Bromonium ions bromohydrins from alkenes

The serendipitous event that inspired the development of NPGs (see Sect. 2.1) was the attempt to prepare a bromohydrin from alkene 4 (Scheme 1) [6, 19]. With the benefit of hindsight, we now realize that this objective was predestined to fail, because the first-formed cyclic bromonium ion, e.g., 15 (Scheme 4), would undergo facile R05 interaction [26] to give a furanylium ion, 16, and thence the oxocarbe-nium ion 17. The latter would be scavenged by water to give 18 (R =H), the product of oxidative hydrolysis. 

Brown s result was supported by later experiments in which bromonium ions were generated by bubbling gaseous hydrobromic acid through a solution of bromohydrins in halogenated solvents. Under these conditions, bromine is eliminated as it is formed, so that the resulting alkene is observed directly (Scheme 15). This method has been applied to the bromohydrins derived from cis- and trans-stilbenes (Scheme 16) and from 5//-dibenzo[a,d]-cycloheptene and -azepine systems ([29a] and [29b] respectively Scheme 17), in which steric constraints should favour elimination (path a) as against substitution (path b). 

Stereoselectivity comes from a stereospecific syn or anti addition to an alkene of fixed and known geometry. These last reactions, applied to cyclohexene, lead to anti bromohydrin 14 while epoxidation occurs stereospecifically and syn. It doesn t matter which end of the epoxide 12 or bromonium ion 13 is attacked by the nucleophile anti addition occurs in both cases since inversion is demanded by the mechanism of the SN2 reaction. Cyclohexene must be Z but in open chain compounds syn addition to the -isomer would lead to the same diastereoisomer of the product as anti addition to the Z-isomer. In this chapter we explore more advanced versions of these reactions in which usually several types of selectivity will be combined and show how they are used in synthesis. 

From a synthetic point of view, the participation of water in brominations, leading to bromohydrins, is probably the most important example of nucleophilic participation by solvent. In the case of unsymmetrical alkenes, water reacts at the more substituted carbon, which is the carbon with the greatest cationic character. If it is desired to favor introduction of water, it is necessary to keep the concentration of the bromide ion as low as possible. One method for accomplishing this is to use N-bromosuccinimide (NBS) as the brominating reagent. High yields of bromohydrins are obtained by use of NBS in aqueous DMSO. The reaction is a stereospecific anti addition. As in bromination, a bromonium ion intermediate can explain the anti stereospecificity. It has been shown that the reactions in dimethyl... 

The creation of a bromonium ion in alkene brominations suggests that, in the presence of other nucleophiles, competition might be observed in the trapping of the intermediate. For example, bromination of cyclopentene in water as solvent gives the vicinal bromoalcohol (common name, bromohydrin). In this case, the bromonium ion is attacked by water, which is present in large excess. The net transformation is the anti addition of Br and OH to the double bond. The other product formed is HBr. The corresponding chloroalcohols (chlorohydrins) can be made from chlorine in water through a chloronium ion intermediate. 

Another unique and indirect method for constructing halogenated carbocycles has been demonstrated by Brad-dock and co-workers (Scheme 43.36). It is generally accepted that the generation of enantiomeiicaUy pure bro-monimn ions from olefins by asymmetric electrophilic bro-minations is problematic as a result of the intervention of rapid bromonium ion-alkene exchange that causes erosion of the enantiomeric purities of the ions. Braddock et al. showed that enantio-pure bromonium ions are generated stereospecifically from chiral bromohydrin derivatives 210 (84% ee) and 212 (86% ee). Subsequent trapping of cationic species 211 with its nucleophilic counterpart produced... 

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