Electrophilic halogenating species

In vanadium-dependent haloperoxidases, the metal center is coordinated to the imidazole system of a histidine residue, which is similarly responsible for creating hypochlorite or hypobromite as electrophilic halogenating species [274]. Remarkably, a representative of this enzyme class is capable of performing stereoselective incorporation of halides, as has been reported for the conversion of nerolidol to various snyderols. The overall reaction commences through a bromonium intermediate, which cyclizes in an intramolecular process the resulting carbocation can ultimately be trapped upon elimination to three snyderols (Scheme 9.37) [275]. 

Formation of the electrophilic halogen species leads to the potential for rapid reaction with compounds containing strongly activating groups, such as activated aryl compounds. Particularly, substances containing aromatic ring structures that have... 

Haloperoxidases catalyze the hydroperoxide-dependent oxidation of Cl-, Br- and/or I to electrophilic halogenating species that halogenate organic substrates (equation 1). As predicted by the relative ease of oxidation of halide ions (I- > Br- > Cl" >> F-), chloroper-oxidases oxidize Cl-, Br- and I-, bromoperoxidases oxidize Br- and I-, iodoperoxidase oxidize only I- while no peroxidase can oxidize F-14. 

The stereoselectivity observed in the cyclization of 4-unsaturated amides is dependent on the electrophilic halogen species. With /V-chlorosuccinimide the trans/cis ratio is reduced to 3 2, while with A -bromosuccinimide the fra .v-isomer is obtained in >98% purity. The structures of the iodolactones 4 were confirmed by reduction with tributyltin hydride to the trans- and rw-2.4-dimethy]-y-lactones. The high 1,3-trans selectivity strongly contrasts with the results obtained when 2-methyl-4-pentenoic acid is cyclized under thermodynamic conditions with iodine in acetonitrile. In this case a 92% yield and a 32 68 mixture of the f/ww/m-com pounds was obtained. 

Biosynthetic halogenation can occur through multiple pathways, but many halogenase enzymes use electrophilic halogenating species that are produced by oxidation of halide ions. 

In o-carborane (1, Figure 6.1), boron atoms 9 and 12 are the most electron-rich atoms followed by boron atoms 8 and 10 whereas boron atoms 3 and 6, which are adjacent to the two carbon atoms, have the highest electron deficiency (Grimes, 1970). Therefore, substitution reactions of t)-carborane with electrophilic halogen species preferentially take place at the boron atoms 8, 9, 10, and 12 (Grimes, 1970). 

In OT-carborane (2, Figure 6.1), boron atoms 9 and 10 have the highest electron density and are therefore most susceptible to electrophilic halogenation (Grimes, 1970). However, m-carborane (2) is in general far less reactive toward electrophilic halogen species than o-carborane (1). Iodination and bromination of 2 is 11 and 7 times, respectively, slower than for 1 (Grimes, 1970). 

As with chlorine-containing oxidants, JV-bromo species have been used to oxidize sulphoxides to sulphones (with no bromine incorporation) through the initial formation of a bromosulphonium ion, by nucleophilic attack of the sulphoxide sulphur atom on the electrophilic halogen atom. Such reactions involve JV-bromosuccinimide ° bromamine-T, iV-bromoacetamide ° and iV-bromobenzenesulphonamide. All reported studies were of a kinetic nature and yields were not quoted. In acid solution all oxidations occurred at or around room temperature with the nucleophilic attack on the electrophilic bromine atom being the rate-limiting step. In alkaline solution a catalyst such as osmium tetroxide is required for the reaction to proceed . ... 

Radioiodination involves the substitution of radioactive iodine atoms for reactive hydrogen sites in target molecules. The process usually involves the action of a strong oxidizing agent to transform iodide ions into a highly reactive electrophilic iodine II compound (typically I2 or a mixed halogen species such as IC1). Formation of this electrophilic species leads to the potential for rapid iodination of aromatic compounds... 

The reaction of IODO-GEN with iodide ion in solution results in oxidation with subsequent formation of a reactive, mixed halogen species, IC1 (Fig. 266). Either 125I or 13 1 can be used in this reaction. The IC1 then rapidly reacts with any sites within target molecules that can undergo electrophilic substitution reactions. Within proteins, any tyrosine and histidine side-chain groups can be modified with iodine within... 

Monohalogenated products are obtained by treatment of this heterocycle (20) with elemental halogens (bromine, chlorine, or iodine) in concentrated sulfuric acid containing silver sulfate. This acidic reaction medium aids electrophilic attack by the positive halogen species on a protonated thienopyridine. Subsequently, nonacidic conditions have been identified for the monobromination reaction <74JHC205>. Monobromination of the isomers (21) and (23) has also been reported <70AK(32)249>. 

A large number of halogenated cyclopropanes have been converted to cyclopropyl sulfides (Table 14) there is one example of the formation of a sulfinic acid. A variety of methods have been used utilizing both nucleophilic and electrophilic cyclopropane species and there are also the possibility of carrying out formal substitution by elimination/addition reactions. 

Lithio-heterocycles have proved to be the most useful organometallic derivatives they react with the whole range of electrophiles in a manner exactly comparable to that of aryllithiums and can often be prepared by direct metallation (C-hydrogen deprotonation), as well as by halogen exchange between a halo-heterocycle and an alkyllithium. As well as reaction with carbon electrophiles, Uthiated species are often the most convenient source of heterocyclic derivatives of less electropositive metals, such as zinc, boron, silicon and tin, as will be seen in the following sections. 

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