Radical coupling with hydroperoxides

As indicated in Scheme VII/32, cyclononanone (VII/165) is transformed into hydroperoxide hemiacetal, VII/167, which is isolated as a mixture of stereoisomers. The addition of Fe(II)S04 to a solution of VII/167 in methanol saturated with Cu(OAc)2 gave ( )-recifeiolide (VII/171) in quantitative yield. No isomeric olefins were detected. In the first step of the proposed mechanism, an electron from Fe2+ is transferred to the peroxide to form the oxy radical VII/168. The central C,C-bond is weakened by antiperiplanar overlap with the lone pair on the ether oxygen. Cleavage of this bond leads to the secondary carbon radical VII/169, which yields, by an oxidative coupling with Cu(OAc)2, the alkyl copper intermediate VII/170. If we assume that the alkyl copper intermediate, VII/170, exists (a) as a (Z)-ester, stabilized by n (ether O) —> <7 (C=0) overlap (anomeric effect), and (b) is internally coordinated by the ester to form a pseudo-six-membered ring, then only one of the four -hydrogens is available for a syn-//-elimination. [111]. This reaction principle has been used in other macrolide syntheses, too [112] [113]. 

The methoxycarbonylmethyl radical I is obtained by Kolbe electrolysis from methyl-malonate [Eq. (4, path a)], and in homogeneous solution by reductive fragmentation of the hydroperoxide of dimethyl acetone dicarboxylate [Eq. (4, path b)]. Radical I forms with styrene the adduct II, which reacts by disproportionation to III and IV, by coupling with I to V and by dimerization to VI. The yields and product ratios for the electrolysis and the reductive fragmentation correspond surprisingly well, and no extensive polymerization was found for the homogeneous reaction. 

Indirect reduction of / -butyl hydroperoxide by aromatic radical anions in DMF gives /-butoxy radicals which abstract hydrogen from DMF. The resulting A,A-dimethy-laminocarbonyl radical may couple with the mediator [216]. 

The mechanism of the key fragmentation involves initial transfer of an electron to hydroperoxide 30 (Eq. 1.2) from Fe, forming intermediate 30a, which then cleaves homolytically to the carbon radical 30b. Oxidative coupling with Cu(OAc)2 then forms 30c in which the ester moiety is in the stable Z-configuration, stabilized by internal coordination via a psuedo six-membered ring. From this intermediate, only one hydrogen atom (Ha) is available for syn elimination and, accordingly, only the (E)-olefin is produced. 

The redox reaction also extends to the participation of hydroperoxides, but their efficient decomposition depends on the formation of a non-radical product such as an alcohol. Another example of a redox couple is found in the behaviour of the nitroxyl radical (R NO )- Depending on the structure of R, these are efficient radical scavengers and a redox couple between the mdical and the hydroxyl amine (R NO /R NOH) is formed (which is analogous to the galvinoxyl radical G-/GH). It is noted that the hindered amine stabilizers (e.g. Tinuvin 770 and the monomeric and polymeric analogues) are ineffective as melt antioxidants, possibly because of reaction with hydroperoxides or their sensitivity to acid. 

If such reactions were to be coupled with the photochemical generation of organic free radicals or excited molecular states before the H-atoms combined or hydride ions reacted with HaO, the presence of photore-duced products would be explained. The generation of the powerfully nucleophilic peroxy radical-ions and hydroperoxide ions (Equation 8) also could be involved in instances of the oxidative displacement of halide from aromatic rings. 

The relatively stable radicals (A) produced (e.g. phenoxyl from phenols and amin-oxyl from aromatic amines) cannot continue the kinetic chain and disappear from the system by coupling with other or the same free radicals. It should be noted that this process is stoichiometric and hydroperoxides are produced in each inhibiting step (reaction 10). 

The chemical mechanisms involved in the action of antioxidants have been discussed in a number of reviews [8,11-18] and the reader is directed to these and the references they contain for more detailed information. Two complementary antioxidant mechanisms are frequently used synergistically in polyolefins. The first is the kinetic chain-breaking hydrogen donor process, (CB-D) summarised in reaction (3). The relatively stable radicals (A) produced (e.g. phenoxyl from phenols and aminoxyl from aromatic amines) carmot continue the kinetic chain and disappear from the system by coupling with other or the same free radicals. However, it should be noted that this process is stoichiometric and hydroperoxides... 

More recent reports in 2012 and 2013 focus on the use of more sustainable metals such as iron in these cases an oxidant is required. Two equivalents of tert-butyl hydroperoxide (TBHP) for example were used with 2.5 mol% FeCla. In times as short as 1 h, in acetonitrile at 85 °C, various aliphatic and aromatic aldehydes were able to be oxidatively amidated to the corresponding amides with a range of secondary and tertiary amines. Similar work has been done by De Luca and co-workers using TBHP as an oxidant in combination with either an FeCls or Cu(OAc)2 catalyst. However, in both cases, iV-chloroamines had to be formed in situ in order to generate the required amino radical coupling partner. 

Such solvent-derived radicals can induce the decomposition of the hydroperoxide or react with oxygen in the system to form peroxidic solvent molecules. They may also react with other radicals either by coupling or disproportionation. 

The synthesis of mixed peroxides formed from /-butyl hydroperoxide and carbon-centred radicals has been studied. The reactions were strongly effected by solvents as well as catalytic amounts of Cun/Fem. The kinetic data suggest that the conditions for the Ingold-Fischer persistent radical effect are fulfilled in these cases.191 The use of Cu /Cu" redox couples in mediating living radical polymerization continues to be of interest. The kinetics of atom-transfer radical polymerization (ATRP) of styrene with CuBr and bipyridine have been investigated. The polymer reactions were found to be first order with respect to monomer, initiator and CuBr concentration, with the optimum CuBr Bipy ratio found to be 2 1.192 In related work using CuBr-A-pentyl-2-... 

---