Radical reactions sequential

Synthetic strategies based on multistep radical reactions have steadily grown in popularity with time. The knowledge of radical reactivity has increased to such a level as to aid in making the necessary predictions for performing sequential transformations.Silanes, and in particular (TMSlsSiH, as mediators have contributed substantially in this area, with interesting results in terms of reactivity and stereoselectivity. ... 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

Scheme 6.7 Sequential radical reactions including 5-endo-trig cyclization of silyl radical...

The majority of sequential radical reactions using silanes as mediators for the C—C bond formation deal with (TMS)3SiH. Nevertheless, as we shall see there are some interesting applications using other silanes, too. 

This chapter begins with an introduction to the basic principles that are required to apply radical reactions in synthesis, with references to more detailed treatments. After a discussion of the effect of substituents on the rates of radical addition reactions, a new method to notate radical reactions in retrosynthetic analysis will be introduced. A summary of synthetically useful radical addition reactions will then follow. Emphasis will be placed on how the selection of an available method, either chain or non-chain, may affect the outcome of an addition reaction. The addition reactions of carbon radicals to multiple bonds and aromatic rings will be the major focus of the presentation, with a shorter section on the addition reactions of heteroatom-centered radicals. Intramolecular addition reactions, that is radical cyclizations, will be covered in the following chapter with a similar organizational pattern. This second chapter will also cover the use of sequential radical reactions. Reactions of diradicals (and related reactive intermediates) will not be discussed in either chapter. Photochemical [2 + 2] cycloadditions are covered in Volume 5, Chapter 3.1 and diyl cycloadditions are covered in Volume 5, Chapter 3.1. Related functional group transformations of radicals (that do not involve ir-bond additions) are treated in Volume 8, Chapter 4.2. 

The purpose of this chapter is to provide an introduction to the scope and limitations of radical cyclization reactions. Emphasis will be placed on the reactivity profile of radicals with respect to chemo-, regio-and stereo-selectivity. Because most sequential radical reactions include at least one cyclization, they are also presented in this chapter. The organization of this chapter is similar to the previous chapter on radical additions. However, the basic principles of radical reactions, selectivity requirements, methods to conduct radical reactions (including experimental techniques), and mechanisms are extensively discussed in the previous chapter, and these aspects will be reiterated rather sparingly. A reader who is not familiar with the principles of radical reactions as applied to synthesis should read the addition chapter (Chapter 4.1, this volume) first. 

The types of reactions that are sequenced and the order in which they occur often dictate the choice of an appropriate method. Thus, sequential radical reactions are classified by transformation, and they are presented below in roughly increasing order of difficulty. With careful substrate design and selection of an appropriate method and reaction conditions, a diverse collection of tandem radical reactions has been executed. Yet the known reactions only begin to show the potential of such radical sequences for the rapid assemblage of complex molecules. 

Deprotonation is essential in some cation radical reactions the corresponding examples will be described in Chapter 6. Scheme 1-43 depicts a photoreaction between phenan-threne and triethylamine. This reaction includes photoinduced sequential electron-transfer, proton-transfer, and radical-recombination processes (Lawson et al. 1999). 

Transformation of many compounds appears to be direct, without detectable chlorinated intermediates. In some cases, direct transformation occurs in parallel with other reactions, such as the formation of radicals or sequential dehalogenation. Some alkanes (1,1,2,2-TCA) appears to be dehalogenated sequentially, while others (DBCP) first undergo elimination to form an alkene, followed by complete dehalogenation and hydrogenation. Hydrogenation of PAHs is reversible products form equilibrium ratios. 

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