Alkoxyl generation, reductive

Present in foodstuffs and various pharmacological and cosmetics products, organic peroxides are also generated during lipid peroxidation and prostaglandin biosynthesis. They readily undergo one-electron reduction and oxidation reactions, with the formation of alkoxyl and peroxyl radicals, respectively ... 

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-... 

Carbonate and carbamate derivatives, prepared from the reaction of alcohols and amines with phosgene and /V-hydroxy-2-thiopyridone, provide the corresponding alkoxyl radicals and aminyl radicals respectively, via radical decarboxylation [71-81]. For example, photolytic treatment of carbamate (57) derived from 4-pentenylamine generates the corresponding 4-pentenylaminyl radical, as shown in eq. 8.24. Under neutral conditions in the presence of tert-BuSH, a direct reduction product (A) of 4-pentenylaminyl radical is formed, while, in acidic conditions, cyclized product (C), pyrrolidine, via 5-exo-trig manner from 4-pentenylaminyl radical is formed. Under the latter conditions, the real reactive species is an electrophilic 4-pentenylaminium radical which rapidly cyclized via 5-exo-trig manner. 

Evidence for these pathways in vivo, and the initial involvement of HO radicals, has been presented [12]. An important feature of these protein-bound hydroperoxides is their sensitivity to reductive cleavage by transition metals, generating highly reactive alkoxyl radicals (Reaction (3.4)) [13]. 

Since alkyl- or alkoxyl-substituted silanes do not react readily with reducible functional groups, it soon became clear that the use of organotin oxides for in situ preparation of tin hydrides in the presence of PMHS was a possibility [32]. Several radical-based reductions have been performed to date using this approach [33]. The performance of in situ generated tributyltin hydride has been shown in many cases to be similar to the pre-prepared one, although in some cases it was found to be less effective. 

Fragmentation of Alkoxyl Radicals Generated under Reductive Conditions... 

The alkoxyl radical may be generated either directly by reduction of appropriate derivatives of alcohols or hemiacetals with tin hydrides [16-19] or iron(II) compounds [7], or indirectly by intramolecular addition of C- [lb, 20a] and yV-radicals... 

The results described herein demonstrate that the )9-fragmentation reaction of alkoxyl radicals generated under oxidative or reductive conditions is well suited for the synthesis of medium-sized and macro ketones and lactones. The system hyper-... 

Alternatively, the alkoxyl radical can attack an adjacent double bond to form an epoxide and a carbon-centered radical [36]. Subsequent addition of Oj generates an epoxyperoxyl radical that can form an epoxyhydroperoxide or undergo the reduction/ oxidation steps above to give an epoxyalcohol or epoxyketo fatty acid. Hydrolysis of the epoxide gives triol componnds. 

Tri-n-butyltin hydridejazodiisobutyronitrile Reductive generation of alkoxyl radicals Alcohols from nitric acid esters... 

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