Intramolecular reactions basic principles

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. 

Over recent years a diverse range of methods has been developed for preparing selectively functionalized 3-sulfolenes. The use of such compounds as diene precursors for intermolecular and intramolecular Diels-Alder reactions has also been explored extensively. Thus, it is now possible to prepare and utilize substituted sulfolene intermediates in efficient strategies for the synthesis of complex organic molecules. There is, however, scope for more research into the basic principles underlying the preparation and reactions of substituted sulfolenes. 

Another important family of elimination reactions having cyclic transition states involves an intramolecular hydrogen transfer that accompanies elimination to form a new carbon—carbon double bond. These are thermally activated unimolecular reactions that normally do not involve acidic or basic catalysts. There is, however, a wide variation in the temperature at which elimination proceeds at a convenient rate. The cyclic transition state makes it mandatory that elimination occurs with syn stereochemistry. At least in principle, all such reactions can proceed by a concerted mechanism. Such reactions are often referred to as thermal syn eliminations. 

The most crucial step in all cases of the basic Gewald reaction and its improvements is the final ring-closure process, which is performed as an intramolecular nucleophilic attack of the sulfm anion to triple bond of the cyano group (Scheme 7). Target 2-aminothiophenes 7 in principle exists in equilibrium with the tautomeric forms - cyclic imines 11 formed during the cyclization. It was proved, that the parent aminothiophene occurs exclusively in the amino form [52-56]. 

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