Radical cyclizations fragmentation method

The selection of the thirty procedures clearly reflects the current interest of synthetic organic chemistry. Thus seven of them illustrate uses of T1(I), T1 (III), Cu(I), and Li(I), and three examples elaborate on the process now termed phase-transfer catalysis. In addition, newly developed methods involving fragmentation, sulfide contraction, and synthetically useful free radical cyclization arc covered in five procedures. Inclusion of preparations and uses of five theoretically interesting compounds demonstrates the rapid expansion of this particular area in recent years and will render these compounds more readily and consistently available. 

Relatively few kinetic data are available for the carbon-carbon bond forming reactions of alkene radical cations. Nevertheless, rate constants for the cyclization illustrated in Scheme 9, with generation of the alkene radical cation by the fragmentation method, have been measured. These cyclization rate constants are significantly faster than those of the corresponding neutral radicals [89]. 

Conducting radical cyclizations by fragmentation reactions offers a powerful alternative to the tin hydride method. Instead of. obtaining reduced products, one obtains products of substitution an alkene is regenerated in the fragmentation step. 

Phenyl o-radicals generated by reduction of aryl halides can also interact with an intramolecular alkene bond. Ihe method has been developed for the formation of dihydroindoles by reductive cyclization of N-allyl-2-chloroacetanilides. The results indicate the importance of a time interval between electron addition to give a radical-anion and the fragmentation of this species to give the active a-radical, The time interval allows the radical-anion to diffuse away from the electrode surface so that when the a-radical is foimed, it has time to cyclize before it can be reduced at the surface. 

Alkoxyl radicals can be generated by a variety of methods including peroxide reduction, nitrite ester photolysis, hypohalite thermolysis, and fragmentation of epoxyalkyl radicals (for additional examples of alkoxyl radical generation, see Section 4.2.S.2). Hypohalites are excellent halogen atom donors to carbon-centered radicals, and a recent example of this type of cyclization from the work of Kraus is illustrated in Scheme 43.182 Oxidation of the hemiketal (57) presumably forms an intermediate hypoiodite, which spontaneously cyclizes to (58) by an atom transfer mechanism. Unfortunately, the direct application of the Barton method for the generation of alkoxyl radicals fails because the intermediate pyridine-thione carbonates are sensitive to hydrolytic reactions. However, in a very important recent development, Beckwith and Hay have shown that alkoxyl radicals are formed from N-alkoxypyridinethiones.183 Al-... 

Fig. 1.42. Cyclization of a 5-hexenyl radical intermediate from a Barton-McCombie defunctionalization as a method for cyclopentane annulation (cyclizing defunctionalization, in terms of Figure 1.2 this means a "substitution including a fragmentation and an addition ).

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. 

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