Free-radical-mediated Multicomponent Coupling Reactions

Free-radical-mediated Multicomponent Coupling Reactions 

Radicals add to unsaturated bonds to form new radicals, which then undergo addition to other unsaturated bonds to generate further radicals. This reaction sequence, when it occurs iteratively, ultimately leads to the production of polymers. Yet the typical radical polymerization sequence also features the essence of radical-induced multicomponent assembling reactions, assuming, of course, that the individual steps occur in a controlled manner with respect to the sequence and the number of components. The key question then becomes how does one control radical addition reactions such that they can be useful multicomponent reactions Among the possibilities are kinetics, radical polar effects, quenching of the radicals by a one-electron transfer and an efficient radical chain system based on the judicious choice of a radical mediator. This chapter presents a variety of different answers to the question. Each example supports the view that a multicomponent coupling reaction is preferable to uncontrolled radical polymerization reactions, which can decrease the overall efficiency of the process. 

Multicomponent Reactions. Edited by Jieping Zhu, Hugues Bienayme Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30806-7 

respectively [5]. These values are three orders of magnitude larger than that for addition to terminal alkenes such as 1-hexene. For this reason, electron-deficient alkenes are frequently employed for multicomponent reactions. However, as the resulting radicals have an electron-withdrawing group they are now electrophilic, and are likely to add to electron-rich alkenes with reasonable rate constants. 

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Free-radical-mediated Multicomponent Coupling Reactions... 

This chapter contains a survey of free-radical-mediated multicomponent reactions (MCRs), which permit the coupling of three or more components. Even though they are not technically classified as MCRs, remarkable intramolecular radical cascade processes have been developed. Some examples, such as those shown in Scheme 6.3, use an isonitrile or acrylonitrile as the intermolecular component for each reaction [6]. These examples demonstrate the tremendous power of the combination of inter- and intramolecular radical cascade processes in organic synthesis. Readers are advised to be aware of remarkable intramolecular aspects of modem radical chemistry through excellent review articles published elsewhere [1, 7]. It should also be noted that there has also been remarkable progress in the area of living radical polymerizations, but this will not be covered here. 

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