Palladium-mediated cross-coupling chemistry

Palladium-mediated cross-coupling reactions in pteridine chemistry provide for variation at position 6 using halogenated pyrazines or pteridines as substrates (see Section 10.18.7.4). The 6-bromopyrazine 168 is a versatile intermediate leading to pteridine 169 both compounds have been shown to be substrates for palladium-mediated cross-coupling reactions <2000J(P1)89> (Scheme 32). 

The set of plans for the anticancer agent tamoxifen show a nice contrast between the original discovery route by Imperial Chemical Industries (ICI) [122,123], which uses classical chemistry versus modem routes that employ cross coupling chemistry mediated by palladium salt... 

The authors further explored the chemistry on solid support by decorating the obtained resin-bound 2-aminobenzothiazoles using different palladium-catalyzed cross-coupling reactions (Scheme 8.24). Thus, the reaction product of 3-bromoaniline was subjected to bromine-mediated cyclization in AcOH at rt for 16 h, furnishing a 1 1 mixture of 5- and... 

In summary, palladium-mediated reactions, especially cross-coupling reactions have found many applications in quinoline synthesis. It is noteworthy that due to the a and S activation for the C(2) and C(4) positions, even 2-chloro- and 4-chloro-quinolines are viable substrates for palladium-catalyzed reactions under standard conditions. With the advent of the palladium chemistry and more commercially available organometallic substrates, more palladium-mediated quinoline syntheses are to be added to the repertoire of quinoline chemistry. 

Hillier, A. C., Grasa, G. A., Viciu, M. S., Lee, H. M., Yang, C., Nolan, S. P. Catalytic cross-coupling reactions mediated by palladium/nucleophilic carbene systems. Journal of Organometallic Chemistry 2002, 653, 69-82. 

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