Bromonium ions, loss

Both proton loss and rearrangement reflect the greater positive charge at carbon in a chloronium ion than in a bromonium ion because of the weaker bridging by chlorine. 

NBS is a source of Br+. It reacts with alkenes to give bromonium ions. Then both C-Br bonds need to be replaced by C-0 bonds by single inversions, since the trans stereochemistry of the double bond is retained in the epoxide. Under these acidic conditions the bromonium ion is opened intramolecularly by the acid carbonyl O, with inversion at one center loss of H+ gives a bromolactone. 

A common feature of the compounds that give extensive syn addition is the presence of at least one phenyl substituent on the double bond. The presence of a phenyl substituent diminishes the strength of bromonium ion bridging by stabilizing the cationic center. A weakly bridged structure in equilibrium with an open benzylic cation can account for the loss in stereospecificity. 

Protons are even smaller than F+, so they should give open transition states and nonstereoselective additions, which have been confirmed experimentally.126 A loss of stereoselectivity can even be observed during the bromination of certain substituted alkenes. The HOMO, and hence the bromonium ion, are dissymmetric and an equilibrium can be established with the open form. In some cases, such as the benzylic cation below, this form dominates. 

Loss of (C4H9)-from the molecular ion of rans-4- -butylcyclohexyl bromide at 10ps—Ins has been shown to proceed at higher rates than the corresponding loss from the molecular ion of the cis isomer [336]. The difference was interpreted in terms of a concerted reaction forming a cyclic bromonium ion. The comparison of rates is intermol-ecular, however, so that the differences could stem from differences in internal energy, P(E). 

Alkene oxymercuration is closely analogous to halohydrin formation. The reaction is initiated by electrophilic addition of (mercuric) ion to the alkene to give an intermediate mercurinium ion, whose structure resembles that of a bromonium ion (Figure 7.5). Nucleophilic attack of water, followed by loss of a proton, then yields a stable organomercury addition product. The final step, reaction of the organomercury compound with sodium boro-hydride, is not fully understood but appears to involve radicals. Note that... 

The mechanism of bromination is discussed more fully in Section 5.3, but the fundamental cause of the stereospecificity is the involvement of the positively charged bromonium ion intermediate. The bromonium ion is opened by an anti approach of the bromide, leading to net anti addition. Entry 1 in Scheme 2.7 illustrates this behavior. Stereoisomeric products are obtained from the E- and Z-isomers, both as the result of anti addition. Stereospecificity is diminished or lost when the bromonium ion is not the only intermediate in the reaction. Entry 2 in Scheme 2.7 shows this behavior for cw-stilbene in nitromethane, where most of the product is the result of syn addition. The addition is anti in less polar solvents such as cyclohexane or carbon tetrachloride. The loss of anti stereospecificity is the result of a change in mechanism. The polar solvent permits formation of a carbocation intermediate. If the bromonium ion can open to a carbocation, a mixture of syn and anti products is formed. In the stilbene case, the more stable anti product is formed. Some loss of stereospecificity is also observed with 1-phenylpropene, where the phenyl group provides stabilization of an open carbocation intermediate. Part of the product from both isomers is the result of syn addition. 

This suggests that the cis bromide is the kinetic product and the more stable trans compound is the thermodynamic product, formed by reversible loss of bromide and reformation of the bromonium ion. 

The stereochemistry of a solvolysis reaction can be affected if the substrate has a substituent that can donate a pair of electrons to the developing carbocation center. For example, treatment of ( )-t/zreo-3-bromo-2-butanol (19) with HBr gave only the racemic 2,3-dibromobutane (20). There was none of the meso compound that would have been expected if the reaction involved protonation, loss of water, and formation of a free carbocation intermediate. Similarly, reaction of ( )-eri/tizra-3-bromo-2-butanol with HBr gave only meso-2,3-dibromobutane. The reaction of 19 seems best explained by nucleophilic participation of the bromine on the adjacent atom in concert with departure of the water. The result is a bridged intermediate (21) that is the same bromonium ion expected from the electrophilic addition of Br2 to cis-2-butene (Figure 8.13). Back-side attack by bromide ion on either carbon atom involved in the three-membered bromonium ring is equally likely, so a racemic mixture results. 

Chiral bromohydrin derivatives reacted under acidic conditions with very high stereoselectivity (essentially stereospecific). This points to a mechanism involving a chiral bromonium ion as the reactive intermediate. The protonation of chloroethane by the carborane superacid H(CHBuClii) proceeds via a shared-proton intermediate that decays by HCl loss to form the carbocation-like ethyl carborane. This reacts with a second EtCl to form the Et2Cl+ cation. The transannular electrophilic bromination of a polycyclic system with two C=C in close proximity was studied by computational methods. The initial bromonium was found to rearrange into more stable carbocations through reaction with the nearby carbon—carbon double bond. 

An explanation for the observed stereochemistry of alkene addition came in 1937 with the suggestion that the reaction occurs through an intermediate bromonium ion (R2Br" ), formed hy electrophilic addition of Br" " to the alkene. (Similarly, a chloronium ion contains a positively charged, divalent chlorine, R2C1. ) The bromonium ion is formed in a single step hy interaction of the alkene with Br2 and simultaneous loss of Br (Figure 8.1). 

We know that in the second step of this addition reaction, a nucleophile will attack the bromonium ion. Of the two nucleophiles present, the carbonyl oxygen is better positioned than the bromide ion to attack the back side of the bromonium ion, resulting in a compound with the observed configuration. Loss of a proton forms the final product of the reaction. 

Toluene-p-sulphonic acid monohydrate promotes hydration of imine double bonds, providing a method for the ready regeneration of ketones from their 2,4-dinitrophenylhydrazones this method is unsuitable for regeneration of a S-unsaturated ketones, where extensive retro-aldol fragmentation occurs. Imines can be oxidized photochemically to ketones. In a re-investigation of the acid-catalysed conversion of ew-bromonitro-compounds into ketones, loss of a bromonium ion followed by a Nef reaction is postulated (Scheme 70). ... 

Anft -attack by the oxygen of a molecule of water follows. The two carbons of the bromonium ion rings are similar but not identical One is closer to the methyl group than the other. Therefore, both positions will be reactive, but not equally so, producing two regioisomers. After proton loss, the ultimate result is four isomeric products (each formed as a racemate) ... 

Craft and Gung developed a paUadium-catalyzed transannular [4+3] cycloaddition route in which all of the rings of cortistatins are prepared in one step from a single macrocyclic precursor (Scheme 19.50) [114]. Exposure of macrocyclic allene 233 to a catalytic amount of palladium (II) acetate in the presence of excess lithium bromide resulted in the formation of 238 as a single isomer in 37% yield. This is the first report of a transannular [4+3] cycloaddition. The proposed mechanism is shown in Scheme 19.50. The formation of allene-palladium complex 234 affords a a-allylpalladium intermediate, which rapidly isomerizes to the 7i-allylpalladium intermediate 235. This can then undergo intramolecular cycloaddilion via an endo (compact) transition strucmre 236 to give bromonium ion 237. The loss of a proton results in the formation of the observed product 238. Cycloadduct 238 was readily converted into the tetracyclic core skeleton of cortistatins 239 by selective reduction of the olefin formed by cycloaddition with furan, followed by reductive debromination. 

The first step in the mercuric-ion-catalyzed hydration of an alkyne is formation of a cyclic mercurinium ion. (Two of the electrons in mercury s filled 5d atomic orbital are shown.) This should remind you of the cyclic bromonium and mercurinium ions formed as intermediates in electrophilic addition reactions of alkenes (Sections 4.7 and 4.8). In the second step of the reaction, water attacks the most substituted carbon of the cyclic intermediate (Section 4.8). Oxygen loses a proton to form a mercuric enol, which immediately rearranges to a mercuric ketone. Loss of the mercuric ion forms an enol, which rearranges to a ketone. Notice that the overall addition of water follows both the general rule for electrophilic addition reactions and Markovnikov s rule The electrophile (H in the case of Markovnikov s rule) adds to the sp carbon bonded to the greater number of hydrogens. 

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