Phenols Markovnikov addition

The addition of hydrogen halides to simple olefins, in the absence of peroxides, takes place by an electrophilic mechanism, and the orientation is in accord with Markovnikov s rule.116 When peroxides are added, the addition of HBr occurs by a free-radical mechanism and the orientation is anti-Markovnikov (p. 751).137 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 HCI only rarely. In the rare cases where free-radical addition of HCI was noted, the orientation was still Markovnikov, presumably because the more stable product was formed.,3B Free-radical addition of HF, HI, and HCI is energetically unfavorable (see the discussions on pp. 683, 693). 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 (4-9). Markovnikov addition can be ensured by rigorous purification of the substrate, but in practice this is not easy to achieve, and it is more common to add inhibitors, e.g., phenols or quinones, which suppress the free-radical pathway. The presence of free-radical precursors such as peroxides does not inhibit the ionic mechanism, but the radical reaction, being a chain process, is much more rapid than the electrophilic reaction. In most cases it is possible to control the mechanism (and hence the orientation) by adding peroxides... 

Yasuda et al. have recently reported that irradiation of o-alkenylphenols and naphthols in the presence of primary or secondary amines results in Markovnikov addition of the amine. For example, irradiation of the alkenylphenol 12 with methyl-amine affords the adduct 13 (Scheme 4), The initial step in these reactions is proton transfer from the acidic phenol singlet state to the amine, which leads to the formation of the singlet phenolate anion and ammonium ion. Proton transfer from the ammonium ion to the phenolate anion yields a zwitterion, which undergoes nucleophilic addition of the amine. Thus the amine serves as a base in the initial step of this reaction and then as a nucleophile. 

Allyl p-tolyl sulphoxide 535 reacts with sodium methoxide in methanol by initial prototropic isomerization and subsequent addition of methanol to give 536 (equation 333). Protic solvents are photochemically incorporated by the open chain olefinic bond of trans methyl )S-styryl sulphoxide 537 in a Markovnikov regiospecificity (equation 334). Mercaptanes and thiophenols add to vinyl sulphoxides in a similar manner (compare also Reference 604 and Section IV.B.3) to give fi-alkylthio(arylthio)ethyl sulphoxides 538 (equation 335). Addition of deuteriated thio-phenol (PhSD) to optically active p-tolyl vinyl sulphoxide is accompanied by a low asymmetric a-induction not exceeding 10% (equation 336) . Addition of amines to vinyl sulphoxides proceeds in the same way giving )S-aminoethyl sulphoxides in good to quantitative yields depending on the substituents at the vinyl moiety When optically active p-tolyl vinyl sulphoxides are used in this reaction, diastereoisomeric mixtures are always formed and asymmetric induction at the p- and a-carbon atoms is 80 20 (R = H, R = Me) and 1.8 1 (R = Me, R = H), respectively (equation 337) ... 

The photoaddition of alcohols and phenols to alkenes has been observed.404 The equivalent intramolecular process results in cyclization and the formation of oxygen heterocycles. Irradiation of 2-allyl-4-(-butylphenol (388) affords 2,3-dihydro-2-methyl-5-<-butyl-benzofuran (389), whereas o-3-methylbut-2-enylphenol (390) gives 2,2-dimethylchroman (391). In both cases, therefore, the addition can be said to occur in a Markovnikov direction. 

Intermolecular Markovnikov-type addition of phenols (ArOH), carboxylic acids (RCO2H), and protected amines (TsNH2) to alkenes, such as 4-MeOC6H4CH2CH= CH2, can be catalysed by triflic acid in low concentrations (1-5%). Functional groups, such as the methoxyl on aromatics, can be tolerated if the concentration of triflic acid and the reaction temperature are controlled appropriately. This reaction provides one of the simplest alkene addition methods and can serve as an alternative to metal-catalysed reactions.33... 

PhsPAuOTf has been shown to catalyse the intermolecular addition of phenols and carboxylic acids to terminal alkenes, RCH2CH=CH2, at 85 °C in toluene with Markovnikov selectivity to produce RCH2CH(OR)Me.131 AUCI3 triggers the electrophilic 6(0)ir n-endo-dig cyclization of 2-(alk-l-ynyl)alk-2-en-l-ones to produce highly substituted furans in analogy with other electrophiles (see above Scheme 3).40... 

It is known that N-vinylindole [650-652] and N-vinylcarbazole [653-655], upon acid-catalyzed interaction with alcohols, give the corresponding N-(o-alkoxyethyl) derivatives (addition according to the Markovnikov rule). In the case of N-vinylindole, the HCl-catalyzed addition competes with the polymerization and considerably reduces the yields of adducts [650], N-Vinylpyrrolidone adds alcohols and phenols also according to the Markovnikov rule to afford N-[a-alk(ar)oxyethyl] pyrrolidones [647,656]. The benzene nucleus of phenols is reported to be alkylated by N-vinylpyrrolidone, the hydroxyl group remaining intact [647]. 

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