Polyhalogenated substrate

Newman SG, Lautens M (2010) The role of reversible oxidative addition in selective palladium(0)-catalyzed intramolecular cross-couplings of polyhalogenated substrates synthesis of brominated indoles. J Am Chem Soc 132 11416-11417... 

The N-arylation was achieved with 0.5-1 mol% catalyst and CSjCOj as base in toluene. However, relatively long reaction times of 12-48 h were required to obtain high yields. The reaction could also be carried out with P(tBu)j (26) as the supporting ligand to furnish the products in sUghtly improved yields [130]. Applying this method, polycycUc, electron-rich aromatic molecules were synthesized by multiple amination of polyhalogenated substrates (Scheme 13.84). 

The Ullmann homo-coupling reaction of polyhalogenated substrates Preparation of 3,3, 5,5 -tetrabromobiphenyl-2,2 -biscarboxaldehyde (14) [14]... 

Palladium NHC systems for the hydrodehalogenation of aryl chlorides and bromides and polyhalogenated aromatic substrates originate from about the same time as the first reports on Ni chemistry, and show many similarities. Initial efforts showed that the combination of PdCdba) (2 mol%), one equivalent of imidazolium chloride and KOMe produced an effective system for the reduction of 4-chlorotolu-ene, especially upon use of SIMes HCl 2 (96% yield of toluene after 1 h at 100°C) [7]. Interestingly, higher ligand to metal ratios severely inhibited the catalysis with only 7% yield of toluene achieved in the same time in the presence of two equivalents of SIMes HCl 2. Variation of the metal source (Pd(OAc)2, Pd(CjHjCN)jClj), alkoxide (NaOMe, KO Bu, NaOH/ ec-BuOH) or imidazolium salt (IMes HCl 1, IPr HCl 3, lAd HCl, ICy HCl) all failed to give a more active catalyst. 

Fluorine has been used for the generation of extremely strong electrophilic halogenating agents in electrophilic iodination and bromination of deactivated aromatic substrates in highly acidic reacton media. Polyhalogenation of more activated aromatic substrates is also possible (Fig. 90) [231-233]. 

Polyhalogenated aromatic hydrocarbons (e.g. hex-achlorobenzene (HCB, CeCle) and polychorobiphenyls (PCBs)) are rapidly degraded by superoxide ion in DMF to bicarbonate and halide ions. Because halogen-bearing intermediates are not detected, the initial nucleophilic attack is the rate-determining step. The rates of reaction exhibit a direct correlation with the electrophilicity of the substrate (reduction potential) (e.g. CeCle, E° = -1.48 V vs. SCE ki/[S] = 1 X lO M- s and 1,2,4-C6H3C13, E° = -2.16 V ki/[S] = 2x 10-2 M- s ). 

In both imidazoles and their /V-substituted derivatives, halogenation occurs preferentially in the 4(5)-positions there is a slight preference for 5-substitution in 1-substituted substrates. Although the 2-position is much less reactive, it is difficult to prevent substitution at that site. Indeed, polyhalogenation is so facile that it is seldom feasible to make monohalogenated imidazoles directly. Both sodium hypochlorite and NCS convert imidazole into its 4,5-dichloro derivative contaminated by the 2,4,5-trichloro product. Even very mild conditions are unlikely to promote monochlorination, and bromination and iodination arc similar. Mechanisms can vary, however, from substrate to substrate. It is likely that C-2 halogenations are the result of addition-elimination [1]. 

Reductive biotransformations of several compounds such as polyhalogenated, keto, nitro and azo derivatives, are catalysed by a variety of enzymes which differ according to the substrates and the species. The liver cytochrome P-450-dependent drug metabolizing system is capable of reducing Af-oxide, nitro and azo bonds, whereas the cytosolic nitrobenzene reductase activity is mainly due to cytochrome P-450 reductase, which transforms nitrobenzene into its hydroxylamino derivative. NADPH cytochrome c reductase is also able to catalyse the reduction of nitro compounds. These metabolic conversions may also be brought about by gastrointestinal anaerobic bacteria. 

The purpose of this chapter is to give an overview of the chemical and biological processes that control the reactivity of Fe(II) in heterogeneous aqueous systems with respect to pollutant transformation. To this end, we will evaluate data collected in various laboratory systems as well as field studies. Two classes of model compounds with complementary properties will be used to monitor the reactivity of Fe(II) species in the various systems. Nitroaromatic compounds (NACs) primarily served to characterize the systems in terms of mass and electron balances. Reduction of NACs by Fe(II) species results in only a few major products (aromatic amines and hydroxy-lamines) which can be easily quantified by standard HPLC-UV methods in the low liM range. Polyhalogenated aliphatic compounds (PHAs) were used if little perturbation of the systems in terms of electron transfer to the organic substrates was crucial. Reduction of PHAs requires fewer electrons than nitro reduction and PHAs can be quantified by standard GC-ECD methods in the low ppb range. 

In these constrained molecules, the Favorskii rearrangement leads essentially to the ring-contracted acid or ester in good yields. However, the formation of ring-opened products has been reported when polyhalogenated strained ketones react according to the quasi-Favorskii mechanism. Results using this type of substrate are reported in Table 8. 

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