Hydrobromination, of alkenes

Anti-Markownikoff hydrobromination of alkenes. This reaction can be carried out by hydrosilylation of an aikene followed by conversion to an organopenta-fluorosilicate, in which the C—Si bonds arc highly reactive to halogens. The method can also be used for preparation of alkenyl halides (last example). ... 

In radical chain adflitions to alkenes, the chain carrier adds to the rr bond to create the more highly substituted radical. This method allows for the anti-Markovnikov hydrobromination of alkenes, as well as the addition of thiols and some halomethanes. 

The hydrobromination of a number of halogenated alkenes has been examined. Allyl bromide reacts with HBr in the absence of peroxides, or upon addition of antioxidants121 or FeCb,61 or in acetic acid,122 to produce primarily 1,2-dibromopropane (equation 74). Allyl chloride behaves similarly.123... 

Starting with geraniol (126), Sharpless asymmetric epoxidation [68] proceeded in 95% yield and with 93% ee (see Scheme 29) [69]. Hydrobromination of the alkene was achieved under standard conditions using NBS in THF and water (5 1) to afford a 64% yield of diastereomeric bromo alcohols (127). Cyclization to the tetrahydropyran diol was accomplished by treating 127 with camphorsulphonic acid in diethyl ether, followed by diol cleavage with sodium periodate to give a mixture of aldehydes 128 and 129. Upon... 

OH/Br exchange (aq. HBr/PBr3), 303 porphyrin synthesis with, 255, 349 Hydrobromination of alkynes with Zr, 132, 325 Hydrochlorothiazide, 310 Hydrofluoric acid aq. HF) deblocking with of diol acetonides, 277 of silyl ethers, 277, 329 of silyl thioethers, 169 Hydroformylation of alkenes, 46-48 Hydrogenation, 96-105 See also Hydrogenolysis) of alkenes, 41, 96-97, 101-103, 278, 283 of alkynes to (Z)-alkenes, 40, 64,100-101... 

Since the bromine adds to the least-substituted carbon atom of the double bond, thus generating the more-substituted radical intermediate, the regiospecificity of radical-chain hydrobromination of olefins is opposite that of ionic addition. The early work on the mechanism of the reaction was undertaken to understand why Markownikoff s rule was violated under certain circumstances. Anti-Markownikoff additions were eventually traced to reaction conditions under which peroxides or light were causing initiation of the radical-chain process. The radical-chain addition of hydrogen bromide to alkenes is a synthetically useful reaction, as illustrated by entries 1, 2, and 3 in Scheme 12.5. 

Bromo-l-alkenes can be prepared regioselectively and in high yield by direct hydrobromination of terminal acetylenes with tetraethylammonium hydrogen dibromide in dichloromethane. The reagent, which is prepared in situ from tetraethylammonium bromide and hydrogen bromide, also hydro-brominates acetylenic alcohols and ethers. 

Vinyl Halides. The Wittig reaction of bromomethylene triphenylphosphorane with aldehydes is an acceptable route to mainly (Z)-l-brome-alkenes if potassium t-butoxide is used as base to form the ylide. ° 2-Bromo-l-atkenes have been prepared by Markovnikov hydrobromination of 1-alkynes with tetraethylammonium hydrogen dibromide (Et4N HBr2)."°... 

This change caused considerable confusion in the early days of alkene chemistry, because one researcher would obtain only one hydrobromination product, whereas another would obtain a different product or mixtures from a seemingly identical reaction. The mystery was solved by Kharasch in the 1930s, when it was discovered that the culprits responsible for anti-Markovnikov additions were radicals formed from peroxides, ROOR, in alkene samples that had been stored in the presence of air. In practice, to effect anti-Markovnikov hydrobromination, radical initiators, such as peroxides, are added deliberately to the reaction mixture. 

Like alkenes, the double bonds of ,/3-unsaturated acids can be brominated, hydroxylated, hydrated, and hydrobrominated, although the reactions often are relatively slow. In the addition of unsymmetrical reagents the direction of addition is opposite to that observed for alkenes (anti-Markownikoff). Thus propenoic (acrylic) acid adds hydrogen bromide and water to form 3-bromo-and 3-hydroxypropanoic acids ... 

HBr, ROOR Hydrobromination Treatment with an alkene gives an awft-Maikovnikov addition of H and Br across the alkene. 

HBr, ROOR Hydrobromination When treated with HBr in the presence of peroxides, an alkene rmdergoes anf/-Markovnikov addition of H and Br. 

During the addition step, we must use a reaction that gives an awh-Maikovnikov addition (such as hydrobromination in the presence of peroxides). During the elimination step, we need the Hofmann product (less substituted alkene), so we use teri-butoxide as the base. The entire synthesis is shown here ... 

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