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Synthesis 2022; 54(02): 334-340
DOI: 10.1055/s-0037-1610784
DOI: 10.1055/s-0037-1610784
feature
Late-Stage C–H Arylation of Azepinoindole via Pd/Cu Catalysis: A Step Efficient and Convergent Synthesis of Rucaparib
The research leading to these results has received funding from the NMBP-01-2016 Program of the European Union’s Horizon 2020 Framework Program H2020/2014-2020/ under grant agreement no (720996). DDV is grateful to KU Leuven for support in the frame of the CASAS Metusalem project and to Research Foundation Flanders (FWO) for project funding (G0781118 N, G0D0518 N). Mass spectrometry was made possible with the support of the Hercules Foundation of the Flemish Government (grant 20100225–7).
Abstract
The C–H arylation of indoles holds the promise to shorten synthetic routes in the production of pharmaceuticals. However, late-stage C–H activation reactions often rely on the presence of protecting groups or stoichiometric metal additives. The regiospecific C–H arylation of a highly functionalized azepino[5,3,4-cd]indole scaffold lacking directing groups via Pd(II) and Cu(II) co-catalysis is reported. The direct C–H coupling was demonstrated in the convergent synthesis of rucaparib, an FDA approved anticancer drug.
Key words
C–H activation - indole - arylation - homogeneous catalysis - palladium - copper - organic synthesis - pharmaceuticalsPublication History
Received: 06 July 2021
Accepted after revision: 06 August 2021
Article published online:
17 September 2021
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