Addition anti-Markovnikov orientation

Free-radical addition Anti-Markovnikov orientation... 

Organoboranes react with a mixture of aqueous NH3 and NaOCl to produce primary amines. It is likely that the actual reagent is chloramine NH2CI. Chloramine itself,hydroxylamine-O-sulfonic acid in diglyme, and trimethyl-silyl azide " also give the reaction. Since the boranes can be prepared by the hydroboration of alkenes (15-16), this is an indirect method for the addition of NH3 to a double bond with anti-Markovnikov orientation. Secondary amines can be prepared by the treatment of alkyl- or aryldichloroboranes or dialkylchlorobor-anes with alkyl or aryl azides. 

Compared to a bromonium ion, the C-S bonds are stronger and the TS for nucleophilic addition is reached later. This is especially true for the sulfurane structures. Steric interactions that influence access by the nucleophile are a more important factor in determining the direction of addition. For reactions involving phenylsulfenyl chloride or methylsulfenyl chloride, the intermediate is a fairly stable species and ease of approach by the nucleophile is the major factor in determining the direction of ring opening. In these cases, the product has the anti-Markovnikov orientation.62... 

Both electronic and steric factors accounts for the anti-Markovnikov orientation of the addition. 

Now, just the same sort of rationalization can be applied to the radical addition, in that the more favourable secondary radical is predominantly produced. This, in turn, leads to addition of HBr in what is the anti-Markovnikov orientation. The apparent difference is because the electrophile in the ionic mechanism is a proton, and bromide then quenches the resultant cation. In the radical reaction, the attacking species is a bromine atom, and a hydrogen atom is then used to quench the radical. This is effectively a reverse sequence for the addition process but, nevertheless, the stability of the intermediate carbocation or radical is the defining feature. The terminologies Markovnikov or anti-Markovnikov orientation may be confusing and difficult to remember consider the mechanism and it all makes sense. 

Water can be added indirectly, with anti-Markovnikov orientation, by treatment of the alkene with a 1 1 mixture of PhCH2NEt3+ BH4 and Me3SiCl, followed by addition of an aqueous solution of K2C03.152 For another method of anti-Markovnikov hydration, see 5-12. With substrates of the type C=C—Z (Z is as defined on p. 741) the product is almost always HO—C—CH—Z and the mechanism is usually nucleophilic,153 though electrophilic... 

Radical Addition of HBr to Unsymmetrical Alkenes Now we must explain the anti-Markovnikov orientation found in the products of the peroxide-catalyzed reaction. With an unsymmetrical alkene like 2-methylbut-2-ene, adding the bromine radical to the secondary end of the double bond forms a tertiary radical. 

The boron atom is removed by oxidation, using aqueous sodium hydroxide and hydrogen peroxide (HOOH or H2C>2) to replace the boron atom with a hydroxyl (—OH) group. The oxidation does not affect the orientation of the product, because the anti-Markovnikov orientation was established in the first step, the addition of BH3. 

A reaction in which one direction of bond making or bond breaking occurs preferentially over all other directions. For example, the addition of HC1 is regioselective, predicted by Markovnikov s rule. Hydroboration-oxidation is regioselective because it consistently gives anti-Markovnikov orientation, (p. 332)... 

In Section 8-3B, we saw the effect of peroxides on the addition of HBr to alkenes. Peroxides catalyze a free-radical chain reaction that adds HBr across the double bond of an alkene in the anti-Markovnikov sense. A similar reaction occurs with alkynes, with HBr adding with anti-Markovnikov orientation. 

Hydroboration-Oxidation In Section 8-7 we saw that hydroboration-oxidation adds water across the double bonds of alkenes with anti-Markovnikov orientation. A similar reaction takes place with alkynes, except that a hindered dialkylborane must be used to prevent addition of two molecules of borane across the triple bond. Di(second-ary isoamyl)borane, called disiamylborane, adds to the triple bond only once to give a vinylborane. (Amyl is an older common name for pentyl.) In a terminal alkyne, the boron atom bonds to the terminal carbon atom. 

The best experimental conditions to introduce a phenylseleno and an azido group to the alkene double bond are those which employ diphenyl diselenide, sodium azide and iodobenzene diacetate in methylene chloride. Under these conditions, however, the addition reaction occurs through the radical mechanism illustrated in Scheme 12 [581. The addition therefore occurs with an anti Markovnikov orientation and it is not stereospecific. The reaction is initiated by the oxidation of the azido anion to the azido radical, which adds to the alkene to afford a carbon radical. This is trapped by the PhSeSePh to afford the final product and a PhSe radical, which dimerizes to give the diselenide. 

The 2° radical is more stable than 1°. The anti-Markovnikov orientation occurs because the bromine radical attacks first to make the most stable radical, which is contrary to electrophilic addition where the Ff attacks first (see the solution to 9-15). 

The reaction with HBr is also significant in terms of regiochemistry. The reaction results in the anti-Markovnikov orientation, with the bromine adding to the less-substituted carbon of the double bond. The anti-Markovnikov addition of HBr to alkenes was one of the earliest free radical reactions to be put on a firm mechanistic basis. In the presence of a suitable initiator, such as a peroxide, a radical chain mechanism becomes competitive with the ionic mechanism for addition of HBr. 

This reaction (termed hydroboration-oxidation) is an excellent method of making alcohols of anti-Markovnikov orientation. The addition of water to the carbon-carbon double bond in anti-Markovnikov fashion probably occurs because the boron group attaches first to the terminal doubly bonded carbon to give the most stable transition state. However, no carbonium ion is formed in this reaction,... 

In each case, the reaction proceeds with syn-addition (hydration) and anti-Markovnikov orientation. 

Markovnikov orientation An orientation of addition that obeys the original statement of Markovnikov s rule one that gives the Markovnikov product, (p. 325) anti-Markovnikov orientation An orientation of addition that is the opposite of that predicted by the original statement of Markovnikov s rule one that gives the anti-Markovnikov product, (p. 326)... 

The hydroboration-oxidation procedure is a valuable method to hydrate an alkene with anti-Markovnikov orientation and with syn addition of the H and OH groups. ° Addition of BH3 (which may be added to the reaction mixture as diborane, B2Hg) to an alkene occurs readily in diethyl ether, THF, or similar solvent. The hydroboration is strongly exothermic, with a AH of -33kcal/mol per B-H bond that reacts. If stoichiometry and the steric requirements of the alkyl substituents on the boron atom permit, the reaction proceeds until three alkyl groups are attached to each boron atom. The trialkylborane can then be oxidized with hydrogen peroxide in aqueous base to produce the alcohol. 

We can add HBr in an anti-Markovnikov orientation (Section 10.9), by treating an alkene with HBr and a peroxide. (The other hydrogen halides do not undergo anti-Markovnikov addition when peroxides are present.)... 

Electrophilic addition of HCl or HBr to an alkene normally occurs with Mar-kovnikov regiochemistry, resulting in an alkyl halide with the halogen located at the more substituted carbon of the starting alkene. Since the presence of peroxides (ROOR) initiates a radical mechanism, HBr can also be added to an alkene with anti-Markovnikov orientation. Anti addition of bromine or chlorine to an alkene gives a trans-dibromo or dichloro product. 

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