Radical-mediated dehalogenation

Pletcher and associates [155, 159, 160] have studied the electrochemical reduction of alkyl bromides in the presence of a wide variety of macrocyclic Ni(II) complexes. Depending on the substrate, the mediator, and the reaction conditions, mixtures of the dimer and the disproportionation products of the alkyl radical intermediate were formed (cf. Section 18.4.1). The same group [161] reported that traces of metal ions (e.g., Cu2+) in the catholyte improved the current density and selectivity for several cathodic processes, and thus the conversion of trichloroacetic acid to chloroacetic acid. Electrochemical reductive coupling of organic halides was accompanied several times by hydrodehalogena-tion, especially when Ni complexes were used as mediators. In many of the reactions examined, dehalogenation of the substrate predominated over coupling [162-165]. 

As indicated in Chapter 8, the production of alkanes, as by-products, frequently accompanies the two-phase metal carbonyl promoted carbonylation of haloalkanes. In the case of the cobalt carbonyl mediated reactions, it has been assumed that both the reductive dehalogenation reactions and the carbonylation reactions proceed via a common initial nucleophilic substitution reaction and that a base-catalysed anionic (or radical) cleavage of the metal-alkyl bond is in competition with the carbonylation step [l]. Although such a mechanism is not entirely satisfactory, there is no evidence for any other intermediate metal carbonyl species. 

In several examples the reductive halide-hydrogen exchange has been studied on a preparative scale. For example, the indirect electroreduction of 2-chloropyridine in DMF using anthracene as mediator gives pyridine in 83-86 % yield 2 . For the dehalogenation of 1-chlorohexane (80% yield), naphthalene is applied as redox catalyst. Similarly, 6-chloro-hexene yields 1-hexene (60%) and methylcyclopentane (25%), which is the product of the radical cyclization . The indirect electrochemical reduction of p- and y-bromocarboxylic esters forms coupling and elimination products besides the dehalogenated products... 

In Chapter 4, we saw that Sml2 mediates the dehalogenation of a range of alkyl halides. These reactions proceed by reduction to alkyl radicals that are then... 

Miura et al. built on Ryu s previous work to achieve four-component radical cascades leading to diketones (Scheme 63) [174]. This outstanding result relies on initial carbonylation of alkyl radicals to form acyl radicals, such as 196. The nucleophilicity of acyl radicals allowed them to react with electron-deficient olefins to form ct-cyano radicals (197), whose phihcity is now reversed. Thus, they were able to add onto stannyl enolates and led to ketyl radicals such as 198. Those latter radicals underwent / -elimination of trib-utylstannyl radicals. This key elimination regenerated the mediator for the initial dehalogenation. This very fine tuning of the radical reactivities is the key element that makes the whole process work. 

Direct photoreactions are mediated by halocarbon excited state(s) that react to form products. Dehalogenations can involve either photohydrolysis (i.e., photonucleophilic replacement of halogen by OH) or homolysis of the carbon-halogen bond to form free radicals. Photohydrolysis is the most important dehalogenation pathway for aromatic halocarbons. 

Dehalogenation. The NBS-mediated radical side-chain bromination of (V,(V-di-ierf-butoxycarbonyl-protected phenylalanine, tyrosine, histidine, or tryptophan and subsequent treatment with AgNOs in acetone provide the frans-oxazolidinones predominantly, which are then converted to the 8-hydroxy amino acid derivatives in excellent overall yield. a-Bromo esters can be transformed to nitrate esters by treatment with AgNOs in acetonitrile. The subsequent oxidation with NaOAc/DMSO gives the corresponding glyoxylate esters. This strategy has been successfully applied into the total synthesis of macrocyclic (+)-brefeldin... 

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