Markownikov addition

As we have seen already (p. 104) secondary carbocations are more stable than primary, and in so far as this also applies to the transition states that precede them, (24) will be formed in preference to (23). In fact it appears to be formed exclusively, as the only addition product obtained is 2-bromopropane (25). Addition, as here, in which halogen (or the more negative moiety of any other unsymmetrical adduct) becomes attached to the more highly substituted of the two alkene carbon atoms is known as Markownikov addition. 

Other preparative snags also occur in the addition of HHal to alkenes. Thus in solution in H20, or in other hydroxylic solvents, acid-catalysed hydration (p. 187) or solvation may constitute a competing reaction while in less polar solvents radical formation may be encouraged, resulting in anti-Markownikov addition to give 1-bromopropane (MeCH2CH2Br), via the preferentially formed radical intermediate, MeCHCH2Br. This is discussed in detail below (p. 316). 

The diborane is generated (in situ, or separately, from NaBH4 and Et2Offi—BF3e), and probably complexes, as the monomeric BH3, with the ethereal solvent used for the reaction. BH3 is a Lewis acid and adds to the least substituted carbon atom of the alkene (Markownikov addition), overall addition is completed by hydride transfer to the adjacent, positively polarised carbon atom ... 

Addition to alkenes can be sensitized by both electron-donors and electron-acceptors, and it is most likely that the reactive species is the alkene radical anion or the alkene radical cation, respectively. 1,1-Diphenylethylene can be converted to the Markownikov addition product with methanol (2.48) using the electron-donating sensitizer t-methoxynaphthalene no added proton acid is needed. Using... 

The anti-Markownlkov orientation of addition in the presence of electron-acceptor sensitizers applies also to intramolecular reaction, and 5,5-dipheny pent-4-en-1-ol gives a tetrahydrofuran (2.SI) when irradiated in solution with 9,10-dicyanoanthracene, whereas its thermal reaction under proton-acid catalysis leads to 2,2-diphenyltetrahydropyran by Markownikov addition. Sometimes an added sensitizer is not required, if the alkene itself can act as a good electron-donor or electron-acceptor, and this is likely to be the reason why 1-lo-methoxyphenyl)propene adds photochemically to acetic acid (2.52), whereas l-phenylpropene does not. 

Anti-Markownikov addition may also result from steric hindrance Addition of iodine azide to the moderately hindered... 

The isomerization reaction of butene-1 has been carried out with D2SO4 in CH3OD [282). The product contained both deuterated and nondeuterated olefins in a ratio consistent with a random scrambling model. The initial step in the reaction involves an insertion of the olefin into the Ni—H bond to form an alkyl. Elimination from the alkyl obtained by Markownikov addition to the olefin can lead to isomerization, whereas elimination from the anti-Markownikov addition product leads to butene-1 being re-formed. The rate of isomerization to deuteration of the olefin is of the order of 170. 

Addition of carbon monoxide and water to an alkene, i.e. hydrocarboxylation, is catalyzed by a variety of transition metal complexes, including [Ni(CO)4], [Co2(CO)s] and [HaPtClg]. Unfortunately this reaction usually leads to mixtures of products due to both metal-catalyzed alkene isomerization and the occurrence of Irath Markownikov and anti-Markownikov addition of the metal hydride intermediate to the alkene. The commercially available zirconium hydride [(C5Hs)2Zr(H)Cl] can be used as a stoichiometric reagent for conversion of alkenes to carboxylic acids under mild conditions (equation 23). In this case the reaction with linear alkenes gives exclusively terminal alkyl complexes even if the alkene double bond is internal. Insertion of CO followed by oxidative hydrolysis then leads to linear carboxylic acids in very good yield. 

The Markownikov addition of the elements of water to a cleavamine derivative may also have important application in the synthesis of bisindole alkaloids. Although this appears not to have been achieved, a route to the corresponding derivative of catharanthine has been developed, by use of a modified Prevost reaction. Thus, treatment of catharanthine with iodine and silver acetate in glacial acetic acid afforded an intermediate, which was reduced to the acetate (223) by NaBH4. Although formulated otherwise this acetate must be the 20a -acetate, by reason of its later conversion into vinblastine (q.v.). 

HCN also adds to alkenes in the presence of an appropriate catalyst (Arthur et al., 1954 Jackson and Level, 1982). Thus, cobalt carbonyl leads to Markownikov addition, for example, 1-propene yields isopropyl cyanide in approximately 75% yield. HCN adds to alkynes in the presence of metal complexes, and the use of a nickel complex may lead to syn addition (Jackson and Level, 1983 Jackson et al., 1988). Hydrogen cyanide reacts with conjugated dienes, the mechanism involving a TT-allyl intermediate. The course of addition is complex and may lead to more than one product (Keim et al., 1982). 

Markownikov addition of HQ to the 6,7-double bond (82.206). The resulting chlorolactams possess the same ring system as leuconoxine (74), from Leuconotis eugemfoUus. The structure of275was confirmed by X-ray crystal structure determination (207). A second reaction of considerable interest is that of leuconolam with potassium hydroxide in methanol, which involves the removal of a proton from C-16, followed by internal Michael addition to the 6,7-double bond. The product is the pentacyclic dilactam 277, which contains the meloscine ring system (82). 

A new enzymatic process in which penicillin-G acylase from E. coli, catalyzes the Markownikov addition of l,5-dihydro-pyrazolo[3,4-(/]pyrimidin-4-one 89 to vinyl ester 90 to obtain pyrazolopyrimidine 91 has been reported <05CC2348>. 

A study of the photohydration of the alkynes 11 and 12 in sulphuric acid has shown that only the normal Markownikov products, in this instance in the keto form 13, are formed. The mechanism, as proposed by Yates and collaborators involves a rate-limiting protonation of the Si state of the alkyne. This leads to the cation 14, solvation of which affords the enol of the final product. Associated with this, and providing spectroscopic substantiation, is the report of the direct observation of the enol of acetophenone during a study of the photohydration of phenylacetylene The introduction of nitro substituents as in 15 leads to abnormal Markownikov addition products. Excitation in these systems results in a reversal of polarity in the excited state, consistent with the... 

Relative rates of anti-Markownikov addition and Markownikov addition, i.e. < (,.roi.an-i oiiM(i.rt)i.an a.oi)-10 A quoted in units of l.mole .atm. min referring to gaseous rather than dissolved olefin. 

The reverse reaction will be discussed in section 8.3. An a-carbon of vinyli-dene ligand, generated from 1,2-hydrogen shift of terminal alkyne upon contact with coordinatively unsaturated metal fragment, is also susceptible to the nucleophilic attack (Scheme 8.17). This attack is believed to constitute a catalytic cycle for anti-Markownikov addition of NuH (Nu = RO, RCOO, etc.) to alkynes [4c]. Schrock carbenes are sensitive to electrophiles (see 8.3.1), but not to nucleophiles. 

Further studies of carbene insertion into the C S bond are reported, the authors earlier work on alkyl allyl sulphides, using bis(methoxy-carbonyl)carbene, now being supplemented by a study of the relative tendencies towards C—S insertion and C=C addition for the same substrates with carbethoxycarbene (from ethyl diazoacetate). 1,2-Diphenyl-ethyl phenyl sulphide, PhCH(CHaPh)SPh, is formed by the action of benzyne on dibenzyl sulphide, via the sulphonium ylide. Alkylation at sulphur is one of the best-known reactions of sulphides, and novel syntheses of this type have been reported in which the formation of hydro-quinone sulphonium salts, from quinone and a sulphide in 70% H2SO4 at — 5 to -f 5 and Markownikov addition of a sulphide to an alkene under similar conditions are discussed. 

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