Radical chemistry synthetic utility

The chemistry and utility of zinc-based Lewis acids are similar to those of their magnesium analogs. Their mild Lewis acidity promotes several synthetic reactions, such as Diels-Alder reactions, hetero Diels-Alder reactions,229 radical-mediated reactions,230 ene-type cyclization, and Simmons-Smith reactions. 

Electrophilic radical cyclizations of alkenyl aminium cation radicals have shown synthetic utility. Hofmann-Loffler-Freytag reactions do not compete with 5-exo cyclizations (75BSF1429). The homolytic cyclization of Af-chloroalkenylamines under acidic or Lewis acidic conditions has been studied primarily by Surzur and Stella, and the chemistry of these precursors for electrophilic aminyl radical generation has been reviewed [83AG(E)337]. Radical chain reactions can be initiated by heat, UV photol-... 

It should be evident that radicals play a very important role within the realm of organofluorine chemistry. Fluorine substituents impart unique reactivity characteristics to free radical intermediates, and knowledge of how to generate and utilize such species is very important for those synthetic chemists who wish to incorporate fluorinated alkyl groups into organic substrates. It has been attempted in this review to provide a strategic overview of all aspects of organo-fluorine radical chemistry, with the hope that readers with an interest in the field will able to get their basic questions answered as well as be stimulated to dig deeper into specific aspects of the subject via the detailed references which have been provided. 

New methods for the preparation of germanes and stannanes reported since 1995 are dealt with in Section n. In Section III, radical chain chemistry involving trialkyltin hydrides is examined. In particular, the synthetic utility of tributyltin hydride will be reviewed, as well as that of other stannanes. Recent advances in the area of asymmetric radical chemistry involving chiral non-racemic stannanes are also included. Section IV details a limited number of examples of non-radical stannane chemistry, while Section V covers recent advances in germane and plumbane chemistry. While we have restricted ourselves largely to the literature since the beginning of 1996, some salient features of earlier work are included when relevant to the discussion. 

There is no doubt that free-radical chemistry has benefited enormously through the invention of tin-based chain-carrying reagents " . Of these, tributyltin hydride and, to a lesser extent, triphenyltin hydride have been the reagents of choice. Their ready availability and favourable rate constants for attack of the corresponding tin-centred radicals at a variety of radical precursors , coupled with useful rate constants for hydrogen transfer to aUtyl and other radicals, provide for reagents superior to their silicon counterparts only tris(trimethylsilyl)silane rivals tributyltin hydride in its synthetic utility . 

In comparison with the rich chemistry of a radical anions the synthetic utility of a radical cations is quite restricted, because pure a donors are mostly limited to Si-Si, C-Si, C-Ge, and C-Sn functionalities (Scheme 18). Only strained carbocyclic compounds [119] have low ionization energies (/ ) that make them readily accessible (t(C-C) and cr(C-H) donors, but they are of limited synthetic use. In contrast, Me3M-MMe3 (M = Sn, Ge, Si lEs ranging from 8.0 to 8.3 eV) [5] and Me4M (M = Sn, Ge, Si lEs ranging from 8.9 to 9.8 eV) [5] are, in general, better donors... 

There is a considerable current interest in synthetic applications of radical cation chemistry. Alkene radical cations have been studied extensively, notable examples include the anti Markovnikov addition of nucleophiles [209], and the photo-NO-CAS reaction [210]. The synthetic utility of radical cation mediated chemistry, and... 

The current view of radical chemistry is slowly but surely establishing itself as a force to reckon with in the curriculum of undergraduate and postgraduate students. The earlier chapters gave only a brief taste of the spectrum of free radical chemistry available to the synthetic chemists to utilize and advance chemistry and understanding. Its envisaged that the chemistry described will only be limited by the creativity of the researcher. 

The chemistry of alkenyl radicals generated by reaction of SmU with alkenyl halides is much less well developed, and at this point in time appears to be of modest synthetic utility [28]. 

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... 

Nitroxides are persistent free radicals [1] which can often be isolated and handled as kinetically stable species. Nitroxides react rapidly with carbon free-radical intermediates [2] with well-characterized rate constants [3], and can thus be used as kinetic and mechanistic probes, as well as to trap carbon radicals in synthetic processes. They are easily oxidized or reduced, and thus have a rich redox chemistry that has been utilized for a variety of oxidations. As nitroxides have an unpaired electron, they are paramagnetic and thus ESR active, making them valuable as spin labels for biomolecules [4] and as spin traps for transient radicals [5]. In addition, nitroxides have been developed as organic ferromagnetic materials [6]. The synthesis of nitroxides has been reviewed in 1994 [7]. This review will focus on the synthetic applications of nitroxides. 

The control of anomeric stereochemistry continues to fuel the investigation into the synthetic utility of (x-oxygenated radical intermediates. Moreover, it has proven to be a valuable tool in organic synthesis, especially in the stereoselective synthesis of various substituted tetrahydropyrans, y>>n-l,3-dioxanes, and carbohydrate derivatives. The recent discovery of non-equilibrium radical reactions and conformation-induced self-regeneration of stereocenters should provide new opportunities in the ever-expanding field of a-oxygenated radical chemistry. 

The pioneering work on the calibration of intramolecular cy-clization of the 5-hexenyl radical by Ingold and co-workers provided the basis for the development of a large number of radical clocks." These are now used both for the calibration of rate constants for intermolecular radical reactions and as mechanistic probes to test for the intermediacy of radical intermediates in a variety of processes. Furthermore, the ready availability of bimolecular rate constants from competitive product studies using free radical clocks without the use of time-resolved experiments has greatly enhanced the synthetic utility of free radical chemistry. The same concept has recently been extended to radical ion chemistry. For example, rate constants for carbon—carbon bond cleavage reactions of a variety of radical cations and anions derived from substituted diarylethanes have been measured by direct time-resolved techniques. " ... 

Finally, a rearrangement of aryl esters and amides known as the photo-Fries rearrangement has occasionally found synthetic utility (Eq. 16.63). Although these reactions are superficially diverse, they all are initiated by a cleavage at the carbonyl, followed by conventional radical chemistry. 

Organic chemists apparently had little interest in radical chemistry in these early years. However, the enormous utility of the vinyl polymers and the critical need for synthetic rubber brought about by the second World War dramatically changed that. 

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