Fischer, Carolin and König, Burkhard (2011) Palladium and copper mediated N-aryl bond formation reactions for the synthesis of biological active compounds. Beilstein Journal of Organic Chemistry (7), pp. 59-74.
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N-Arylated aliphatic and aromatic amines are important substituents in many biologically active compounds. In the last few years, transition-metal-mediated N-aryl bond formation has become a standard procedure for the introduction of amines into aromatic systems. While N-arylation of simple aromatic halides by simple amines works with many of the described methods in high yield, the reactions may require detailed optimization if applied to the synthesis of complex molecules with additional functional groups, such as natural products or drugs. We discuss and compare in this review the three main N-arylation methods in their application to the synthesis of biologically active compounds: Palladium-catalysed Buchwald–Hartwig-type reactions, copper-mediated Ullmann-type and Chan–Lam-type N-arylation reactions. The discussed examples show that palladium-catalysed reactions are favoured for large-scale applications and tolerate sterically demanding substituents on the coupling partners better than Chan–Lam reactions. Chan–Lam N-arylations are particularly mild and do not require additional ligands, which facilitates the work-up. However, reaction times can be very long. Ullmann- and Buchwald–Hartwig-type methods have been used in intramolecular reactions, giving access to complex ring structures. All three N-arylation methods have specific advantages and disadvantages that should be considered when selecting the reaction conditions for a desired C–N bond formation in the course of a total synthesis or drug synthesis.
|Date:||14 January 2011|
|Institutions:||Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König|
|Projects:||GRK 760, Graduiertenkolleg Medizinische Chemie|
|Keywords:||biologically active compounds; boronic acid; copper; N-arylation; palladium|
|Subjects:||500 Science > 540 Chemistry & allied sciences|
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Yes|
|Deposited On:||19 Jan 2011 10:50|
|Last Modified:||19 Jan 2011 10:50|