Stereospecific reactions bromohydrins

The configuration of the erythro- and /Areo-bromohydrins (221) may be established by virtue of their stereospecific reaction with hexafluoroacetone to give 1,3-dioxolans (222). ... 

Overall, the stereospecificity of this method is the same as that observed in per-oxy acid oxidation of alkenes. Substituents that are cis to each other in the alkene remain cis in the epoxide. This is because formation of the bromohydrin involves anti addition, and the ensuing intranolecular- nucleophilic substitution reaction takes place with inversion of configuration at the carbon that bear s the halide leaving group. 

Next, the bromohydrin is treated with base and an intramolecular S 2 reaction (Chapter 17) closes the epoxide ring. This too is stereospecific and the major isomer only is shown. The mixture of epoxides is a result of the E/Z-alkene mixture. Potassium carbonate is too weak a base to generate much of the alkoxide anion but the cyclization may still go this way in methanol. In Chapter 41 you will learn of an alternative type of catalysis by weak bases. 

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. 

Bromohydrins. Dalton et al. have prepared bromohydrins by reaction of olefins with NBS in aqueous DMSO. The reaction involves stereospecific Markownikoff addition thus trans-1 -phenyl-1 -propene is converted into erythro-2-bromo-1 -phenylpropanol in 92% yield. The exact nature of the reagent is not... 

Two chemical syntheses of stereospecifically labeled serines (91, 92) relied on the stereospecific reduction of the acetylene 76 followed by anti addition of MeOBr (91) or HOBr (92) to the product 77. The second of these syntheses (92) is shown in Scheme 21. It involved catalytic reduction of the anthracene adducts of the propiolates 76, Ha = H, and 76 with hydrogen and deuterium, respectively, followed by a retro Diels-Alder reaction. The products were the (Z)-isomer 77, Ha = H, and the (f)-isomer 7, Hg = H, respectively. Reaction of these with Af-bromosuccinimide in sulfuric acid gave three parts of the bromohydrins 78 together with one part of the alternative regioisomers. 

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. 

Reaction of hexafluoroacetone with erythro- or /Arco-5-bromo-octan-4-ol (see Scheme 37) has been shown by F n.m.r. analysis to proceed in highly stereospecific fashion (>97%) and thereby to provide the prototype of a method for establishing bromohydrin, and hence alkene, geometries. ... 

Describe the stereochemistry of the bromohydrin formed in each reaction (each reaction is stereospecific). 

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... 

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