Addition, Markownikoff

Acid-Gatalyzed Synthesis. The acid-catalysed reaction of alkenes with hydrogen sulfide to prepare thiols can be accompHshed using a strong acid (sulfuric or phosphoric acid) catalyst. Thiols can also be prepared continuously over a variety of soHd acid catalysts, such as seoHtes, sulfonic acid-containing resin catalysts, or aluminas (22). The continuous process is utilised commercially to manufacture the more important thiols (23,24). The acid-catalysed reaction is commonly classed as a Markownikoff addition. Examples of two important industrial processes are 2-methyl-2-propanethiol and 2-propanethiol, given in equations 1 and 2, respectively. 

Free-Radical-Initiated Synthesis. Free-radical-initiated reactions of hydrogen sulfide to alkenes are commonly utilized to prepare primary thiols. These reactions, where uv light is used to initiate the formation of hydrosulfuryl (HS) radicals, are utilized to prepare thousands of metric tons of thiols per year. The same reaction can be performed using a radical initiator, but is not as readily controlled as the uv-initiated reaction. These types of reactions are considered to be anti-Markownikoff addition reactions. 

The main by-products of this synthesis type are sulfides and the isomer resulting from the Markownikoff addition to the alkene. For example, in the synthesis of 1-butanethiol (eq. 4), 5-thianonane, C H SC H, and 2-butanethiol are produced as by-products. The 2-butanethiol has uses as a herbicide intermediate and a gas odorant blend component and is further processed. The 5-thianonane is incinerated or reprocessed for fuel value. Sulfides account for up to 10% of the thiols produced. Another 2—5% is the Markownikoff addition product. 

The regioselectivity of addition of Itydrogen bromide to alkenes can be complicated if a free-radical chain addition occurs in competition with the ionic addition. The free-radical reaction is readily initiated by peroxidic impurities or by light and leads to the anti-Markownikoff addition product. The mechanism of this reaction will be considered more fully in Chapter 12. Conditions that minimize the competing radical addition include use of high-purity alkene and solvent, exclusion of light, and addition of free-radical inhibitors. ... 

The anti-Markownikoff addition of hydrogen bromide 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 hydrogen bromide ... 

The overall result of the sequence hydroboration -I- oxidation is a regioselective and-Markownikoff-addition of water to an alkene. This reaction is an important method in organic synthesis, since it can be made stereoselective and even enantioselective. 

The hydroboration of olefins at about room temperature leads to trialkylboranes by anti-Markownikoff addition 20) ... 

Essentially the same sequence of reactions was proposed (22a) to explain the isomerization of olefins which accompanies the stoichiometric hydroformylation of olefins. In particular, it has been suggested that the active catalyst is cobalt hydrotricarbonyl, which first adds by Markownikoff addition and is then eliminated in the opposite direction ... 

Ordinarily, DCo(CO)4 would be expected to add to an olefin to an appreciable extent by anti-Markownikoff addition, since with olefins more straight chain than branched chain product results. Such addition would place deuterium on the penultimate carbon atom. It can be argued that allyl alcohol is not an olefin and therefore might be expected to behave differently. As usual more work is necessary. A similar isomerization of allyl alcohol to propanal using FelCO) has been reported by Emerson and Pettit (24). 

The result is a cis, anti-Markownikoff addition of water. The C-B bond is converted into a C-OH bond with retention of stereochemistry. 

Selectivity. The insertion of the coordinated 1-alkene creating an alkyl intermediate may proceed either by Markownikoff or anti-Mark-ownikoff addition, but only Markownikoff addition can lead to isomerization. A mechanism which describes both hydrogenation and isomerization may thus be expressed ... 

The addition of HX to double bonds in the dark and in the absence of free-radical initiators is closely related to hydration The orientation of the elements of HX in the adduct always rnrrrsponds to Markownikoff addition 16 no deuterium exchange wish solvent is found in unreacted olefins recovered after partial reaction, nor is recovered starting material isomerized after partial reaction.17 However. the addition of HX apparently can proceed by a number of different mechanisms depending on the nature Ol the substrate and on the reaction conditions. Thus when HC1 is added to f-butylethylene in acetic acid, the rate is first-order in each reactant and the products are those shown in Equation 7.5.le Since 4 and 6 were demonstrated to be stable to the reaction conditions, the rearranged product (5) can be formed only if a carbocationic intermediate is formed during reaction. However, the carbocation exists almost solely in an intimate ion pair, and the rate of collapse of the ion pair to products must be faster than, or comparable to, the rate of diffusion of Cl- away from the carbocation. This must be so because the ratio of chloride to acetate products is unaffected by... 

Another piece of evidence for the bromonium ion is that addition is less regiospecific when bromine is the electrophile then when HaO+ attacks. With molecular bromine we cannot, of course, observe the site at which the original electrophilic bromine attacks, but with unsymmetrical reactants such as HOBr or BrCl we can. Thus, for example, the addition of BrCl to propene in aqueous HC1 gives only 54 percent of the Markownikoff addition product (26) and 46 percent of the anti-Markownikoff product (27). 40 The chloride ion apparently has the... 

Thus hydroboration of a double bond followed by peroxide oxidation is a convenient procedure for converting the olefin into the alcohol corresponding to anti-Markownikoff addition of water. 

Nitric oxide as a reagent gas for the Cl has been proposed by Hunt and Harvey111. The ions mlz 30 (NO+) and m/z 60 ([NO NO]+) react with internal olefins and dienes to produce (M + NO)+, M+ and (M — 1)+. Terminal olefins produce in addition a series of fragments derived from the Markownikoff addition of NO+ to the olefin linkage. This... 

Addition to double bonds. Alkenes react with TeCl to give mainly products of svn-addition of Cl and TeCl,. Only Markownikoff addition occurs with terminal alkenes. The reaction with allylic esters is unusual it involves. svn-1.3-addition with a 1,2-rear-... 

The efficiency of nucleophilic addition of methanol to the radical cation of arylalkenes can be improved by use of a redox sensitizer system, and also by utilizing solvent and additive effects. Pac and his coworkers found that the aromatic hydrocarbon-electron acceptor sensitizer system, such as phenan-threne-p-dicyanobenzene system, acts as an excellent redox sensitizer for the anti-Markownikoff addition of methanol to 1,1-diphenylethene and indene (Scheme 7) [29]. 

Hydroboration. When these two reagents are mixed in THF, hydrogen is evolved and a solution of a violet titanium-boron complex forms. This complex catalyzes the hydroboration of alkenes with LiBH4 to form lithium alkylboro-hydrides, which are converted to alcohols by NaOCHj and H2O2. The relative reactivity of alkenes is terminal > cyclic > internal. The reaction involves anti-Markownikoff addition. 

Cyclic nitro olefins. Some years ago Bachman and Whitehouse reported the Markownikoff addition of mercury(II) nitrite to olefins. The salt is generated in situ from mercury(II) chloride and sodium nitrite. Because of the requirement for an aqueous medium the rate is slow the reaction is also subject to steric effects. 

The classical examples of electrophilic addition are those of the addition of the hydrogen halides and are exemplified by the addition of hydrogen chloride under ionic conditions, when the products are those of Markownikoff addition (Scheme 3.5). 

AtUUtiou of bromine fluoride to acetylenes. Bromine fluoride reacts with terminal alkynes by Markownikoff addition ... 

A number of the photoaddition reactions of alkynes are not reactions of the alkyne excited state but involve the formation of free radicals by photocleavage of the other compound. The photochemical a/i//-Markownikoff addition of hydrogen bromide to alkynes (equation 35) under conditions where the ionic addition is very slow is an example of this -. 

Cases exist where steric factors counteract these general polar directive effects (Table 8, compounds 214-219). For example, whereas polar effects direct the addition in compounds 214 and 215, for 3,3-dimethylbut-l-ene (216) adverse steric interactions between the approaching azide ion and the i-butyl group preclude the electronically controlled ring opening of the iodonium ion. Instead, anti-Markownikoff addition occurs with the formation of l-azido-2-... 

Hydrogen sulfide is a better nucleophile than water and will undergo nucleophilic addition to alkenes and alkynes in the presence of an acidic catalyst, e.g. sulfuric acid or aluminium chloride (Markownikoff addition). The reaction goes well with suitable alkenes and provides a preparative route to thiols (Scheme 9). 

Alkane-and arenesulfenyl chlorides add to alkenes and alkynes thus, the addition of 2,4-dinitrobezenesulfenyl chloride (61) may be used to prepare solid derivatives of alkenes, e.g. the adduct (62) (Scheme 37). The Markownikoff addition of a sulfenyl chloride to an alkene is stereospecifically trans the adduct may be sequentially treated with a Lewis acid and a nucleophilic reagent to achieve the introduction of a new carbon-carbon bond (64) via the episulfenium ion intermediate (63) (Scheme 38). The procedure can also be applied to the synthesis of unsaturated sulfides, e.g. (65) (Scheme 39). 

Reduction of (1) with DIBAH in THF leads mainly to the homoallylic alcohol (4) formed by direct, Markownikoff addition of the hydride to the epoxide. Reduction of (1) with lithium aluminum hydride gives exclusively the tertiary allylic alcohol (5). 

Counter-Markownikoff addition of HBr, Kharasch and Mayo discovered that, in the presence of dibenzoyl peroxide, hydrogen bromide adds to unsymmetrical olefins in the counter-Markownikoff direction. 

Bromohydrins. Dalton et al. have prepared bromohydrins by reaction of olefins with NBS in aqueous DMSO. The reaction involves stereospecific Markownikoff addition thus trans-1 -phenyl-1 -propene is converted into erythro-2-bromo-1 -phenylpropanol in 92% yield. The exact nature of the reagent is not... 

The procedure has been applied to unsaturated alcohols if the hydroxyl group is capable of participation to form a tetrahydrofurane or tetrahydropyrane, these cyclic ethers are formed in good yield. Otherwise the expected diols are obtained. The procedure is also applicable to non-conjugated and conjugated dienes. In each case diols are obtained in good yield and the structures are consistent with two consecutive 1,2-Markownikoff additions.2... 

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