Bromohydrin, regioselective formation

Fig. 3.43. Stereo- and regioselective formation of a bromohydrin from a 1,2-disub-stituted alkene.

The diastereoselective halohydrin formation, resulting from the reaction of chiral /V -enoyI -2-oxazoI idinones with Br2/l2 and water, promoted in the presence of silver , in aqueous organic solvents, has been found to occur with high regioselectivity and moderate to good diastereoselectivities. The alkenoyl, cinnamoyl, and electron-deficient cinnamoyl substrates readily produced the bromohydrin in aqueous acetone, but no iodohydrin formation was observed under these conditions. On the other hand, ( ) electron-rich cinnamoyl substrates preferred to afford iodohydrins in aqueous acetone with moderate diastereoselectivity enhanced diastereoselectivity was observed for aqueous THF.31... 

With NBS in aqueous DMSO, cyclohexene gives racemic /ra/ -2-bromo-1 -cyclohexanol. This stereochemical result means that we have a Irans-addition. In the analogous bromohydrin formation from 3,3-dimethylcyclohexene, the analogous dimethylated 2-bromo-l-cyclohexanol is also produced /ra/rv-selectively as well as regioselectively (Figure 3.43). In the bromo-nium ion intermediate, the H20 molecule does not react at the hindered neopentyl center. This is as expected from the rules for SN2 reactivity (Section 2.4.4), and results in high regioselec-tivity. 

The cationic intermediates also can be captured by solvent. Halogenation with solvent capture is a synthetically important reaction, especially for the preparation of chlorohydrins and bromohydrins. Chlorohydrins can be prepared using various sources of electrophilic chlorine. Chloroamine T is a convenient reagent for chloro-hydrin formation. Bromohydrins are prepared using NBS and an aqueous solvent mixture with acetone or THF. DMSO has also been recommended as a solvent. These reactions are regioselective, with the nucleophile water introduced at the more-substituted position. 

The argument is closely analogous to that used to explain the regioselectivity of formation of bromoacetoxy compounds (Table 9.2) formed in the addition of bromine to alkenes in acetic acid. Similarly, addition of bromine to alkenes in water produces bromohydrins. Although they are more difficult to synthesize, iodohydrins and fluorohydrins are also known. For a review of the synthesis and reactions of halohydrins, see Rosowsky, A. in Weissberger, A., Ed. Heterocyclic Compounds with Three- and Four-Membered Rings, Part One Wiley-Intersdence New York, 1964 p.l. 

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