Radical reactions overview

The use of free-radical reactions in organic synthesis started with the reduction of functional groups. The purpose of this chapter is to give an overview of the relevance of silanes as efficient and effective sources for facile hydrogen atom transfer by radical chain processes. A number of reviews [1-7] have described some specific areas in detail. Reaction (4.1) represents the reduction of a functional group by silicon hydride which, in order to be a radical chain process, has to be associated with initiation, propagation and termination steps of the radical species. Scheme 4.1 illustrates the insertion of Reaction (4.1) in a radical chain process. 

The theme of this book is the formation, transformation, and application of ion-radicals in typical conditions of organic synthesis. Avoiding complex mathematics, this book presents an overview of organic ion-radical reactions and explains the principles of the ion-radical organic chemistry. Methods of determining ion-radical mechanisms and controlling ion-radical reactions are also... 

Abstract This review provides an overview of some of the more recent work directed to exploit radical-based chemistry for the modification of some of Natures most important biomolecules, such as amino acids, peptides, and carbohydrates. Radical reactions are particularly advantageous for carrying out a variety of structural modifications on biomolecules as the reaction conditions are typically compatible with a wide variety of functional groups and solvents. An array of effective synthetic transformations will he discussed including selective side chain and backbone modifications of amino acids and peptides, along with methods for the transformation of carbohydrate substituents, as well as fragmentation and cyclizations reactions for the preparation of either structurally modified carbohydrates or chiral building blocks. 

Saran M, Bors W. Radical reactions in vivo-an overview. Radiat. Environ. Biophys. 1990 29 249-262. 

The use of free radical chemistry at the anomeric center to produce carhon-carhon bonds, especially in an intramolecular fashion, remains a popular method for C-glycoside synthesis. A review entitled C-Glycosidation Technology with Free Radical Reactions appeared in early 1998, and the reader is referred to that somce [2] as well as to the more traditional ones for complete overviews on the subject. Again, the coverage here focuses on the most recent developments. 

Manganese(III)-mediated radical reactions have become a valuable method for the formation of carbon-carbon bonds over the past thirty years since the oxidative addition of acetic acid (1) to alkenes to give y-butyrolactones 6 (Scheme 1) was first reported by Heiba and Dessau [1] and Bush and Finkbeiner [2] in 1968. This method differs from most radical reactions in that it is carried out under oxidative, rather than reductive, conditions leading to more highly functionalized products from simple precursors. Mn(III)-based oxidative free-radical cyclizations have been extensively developed since they were first reported in 1984-1985 [3-5] and extended to tandem, triple and quadruple cyclizations. Since these additions and cyclizations have been exhaustively reviewed recently [6-11], this chapter will present an overview with an emphasis on the recent literature. 

In this chapter we have attempted to provide an overview of the application of computational chemistry to free-radical reactions of synthetic utility. We hope that the reader will be encouraged to add various modeling techniques to their chemical... 

Again the organometallic must be carefully chosen to be compatible with the deposition chemistries and temperatures used in the process. This cannot be overemphasized as more complex structures are deposited. The complexity of this task increases when all the reactants are organometallics because the carrier gas (hydrogen) also generally participates directly in the reaction to effectively convert initial radical reaction co-products into neutral, more stable ultimate species. An overview of precursors is provided by Jones [19]. 

III. Overview and Comments on Free Radical Reactions in Reactive Plasmas. 233... 

In this section, therefore, an overview of and comments on free radical reactions are given from a physicochemical viewpoint. 

The present overview starts with early historical developments. The Pd-catalyzed reaction of organotin compounds was first published by Eabom s group in 1976 (Scheme It was initially considered as a variation of the Kharasch-type reaction, namely, radical reaction. 

For an early overview on the use of stoichiometric amounts of cobalt complexes, see Pattenden, G. (1988) Cobalt-mediated radical reactions inorganic synthesis. Chem. Soc. Rev., 17, 361-82. 

Most radical reactions can be conducted under rruld conditions. In contrast to ionic reactions and many transition metal-mediated processes, most of the functional groups are tolerated under radical conditions. Moreover, radical reactions can be performed in various solvents even water is tolerated as a reaction medium. These facts, among others, make radical processes highly useful for arylations. Radical arylations can be performed using SsNl-type reactions, by homolytic aromatic substitutions, and by reactions of aryl radicals with various radical acceptors. In this chapter we first focus on SR Ttype reactions [1], and later concentrate on homolytic aromatic substitutions. Unfortunately, due to limitations of space, we cannot provide a comprehensive overview on this topic hence, for further information the reader is referred to some excellent reviews on this issue [2]. 

Most organic reactions result from the union of an electron-rich nucleophile (Nu ) with an electron-poor electrophile (E+). (Exceptions to this generalization include radical reactions, pericyclic reactions, and reactions mediated by organometaUic species.) In order to properly plan for an organic synthesis, one must be familiar with commonly used electrophiles and nucleophiles. Presented in this section is an overview of such species, all of which are either commercially available or readily prepared. These nucleophiles and electrophiles will be employed throughout this book as their reactions and uses in synthesis are presented in detail in subsequent chapters. 

An overview of die free radicals and reactions thereof is presented. Free radicals are atoms or groups having an unpaired electron and hence are paramagnetic. Electron paramagnetic resonance spectroscopy (EPR) and trapping methods are used to analyze radicals. In lipids, radical reactions lead to autoxidation and hence flavor reversion. Reactive oxygen species are key components involved in such reactions. Finally, descriptions for phenolic, sequesterant and enzymatic antioxidants and their mode of action are provided. 

Rush JD, Koppenol WH (1986) Oxidizing intermediates in the reaction of ferrous EDTA with hydrogen peroxide. Reactions with organic molecules and fer-rocytochrome c. J Biol Chem 261 6730-6733 Saran M, Bors W (1990) Radical reactions in vivo - an overview. Radiat Environ Biophys 29 249-262... 

The driving force for a HAT reaction, AG°xh/y =- 7 ln. Kxh/y. is best determined by direct equilibrium measurements in the solvent of interest. However, this is typically limited to reactions where IAG°xh/yI is small, less than about 5 kcal mol . Also, this is only possible for reactions in which all of the species are fairly stable, which is unusual for organic radical reactions. The AG° for a HAT reaction is typically more easily derived as the difference in bond dissociation free energies (BDFEs) of X-H and Y-H in the solvent of interest. We have recently reviewed BDFEs of common organic and biochemical species and how they are obtained, so only an overview is given here. 

We begin with a discussion of hydrogenation, focusing on the details of catalytic activation. Then we turn to the largest class of addition processes, those in which electrophiles such as protons, halogens, and metal ions are added to the alkene. Other additions that will contribute further to our synthetic repertoire include hydroboration, several oxidations (which can lead to complete mpture of the double bond if desired), and radical reactions. Each of these transformations takes us in a different direction the Reaction Summary Road Map at the end of the chapter provides an overview of the interconversions leading to and from this versatile compound class. 

The aim of this chapter is to provide an overview of the utility of radical synthetic methods for constructing valuable intermediates in target-oriented synthesis of natural products. The chapter is organized according to the methods used in carbon-carbon, bond-forming radical reactions. Representative examples of the successful implementation of radical-promoted stereoselective carbon-carbon formation published since 1991 are presented, most of which, as will become apparent, involve substrate-controlled diaster-eoselective radical cyclizations. ... 

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