Markovnikov orientation rule

The 1,2-dipolar cycloaddition of chlorosulfonyl isocyanate to different cycloalkenes has become a well-known route for the synthesis of cycloalkane-fused p-lactams, and for alicyclic P-amino acids, after hydrochloric acid treatment. The addition takes places regio- and stereospecifically, in accordance with the Markovnikov orientation rule [51-55]. In this manner, a number of homologue and analogue alicyclic P amino acids have been prepared, such as czs-2-amino-2-methylcyclopentanecarboxylic acid [56], m-2-amino-2-methylcyclo-hexanecarboxylic acid [56], (l/ , 2S, 4S )2-amino-4-terMnitylcyclopenta-necarboxylic acid [55, 58], 3-exo-aminobicyclo[2.2.1]heptane-2-exo-carboxylic acid [59, 60] and 3-exo-aminobicyclo[2.2.1]hept-5-ene-2-exo-carboxylic acid [61]. 

Markovnikov s rule (Section 6.8) A guide for determining the regiochemistry (orientation) of electrophilic addition reactions. In the addition of HX to an alkene, the hydrogen atom bonds to the alkene carbon thal has fewer alkyl substituents. 

The addition of hydrogen halides to simple alkenes, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule. " When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 985). It must be emphasized that this is true only for HBr. Free-radical addition of HF and HI has never been observed, even in the presence of peroxides, and of HCl only rarely. In the rare cases where free-radieal addition of HCl was noted, the orientation was still Markovnikov, presumably beeause the more stable product was formed. Free-radical addition of HF, HI, and HCl is energetically unfavorable (see the discussions on pp. 900, 910). It has often been found that anti-Markovnikov addition of HBr takes place even when peroxides have not been added. This happens because the substrate alkenes absorb oxygen from the air, forming small amounts of peroxides... 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

The addition of a secondaiy amine (shown above) produces a tertiary amine, while addition of a primary amine gives a secondary amine. The overall orientation follows Markovnikov s rule. For conversion of 35 to other products, see 15-52. 

Electrophilic addition of HBr to propene gives predominantly the so-called Markovnikov orientation Markovnikov s rule states that addition of HX across a carbon-carbon multiple bond proceeds in such a way that the proton adds to the less-substituted carbon atom, i.e. that already bearing the greater number of hydrogen atoms (see Section 8.1.1). We rationalized this in terms of formation of the more favourable carbocation, which in the case of propene is the secondary carbocation rather than the alternative primary carbocation. 

Markovnikov s Rule A Russian chemist, Vladimir Markovnikov, first showed the orientation of addition of HBr to alkenes in 1869. Markovnikov stated ... 

This is the original statement of Markovnikov s rule. Reactions that follow this rule are said to follow Markovnikov orientation and give the Markovnikov product. We are often interested in adding electrophiles other than proton acids to the double bonds of alkenes. Markovnikov s rule can be extended to include a wide variety of other additions, based on the addition of the electrophile in such a way as to produce the most stable carbocation. 

Orientation of Halohydrin Formation Even though a halonium ion is involved, rather than a carbocation, the extended version of Markovnikov s rule applies to halohydrin formation. When propene reacts with chlorine water, the major product has the... 

An orientation of addition that obeys the original statement of Markovnikov s rule one that gives the Markovnikov product, (p. 333)... 

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. 334) (mefa-chloroperoxybenzoic acid) A common reagent for epoxidizing alkenes. MCPBA dissolves in common solvents such as dichloromethane. As the epoxidation takes place, the m-chlorobenzoic acid by-product precipitates out of solution, (p. 361)... 

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)... 

Hydrogen halides add across the triple bond of an alkyne in much the same way they add across the alkene double bond. The initial product is a vinyl halide. When a hydrogen halide adds to a terminal alkyne, the product has the orientation predicted by Markovnikov s rule. A second molecule of HX can add, usually with the same orientation as the first. 

Organic reactions are often written in different ways to emphasize different points.) 4. Orientation of addition Markovnikov s rule (Section 6.8). 

Strategy All of these reactions are electrophilic additions of HX to an alkene. Use Markovnikov s rule to predict orientation. 

Examination of a large number of such additions showed the Russian chemist Vladimir Markovnikov (of the University of Kazan) that where two isomeric products are possible, one product usually predominates. He pointed out in 1869 that the orientation of addition follows a pattern which we can summarize as In the ionic addition of an acid to the carbon-carbon double bond of an alkene the hydrogen of the acid attaches itself to the carbon atom that already holds the greater number of hydrogens. This statement is generally known as Markovnikov s rule. Thus Unto everyone that hath shall be given, or Them as has, gits. ... 

Addition of hydrogen halides to alkenes can be used to make alkyl halides. The fact that addition occurs with a specific orientation, as summarized by Markov-nikov s rule, rather than at random, is an advantage since a fairly pure product can generally be obtained. At the same time, the synthesis is, of course, limited to those products that are formed in agreement with Markovnikov s rule for example, we can make isopropyl iodide in this way, but not n-propyl iodide. (As we shall see later, there are other, more important ways to prepare alkyl halides.)... 

This reversal of the orientation of addition caused by the presence of peroxides is known as the peroxide effect. Of the reactions we are studying, only the addition of hydrogen bromide shows the peroxide effect. The presence or absence of peroxides has no effect on the orientation of addition of hydrogen chloride, hydrogen iodide, sulfuric acid, water, etc. As we shall see (Secs. 6.11 and 6.17), both Markovnikov s rule and the peroxide effect can readily be accounted for in ways that are quite consistent with the chemistry we have learned so far. 

---