tert-Butoxy-Radical-Promoted α-Arylation of Alkylamines with Aryl Halides
Ryota Ueno
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, 606-8502 Kyoto, Japan
Search for more papers by this authorYuko Ikeda
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, 669-1337 Hyogo, Japan
Search for more papers by this authorCorresponding Author
Eiji Shirakawa
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, 669-1337 Hyogo, Japan
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669-1337, Japan
E-mail: [email protected]
http://sci-tech.ksc.kwansei.ac.jp/en/
Search for more papers by this authorRyota Ueno
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, 606-8502 Kyoto, Japan
Search for more papers by this authorYuko Ikeda
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, 669-1337 Hyogo, Japan
Search for more papers by this authorCorresponding Author
Eiji Shirakawa
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, 669-1337 Hyogo, Japan
Department of Applied Chemistry for Environment, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo 669-1337, Japan
E-mail: [email protected]
http://sci-tech.ksc.kwansei.ac.jp/en/
Search for more papers by this authorGraphical Abstract
Just by adding a tert-butoxy radical precursor, alkylamines react with aryl halides to give α-arylalkylamines. The reaction proceeds through chemoselective homolytic aromatic substitution of the halogen atom (Br or Cl) by an α-aminoalkyl radical.
Abstract
In the presence of a tert-butoxy radical precursor, the reaction of alkylamines with aryl halides was found to give α-arylated alkylamines through homolytic aromatic substitution of the halogen atoms.
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References
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- 5For example, the reaction of bromobenzene (6.2 equiv.) with cyclohexane (5 equiv.) in the presence of tBuOOtBu (1 equiv.) gives a mixture of cyclohexylbenzene and bromo(cyclohexyl)benzenes (1:5). J. R. Shelton and C. W. Uzelmeier, J. Am. Chem. Soc., 1966, 88, 5222–5228.
- 6Several research groups have recently reported the α-arylation of heteroatom-containing aliphatic compounds with heteroaryl halides under photoredox catalysis. Although an HAS mechanism is considered to be operative, it is not clarified how the elimination of the halogen atom proceeds. The reaction requires a rather complicated photoredox system and the scope of aryl halides is limited to heteroaryl chlorides containing more than two heteroatoms on the aromatic ring: a) A. Singh, A. Arora, J. D. Weaver, Org. Lett. 2013, 15, 5390–5393;
- 7α-Arylation of secondary alkylamines is achieved e.g., through acylation of a secondary amine, deprotonation by butyllithium, transmetalation of the resulting α-(acylamino)alkyllithium with ZnCl2, the Negishi coupling with a heteroaryl halide, and deacylation: a) K. R. Campos, A. Klapars, J. H. Waldman, P. G. Dormer and C.-Y. Chen, J. Am. Chem. Soc., 2006, 128, 3538–3539;
- 8The reaction of 1a with a reduced amount (2 equiv.) of 4a resulted in a much lower yield (19 %, 5aa:5′aa = 84:16) with a low conversion (28 %) of 1a under the conditions of entry 1 of Table 1.
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- 10Aryl halides substituted with an electron-donating group such as 4-bromoanisole did not participate in the α-arylation at all.
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- 15The possibility that the halogen atom (X) undergoes elimination in a form of X– after single-electron reduction of cyclohexadienyl radical II by α-aminoalkyl radical I, giving α-arylation products 5 and iminium salts III, cannot be excluded. A similar mechanism has been proposed in the reduction of alkyl halides into alkanes by using α-aminoalkyl radicals: a) J. Lalevée, J. P. Fouassier, N. Blanchard, K. U. Ingold, Chem. Phys. Lett. 2011, 511, 156–158;
