Amination

Chemfiles Volume 7 Article 5

In combination with common Pd precursors, Q-Phos has proven to be an excellent ligand for amination of aryl chlorides and aryl bromides of varying electronic character with both primary and secondary amines.1 Typically, the amination reactions reach completion in less than 24 hours at temperatures of <=100 °C, and in certain cases, the reaction proceeds rapidly at room temperature. In most instances, only small amounts of hydrodehalogenated byproducts are observed. The reaction protocol is straightforward and general, relying on either Pd(dba)2 or Pd(OAc)2 as a palladium source, and a base/solvent system of either NaOt-Bu/toluene or K3PO4/DME. As illustrated in Table 1, diarylamines rapidly couple with aryl bromides at room temperature (entry 1). Less expensive aryl chlorides also couple in high yield, although higher temperatures are required (entry 2). Similarly, alkylarylamines, dialkylamines, and anilines are viable nucleophiles for the coupling reaction (entries 3–7). In the case of primary aliphatic and benzylic amines, the amination was remarkably selective for the monoarylated product (entries 8 and 9). Finally, for some substrates, it is possible to conduct the amination at low catalyst loadings (e.g., entry 10).


Table 1.

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References

  1. Kataoka, N. et al. J. Org. Chem. 2002, 67, 5553.

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