Epoxide bromohydrin

Laboratory scale bromination of alkenes in homogeneous solution using an undivided cell is adaptable to the formation of epoxides, bromohydrins or dibromides depending on the conditions [64]. Epoxides are generated using an initially neutral solution and a low concentration of bromide ions. The reaction sequence is similar to that of Scheme 2.3. Formation of bromohydrins requires dilute hydrobromic acid as the supporting electrolyte. Dibromides are obtained using a concentrated solution of sodium bromide as electrolyte. 

Torii S, Uneyama K, Tanaka H, Yamanaka Y, Yasuda T, Ono M, Kohmoto Y (1981) Efficient conversion of olefins into epoxides, bromohydrins, and dibromides with sodium bromide in water-organic solvent electrolysis. J Org Chem 48 3312-3315... 

Several cortisone derivatives with glucocorticoid effects are most active, if they contain fluorine in the 9or-position together with an Il(9-OH group. Both substituents are introduced by the cleavage of a 9,11 -epoxide with hydrogen fluoride. The regio- and stereoselective formation of the -epoxide is achieved by bromohydrination of a 9,11-double bond and subsequent alkali treatment (J. Fried, 1954). 

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. 

We saw in Section 7.8 that bromohydrins are converted into epoxides when treated with base. Propose a mechanism, using curved arrows to show the electron flow. 

Show the stereochemistry of the epoxide (see Problem 11.42) you would obtain by formation of a bromohydrin from frnm-2-butene, followed by treatment with base. 

The influence of 1,2-asymmctric induction on the exchange of diastereotopic bromine atoms has also been investigated22,23. Thus, treatment of the / -silyloxydibromo compound 15 with butyllithium at — 110°C in the presence of 2-methylpropana led to products 17-19 after the reaction mixture was warmed to 20 °C. The distribution of the products indicates that the diastereomeric lithium compounds 16 A and 16B were formed in a ratio of 84 16, with 16A being kinetically favored by 1,2-asymmetric induction. Formation of the m-configurated epoxide (cis,anti-18) was slowed to such an extent that its formation was incomplete and a substantial amount of the parent bromohydrin 17 remained. The analogous m.yyn-configurat-ed epoxide was not observed. Presumably for sterie reasons, the parent bromohydrin did not cyclize to the epoxide but instead led to the ketone 1923. 

In the first example the product from the reaction can be controlled by choice of reaction conditions. Low temperatures and concentrated HBr give the dibromo products whilst high temperatures and lower concentrations of HBr favour the bromohydrin. Treatment of the latter intermediate with alkali gives the epoxide (ref. 3). 

Li2[NiBr4] in THF regioselectively cleaves epoxides to give bromohydrins in high yield.1136 The Br atom is predominantly found at the less-hindered carbon. 

The anti stereospecificity of epoxidation by the peracid is interpreted as due to association of the reagent with the allylic hydroxyl group which directs the entering oxygen atom to the same face of the molecule. The stereospecificity of bromohydrin formation is explicable in terms of steric approach control involving initial attack of the bulky bromine atom on the face opposite to the benzylic hydroxyl group (7). 

The hydroboration of 3o -, 3jS-, 6o -, and 6/3-methoxyandrost-4-enes (75)-(78) has been shown to proceed predominantly trans to the MeO group, which parallels the behaviour of the corresponding alcohols. With 6-OMe derivatives (77) and (78), a small amount of Markovnikov hydration, giving 5-alcohols, has been observed. Epoxidation, osmylation, and bromination of 5/3-androst-3-enes (79) have been found to take place from the /3-face in the last reaction, diequatorial dibromide and bromohydrin accompany the axial addition products." ... 

In bromohydrins, hydrogenation over Raney nickel may lead to epoxides rather than to alcohols since regular Raney nickel contains enough alkali to cause dehydrobromination. Pure hydrogenolysis of bromine can be achieved over Raney nickel which has been washed free of alkah by acetic acid [631]. 

Pulse radiolysis experiments have shown that "OH radical adds preferentially at C5 of the uracil moiety, giving rise to the reducing 5-hydroxy-5,6-uracil-6-yl radical. Interestingly, the two cis diastereomers of 6-hydroperoxy-5-hydroxy-5,6-dihydrouridine, two of the expected final products of the latter radicals in aerated aqueous solutions, have been prepared by trifluoroacetic acid treatment of uridine (3, R = H, = ribose) in the presence of H202 (equation 14). The mechanism of the reaction that involves transient formation of an epoxide-type intermediate followed by nucleophilic attack by a perhy-droxyl group at C6 presents similarities with the substitution of thymine bromohydrin by... 

Reduction of the 19-tosylates (28) and (30) with lithium aluminium hydride gave the 5,10-methano-compound (29) and the alcohol (31) respectively. Vicinal dibromo-steroids are converted readily into olefins when treated with silver salts in the presence of amines. Diaxial bromohydrins are converted into the epoxides under these conditions. 

In the realm of hydrolytic reactions, Jacobsen has applied his work with chiral salen complexes to advantage for the kinetic resolution of racemic epoxides. For example, the cobalt salen catalyst 59 gave the chiral bromohydrin 61 in excellent ee (>99%) and good yield (74%) from the racemic bromo-epoxide 60. The higher than 50% yield, unusual for a kinetic resolution, is attributed to a bromide-induced dynamic equilibrium with the dibromo alcohol 62, which allows for conversion of unused substrate into the active enantiomer <99JA6086>. Even the recalcitrant 2,2-disubstituted epoxides e.g., 64) succumbed to smooth kinetic resolution upon treatment with... 

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