Microwave-assisted Transition Metal-catalyzed Coupling Reactions

Microwave-Assisted Transition Metal Catalyzed Coupling Reactions 

Halogen-substituted 2-pyridones are key intermediates for further metal-catalyzed coupling reactions and the halogenation of these scaffolds has already been described in previous sections. In the following section, a variety of C - C and C - N cross-coupling reactions under microwave-assisted conditions are described with some illustrative examples. 

Microwave-assisted Transition Metal-catalyzed Coupling Reactions 

Kristofer Olofsson, Peter Nilsson, and Mats Larhed 15.1 

In recent decades much effort has been devoted to extending the scope of palladium, copper, and nickel-catalyzed reactions proceeding via aryl or vinyl metal intermediates [12]. These coupling reactions have enabled the formation of many kinds of carbon-carbon and carbon-heteroatom connections that were previously very difficult to realize. Metal-mediated transformations have proven especially valuable for introduction of substituents to aromatic core structures. They allow the presence of a wide variety of functional groups and perform equally well in both inter and intramolecular applications. Furthermore, in homogeneous catalysis, 

Microwaves in Organic Synthesis Second edition. Edited by A. Loupy Copyright 2006 WILEY-VCH Veriag GmbH Co. KGaA, Weinheim ISBN 3-527-31452-0 

It has been our ambition in writing this chapter not to give a complete overview of microwave-assisted metal-catalyzed transformations of aryl and vinyl halides (or pseudo halides) - which is indeed impossible within the scope of this edition - but rather to focus selectively both on medicinal chemistry and papers with a recent publication date. Especially in sections in which the number of publications is large we have opted for a deeper discussion of selected topics and a few topics covered in the last edition have been removed. 

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I J5 Microwave-assisted Transition Metal-catalyzed Coupling Reactions... 

Olofsson, K., Nilsson, P. and Larhed, M. (2006) Microwave-assisted transition metal-catalyzed coupling reactions, in Microwaves in Organic Synthesis, 2nd edn (ed. A. Loupy), Wdey-VCH Verlag GmbH, pp. 685-725. 

AT-acetyltryptamines could be obtained via microwave-assisted transition-metal-catalyzed reactions on resin bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide. While acceptable reaction conditions for the application of microwave irradiation have been identified for Stille heteroaryla-tion reactions, the related Suzuki protocol on the same substrate gave poor results, since at a constant power of 60 W, no full conversion (50-60%) of resin-bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide could be obtained even when two consecutive cross-coupling reaction cycles (involving complete removal of reagents and by-products by washing off the resin) were used (Scheme 36). Also under conventional heating at 110 °C, and otherwise identical conditions, the Suzuki reactions proved to be difficult since two cross-coupling reaction cycles of 24 h had to be used to achieve full conversion. 

Compared to the previously described transition metal-catalyzed transformations in this chapter, microwave-assisted Stille reactions [74] involving organotin reagents as coupling partners are comparatively rare. A few examples describing both inter- and intramolecular Stille reactions in heterocyclic systems are summarized in Scheme 6.38 [47, 75-77]. Additional examples involving fluorous Stille reactions are described in Section 7.3. 

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