Introduction: Free-Radical Reactions in Carbohydrate Chemistry

I. The Emergence of Free-Radical Reactions

The success of free-radical reactions in chemical synthesis is one of the remark­able developments in chemistry during the past several decades. Investigation and application of these reactions continues ­unabated at present and shows no sign of decreasing in the future. To appre­ciate the rapid rise of free-radical reactions to their position of prominence in the syn­thesis of organic compounds, it is only necessary to compare the wealth of information in existence today with the modest amount of material that was available prior to the 1970s. This comparison is easily done by con­sult­ing some of the many books and review articles describing the develop­ment of var­ious aspects of free-radical chemistry during the past several dec­ades.^1-102 (Free-radical polymer formation has a different history. Considerable information on this topic existed prior to the 1970s.)

Once extensive investigation began, synthetic, free-radical chemistry matured so rapidly that by 1993 it was possible to state with confidence ­that “radical reac­tions, even with highly complex and heavily sub­sti­tuted sub­strates, can be con­ducted in a highly selective and efficient man­ner."²³ Assess­ments such as this, which continue to be reinforced as additional discoveries are made, leave little doubt about the impor­tance of radical reac­tions; yet, chemists saw these processes much differently ­earlier in the 1900s. In reflecting on these earlier times, the pioneering, free-radical chemist C. Walling noted that most chemists considered radi­cal reac­tions to be "messy, unpredictable, unpromising and essentially mys­ter­ious".⁷

What caused such a dramatic change in attitude toward radical reac­tions? Undoubtedly there were a number of reasons, but several are par­tic­u­larly note­worthy. One of these is the discovery of radical-based reac­tions for such syn­thetically important transformations as extending carbon-atom chains, creating new ring systems, and altering substitution patterns. Another decis­ive factor is the sophistication, based largely on careful mea­sure­ment of rate constants, that researchers developed in adjusting reaction conditions to favor specific pathways. Also influ­ential is the information dis­cov­ered about ways to conduct radical reactions under mild con­di­tions. All of these factors par­tic­i­pated in changing attitudes toward free-radical reac­tions to the point that these reactions became recognized as powerful syn­the­tic tools and con­sidered to be valuable compliments to their ionic coun­ter­parts.¹⁰³

II. The Role of Free-Radical Reactions in Carbohydrate Synthesis

The characteristics of free-radical reactions are well suited for trans­for­mation of multifunctional compounds such as carbo­hydrates. The presence of many functional groups in a compound can open a variety of easily acti­vated reac­tion pathways; consequently, any mild reac­tion that accomplishes a desired structural change in the face of many possible changes is greatly prized. The high levels of selectivity and mild conditions char­ac­ter­istic of many radical reactions make these processes particularly attractive for carbo­hydrate synthesis.

III. Chain Reaction: A Natural Pathway for Free-Radicals

Free radicals in solution tend to combine with each other at rates that are close to the highest possible, that is, rates approaching those at which reactants diffuse through a solution.¹⁰⁴ Rapid radical combination dictates that to observe other radical reactions, a low con­cen­tration of radical intermediates must be main­tained. The problem of avoiding radical combination ­and, at the same time, promoting other radical reac­tions finds a natural solution in the use of chain reactions. Efficient chain reactions are pro­cesses in which each of a small number of radicals starts a sequence of reactions that is repeated many times before a reaction such as radical combination terminates the chain. The match between the need to maintain low radical concentration ­­and the benefit that low con­cen­tration brings to chain reactions naturally leads to many of the most useful, free-radical reactions being chain processes. It is reason­able (per­haps man­da­tory), therefore, to begin describ­ing ­free-radical chemistry with a detailed discussion of chain reactions. Such a dis­cus­sion is the focus of the next chapter.