Bromonium intermediate

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]. 

Reversible formation of ionic intermediates in halogenated solvents has been suggested to be due to the weakly nucleophilic character of the counteranion, the tribromide ion, which should dissociate into nucleophilic bromide and free bromine before reacting with the bromonium ion (refs. 11,25,26). In order to check this hypothesis the product distribution of the c/s-stilbene bromination in chloroform was investigated (ref. 27). In the latter solvent the formation constant of Br3 is considerably lower than in DCE, Kf = 2.77 (0.13) x 10 against > 2 x 107 M 1. (ref. 28). As a consequence, at 10 3 M [Br2] relevant amounts of bromide ions are present as counteranion of the bromonium intermediate. Nevertheless, the same trend for the isomerization of cis- to rran -stilbene, as well as an increase of... 

The reaction intermediate is a cyclic bromonium intermediate that is formed in a single step by interaction of an alkene with Br+. 

However, it is clear that during catalysis an enzyme-bound bromonium intermediate is formed which binds specifically indoles and catalyzes a regio-selective bromoperoxidative oxidation. This brown seaweed produces highly volatile and simple halohydrocarbons such as CH2Br2 and CHsBr. These halohydrocarbons are formed by reaction of enzymatically generated HOBr with organic matter that slowly decays to form these halohydrocarbons. Thus the reported oxidation of indoles is most probably not related to the known physiological role of the enzyme. 

The use of chloramine T and phenyltrimethylammonium bromide (PTAB) is expected to give the air-product. Under these conditions, the bromonium ion forms initially, followed by the attack of the nitrogen source on the bromonium intermediate. It was assumed that the bromonium ion would form on the face opposite the OR group. Backside attack of the nitrogen (air to the oxygen substituents) resulted in the formation of the ak-aziridine 27b. 

The labile bromonium intermediate should provide much more driving force for the concerted intramolecular displacement than an alternate /3-bromooxindole (Cl). This was tested by the action of NBS on ethyl carbobenzyloxy-L-2-hydroxytryptophylglycinate (C) which was cleaved in... 

In a medium of 8-10 M lithium acetate at pH 4, however, the extent of cleavage of the model peptides with both V-bromosuccinimide and V-bro-moacetamide increased markedly (Table VI). This increase in yield is probably due to the greatly decreased activity of water in concentrated salt solutions (cf. Robinson and Stokes, 1955). Under such conditions opening of the bromonium intermediate by water competes poorly with intramolecular participation of the imidole group. 

Bromine in DMF, with silver perchlorate to precipitate bromide ions, reacts with a steroidal 2-ene (81) to give the 3a-bromo-2 -formyloxy-derivative (83) in high yield the reaction provides a smooth synthesis of the 2j ,3)ff-epoxide by alkaline hydrolysis. The 2a,3a-bromonium intermediate (82), formed stereo-specifically, similarly affords the Iji-ol nitrate (84) with silver nitrate in pyridine, ... 

PROBLEM 10.68 The Halohydrin formation animation was calculated using a symmetrical alkene. The symmetry of the alkene means that nucleophilic addition to the bromonium intermediate will not be regioselective. Select play for this reaction. Stop at the first intermediate and observe the calculated LUMO. Based on this data, where is the positive charge located Show four products that would be formed through nucleo-phihc attack at each of the places of LUMO density. 

The first step is identical to what we saw just a few moments ago the alkene attacks Br2 to form a bridged, bromonium intermediate. But now we have a new possibility, because there are now two nucleophiles present bromide and water. Rather than Br attacking the bromonium ion, a water molecule can attack instead, which... 

One typical example of the occurrence of halogen braiding in a transient species is the bromination of alkenes its textbook description involves a non-covalent precursor complex 10, in which the Br-Br - alkene angle is linear (Scheme 4). Subsequently, the Br-Br bond is broken, and a bromonium intermediate 11 is created. The latter process could also be described as a debromination of the strong halogen-bond donor dibromine by the alkene, or as an X-philic [69] SN2-type reaction at bromine. 

On the other hand. Mechanism 2 proposes the displacement of a Br by nucleophilic attack of the neighboring bromine atom (neighboring group participation), and formation of a bromonium ion intermediate 4. In a second step, the teiiuride acts as a scavenger of the Br in the bromonium intermediate to yield the olefin (Scheme 29.4). In both cases, the bromotelluronium salts 5 formed at first instance, give the isolated neutral Te(IV) by-products 6 after bromide addition. 

Step 1 Reaction of ethylene and bromine to form a bromonium ion intermediate... 

Step 2 of the mechanism m Figure 6 12 is a nucleophilic attack by Br at one of the carbons of the cyclic bromonium ion For reasons that will be explained m Chapter 8 reactions of this type normally take place via a transition state m which the nude ophile approaches carbon from the side opposite the bond that is to be broken Recall mg that the vicinal dibromide formed from cyclopentene is exclusively the trans stereoisomer we see that attack by Br from the side opposite the C—Br bond of the bromonium ion intermediate can give only trans 1 2 dibromocyclopentane m accordance with the experimental observations... 

The idea that a cyclic bromonium ion was an intermediate was a novel concept when It was first proposed Much additional evidence including the isolation of a sta ble cyclic bromonium ion has been obtained since then to support it Similarly cyclic... 

In summary, it appears friat bromination usually involves a charge-transfer complex which collapses to an ion-pair intermediate. The cation can be a carbocation, as in the case of styrenes, or a bromonium ioiL The complex can evidently also be captured by bromide ion when it is present in sufficiently high concentration. 

The positive bromine which leads to bromonium ion intermediates is softer and also has unshared electron pairs which can permit a total of four electrons to participate in the bridged bromonium ion intermediate. This would be expected to lead to a more strongly bridged and more stable species than is possible in the case of the proton. The bromonium ion can be represented as having two covalent bonds to bromine and is electrophilic but not electron-deficient. 

This scheme represents an alkyne-bromine complex as an intermediate in all alkyne brominations. This is analogous to the case of alkenes. The complex may dissociate to a inyl cation when the cation is sufficiently stable, as is the case when there is an aryl substituent. It may collapse to a bridged bromonium ion or undergo reaction with a nucleophile. The latta is the dominant reaction for alkyl-substituted alkynes and leads to stereospecific anti addition. Reactions proceeding through vinyl cations are expected to be nonstereospecific. 

In order to explain the observed product, a cyclic bromonium ion intermediate has been proposed. 

How does the formation of a bromonium ion account for the observed anti stereochemistry of addition to cyclopentene If a bromonium ion is formed as an intermediate, we can imagine that the large bromine atom might "shield" one side of the molecule. Reaction with Br ion in the second step could then occur only from the opposite, unshielded side to give trans product. 

We saw in the previous section that when Br2 reacts with an alkene, th cyclic bromonium ion intermediate reacts with the only nucleophile presen Br- ion. If the reaction is carried out in the presence of an additional nuclec phile, however, the intermediate bromonium ion can be intercepted by th added nucleophile and diverted to a different product. In the presence of watei for instance, water competes with Br- ion as nucleophile and reacts with th bromonium ion intermediate to yield a broinohydrin. The net effect is additioi of HO-Br to the alkene by the pathway shown in Figure 7.1. 

Mechanism of bromohydrin formation by reaction of an alkene with Br2 in the presence of water. Water acts as a nucleophile to react with the intermediate bromonium ion. 

Reaction of the alkene with Br2 yields a bromonium ion intermediate, as previously discussed. 

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