Bromonium ions as intermediates in stereoselective synthesis

You wiU not be surprised to learn that the other nucleophiles (water and alcohols) you saw intercepting bromonium ions earlier in the chapter also do so stereospecifically. The following reaction can be done on a large scale, and produces a single diastereoisomer of the product (racemic, of course) because water opens the bromonium ion with inversion. 

The reagent used to form the bromonium ion here is not bromine, and may be new to you. It is called N-bromosuccinimide, or NBS for short Unlike the noxious brown liquid bromine, NBS is an easily handled crystalline solid, and is perfect for electrophilic addition of bromine to alkenes when the bromonium ion is not intended to be opened by Br . It works by providing a very small.concen-tration of Br2 in solution a small amount of HBr is enough to get the reaction going, and thereafter every addition reaction produces another molecules of HBr which liberates more Br2 from NBS. In a sense, NBS is a source of Br . 

With NBS, the concentration of Br is always low, so alcohols compete with Br to open the epoxide even if they are not the solvent. In the next example, the alcohol is propargyl alcohol , prop-2-yn-l-ol. It gives the expected unfi-disubstituted product with cyclohexene and NBS. 

To finish our discussion of bromonium ions, you need to know about one more important class of reactions, those in which the nucleophile is located within the same molecule as the bromonium ion. Here is an example the nucleophile is a carboxylate, and the product is a lactone (a cyclic ester). This type of reaction—the cyclization of an unsaturated acid—is known as a bromolactonization. Intermolecular attack on the bromonium ion by bromide ion does not compete with the intramolecular cyclization step. 

Every example of electrophilic addition of a halogen to an alkene that we have shown you so far has been with bromine. This is quite representative bromine is the most widely used halogen for electrophilic addition, since its reactivity is second only to iodine, yet the products are more stable. However, in these lactonization reactions, iodine is the more commonly used reagent, and the products of iodolactonizations are important intermediates (you will meet them again in Chapter 33). In the next example, the iodolactonization product is treated with sodium methoxide, which appears (a) to hydrolyse the lactone, and (b) to substitute the iodide for OMe. In fact, there is a little more to this than meets the eye. 

When 1-methylcyclohexene is used as the starting material, there is additionally a question of regioselectivity. The alcohol attacks the more hindered end of the bromonium ion—the end where there can be greatest stabilization of the partial positive charge in the loose transition state. This reaction really does illustrate the way in which a mechanism can lie in between S l and S j2. We see a configurational inversion, indicative of an S j2 reaction, happening at a tertiary centre where you would usually expect S jl. 

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