Introduction of Aromatic and Heteroaromatic Groups in the 2‐ and 8‐Positions of the Tröger’s Base Core by Suzuki, Stille and Negishi Cross‐Coupling Reactions – A Comparative Study

Abstract A comparative study on the bis(functionalization) of the Tröger’s base core by aromatic and heteroaromatic groups using palladium‐catalyzed cross‐coupling reactions is presented. Three different reactions, the Suzuki, Stille, and Negishi couplings, were investigated using Tröger’s base analogues equally substituted in the 2,8‐positions with (HO) 2 B, Bu 3 Sn and ZnCl groups, respectively, as the metallated component. Six aryl halides with different electronic and steric properties were employed as coupling partners. The presence of the bulky and electron‐rich phosphane P( t Bu) 3 as co‐catalyst was found to play an important role. In addition, the palladium source, [Pd(PPh 3 ) 4 ] or [Pd 2 (dba) 3 ], was also found to be an important factor for the yield of the reactions. The Suzuki coupling was found to be the best method in general, giving excellent yields for most aryl halides, whereas the Stille and Negishi couplings gave moderate to good yields. Finally, the crystal structures of the 4‐nitrophenyl‐ and the 2‐pyridyl‐appended analogues of Tröger’s base, 7d and 7f , are presented in the Supporting Information. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)