration was primarily derived from the organometallic literature and in particular the recent emergence of new and novel mechanisms for C–H bond cleavage by Pd(II)-complexes. During these studies it was realized that high levels of regio-control for C–H bond cleavage at indole could be obtained and a subsequent investigation has led to the proposal of a C3,C2-palladium migration for the C2-arylation of N-pivaloylindole. The current state of the art in transition-metal catalyzed oxidative cross-coupling is also presented.
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Abbreviations
- [O]:
-
Oxidant
- Ac:
-
Acetyl
- acac:
-
Acetylacetonate
- AcO− :
-
Acetate
- BQ:
-
Benzoquinone
- CMD:
-
Concerted metalation–deprotonation
- DFT:
-
Density functional theory
- DMA:
-
N,N-dimethylacetamide
- DMF:
-
N,N-dimethylformamide
- DMSO:
-
Dimethylsulfoxide
- M:
-
Metal pre-activating group (BR2, SnR3, etc.)
- Me:
-
Methyl
- Ph:
-
Phenyl
- Piv:
-
Pivaloyl
- PivO− :
-
Pivalate
- Py:
-
Pyridine
- R:
-
Carbon-containing organic functional group
- t-Am:
-
tert-Amyl
- TBAB:
-
Tetrbutylammonium bromide
- t-Bu:
-
tert-Butyl
- TFA:
-
Trifluoroacetate
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Acknowledgements
I (DRS) will forever be indebted to Professor Keith Fagnou. His guidance, both scientifically and personally, was a constant source of inspiration during my graduate studies in his group. The entire Fagnou group is acknowledged for their support, in particular those that contributed to this chemistry: Elisia Villemure, Ivan Petrov, and Ho-Yan Sun. Sophie Rousseaux and Catherine Stuart are thanked for critical reading of this chapter at its various stages; and Prof. Gooβen is thanked for the opportunity to contribute to this anthology
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Stuart, D.R., Fagnou, K. (2012). The Discovery and Development of a Palladium(II)-Catalyzed Oxidative Cross-Coupling of Two Unactivated Arenes. In: Gooßen, L. (eds) Inventing Reactions. Topics in Organometallic Chemistry, vol 44. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3418_2012_52
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DOI: https://doi.org/10.1007/3418_2012_52
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