Radical reactions in synthesis

Most radicals are highly reactive, and there are few examples where one would produce a stable radical product in a reaction. Reference to a radical reaction in synthesis or in Nature, almost always concerns a sequence of elementary reactions that give a composite reaction. Multistep radical sequences are discussed in general terms in this section so that the elementary radical reactions presented later can be viewed in the context of real conversions. The sequences can be either radical chain reactions or radical nonchain reactions. Most synthetic apphcations involve radical chain reactions, and these comprise the bulk of organic synthetic sequences and commercial applications. Nonchain reaction sequences are largely involved in radical reactions in biology. Some synthetic radical conversions are nonchain processes, and some recent advances in commercial polymerization reactions involve nonchain sequences. 

The Utilization of free radical reactions in synthesis, particularly for the formation of carbon-carbon bonds, was given great impetus by initial studies... 

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. 

Although chain methods have been the foundation of the recent resurgence of radical reactions in synthesis, many of the earliest preparatively useful radical addition reactions were based on nonchain processes. Of late, such nonchain processes have regained importance. 

Chapter 24 Strategy XI Radical Reactions in Synthesis FGA and its Reverse. 

Chapter 22 Strategy X Use of Aliphatic Nitro Compounds in Synthesis. Chapter 24 Strategy XI Radical Reactions in Synthesis. FGA and its Reverse. Chapter 26 Strategy XII Reconnections. 

The first three chapters consider the fundamental topics of bonding theory, stereochemistry, and conformation. Chapter 4 discusses the techniques that are used to study and characterize reaction mechanisms. Chapter 9 focuses on aromaticity and the structural basis of aromatic stabilization. The remaining chapters consider basic reaction types, including substituent effects and stereochemistry. As compared to the earlier editions, there has been a modest degree of reorganization. The emergence of free-radical reactions in synthesis has led to the inclusion of certain aspects of free-radical chemistry in Part B. The revised chapter. Chapter 12, emphasizes the distinctive mechanistic and kinetic aspects of free-radical reactions. The synthetic applications will be considered in Part B. We have also split the topics of aromaticity and the reactions of aromatic compounds into two separate chapters. Chapters 9 and 10. This may facilitate use of Chapter 9, which deals with the nature of aromaticity, at an earlier stage if an instructor so desires. 

Pattenden, G. and Schulz, D.J. (1993) Cascade Radical Reactions in Synthesis. A New Radical Mediated Double Ring Expansion-Cyclization Process with Oxime Ethers, Tetrahedron Lett. 34, 6787-6790. 

Pattenden, G. and Robertson, G.M. (1986) Free radical reactions in synthesis. Total synthesis of isoamijiol. Tetrahedron Lett., 27,399-402. Mehta, G. and Krishnamurthy, N. (1987) An enantioselective approach to dolastane diterpenes. Total synthesis of marine natural products (+)-isoamijiol and (+)-dolasta-l(15),7,9-trien-14-ol. Tetrahedron Lett., 28, 5945-5948. 

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