Electrophilic Additions Involving Metal Ions

SECTION 6.4. ELECTROPHILIC ADDITIONS INVOLVING METAL IONS 

The stereochemistry of both chlorination and bromination of several cyclic and acyclic dienes has been determined. The results show that bromination is often stereo-specifically anti for the 1,2-addition process, whereas syn addition is preferred for 1,4-addition. Comparable results for chlorination show much less stereospeciftcity. It appears that chlorination proceeds primarily through ion-pair intermediates, whereas in bromina-hon a stereospecific anfi-l,2-addition may compete with a process involving a carbocation mtermediate. The latter can presumably give syn or anti product. 

Certain metal cations are capable of electrophilic attack on alkenes. Addition is completed when a nucleophile adds to the alkene-cation complex. The nucleophile may be the solvent or a ligand from the metal ion s coordination sphere. 

The best characterized of these reactions involve the mercuric ion, Hg , as the cation. The same process occurs for other transition-metal cations, especially Pd, but the products often go on to react fiirther. Synthetically important reactions involving Pd will be discussed in Section 8.2 of Part B. The mercuration products are stable, and this allows a relatively uncomplicated study of the addition reaction itself The usual nucleophile is the solvent, either water or an alcohol. The tenn oxymercuration is used to refer to reactions in 

Kitching, Organomet. Chem. Rev. 3 61 (1968) R. C. Larock, Solvomercuration/Demercuration Reactions in Organic Synthesis, Springer-Verlag, New bik, 1986. 

The product distribution can be shifted to favor the 1,2 product by use of such milder brominating agents as the pyridine-bromine complex or the tribromide ion, BrJ. It is believed that molecular bromine reacts through a cationic intermediate, whereas in the case of the less reactive brominating agents a process more like the AdeS anti-addition mechanism is involved. 

The stereochemistry of both chlorination and bromination of several cyclic and acychc dienes has been determined. The results show that bromination is often stereo-speciflcally anti for the 1,2-addition process, whereas syn addition is preferred for 1,4- 

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Pyrrole and indole rings can also be constructed by intramolecular addition of nitrogen to a multiple bond activated by metal ion complexation. Thus, 1-aminomethyl-l-alkynyl carbinols (obtained by reduction of cyanohydrins of acetylenic ketones) are cyclized to pyrroles by palladium(II) salts. In this reaction the palladium(II)-complexed alkyne functions as the electrophile with aromatization involving elimination of palladium(II) and water (Scheme 42) (81TL4277). 

Overall, many biophysical approaches have been applied to the study of catalysis by the metalloenzyme thermolysin. The metal ion was found by all studies to be involved in binding substrates and inhibitors. In addition, the x-ray structure of the protein has been useful in reaching the conclusion that the metal ion probably functions in catalysis as an electrophilic sink. ... 

The extensive data accumulated by Nakamura and Otsuka, although interpreted by them as being due to the intervention of metal carbene and metallocyclobutane intermediates, can also be rationalized by an alternative mechanism in which coordination of the chiral Co(II) catalyst with the alkene activates the alkene for electrophilic addition to the diazo compound (Scheme 5.4). Subsequent ring closure can be envisioned to occur via a diazonium ion intermediate, without involving at any stage a metal carbene intermediate. 

Oxidative addition reactions can lead to ligand replacements when followed by reductive eliminations of different groups. Electrophilic attack at the metal ion is often involved in these reactions, making a direct parallel with some of the processes already discussed and justifying concentration on the former of the two reactions. Recent work has emphasized similarities in the relationship of this family of reactions to other ligand replacement routes. 

Transfer of the methyl carbanion from methylcobalamin to Hg " " ion is non-enzymatic. Production of CH3B12 is enzyme dependent. The initial methylation of Hg " " proceeds at a rate 6000 times faster than the second methylation. In addition to electrophilic attack involving the displacement of a carbanion, two other reactions result in (To—C bond breakage are proposed. One involves displacement of a methyl radical from CH3B,2. The other is a redox switch mechanism which requires the presence of two different oxidation states of the metal. 

Based on the previous discussion and the nature of the Mo-tj -S4 chromophore, the reactions of the thio- and oxo/thiometallates mainly involve the Mo=S and M0-S2 groups and include (Figs. 20 and 21) sulfur addition reactions, sulfur abstraction reactions, addition of electrophilic molecules such as CS2 and DMA, Mo=S dimerization reactions, and abstraction of S " by thiophilic metal ions. 

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