Anti-Markownikoff addition

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

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. 

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. 

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. 

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-... 

Furthermore, vinylsilanes are a reality and undergo an anti-Markownikoff addition of HBr as a result of the (p-d)ir bond influence, Equation 6. 

With alkenes other than ethylene, there is, of course, the possibility of addition of M—H to the double bond in either the MarkownikoflF or the anti-Markownikoff direction, just as with the addition, say, of hydrogen chloride. Thus we may have reactions that give either product (A) or product (B). Since in the anti-Markownikoff addition the H atom is transferred from... 

The high PPh3 concentrations that are essential to provide high yields (>95%) of linear aldehyde are probably required in order to suppress dissociation and the formation of monophosphine species, and also to force the associative attack of olefin on the bisphosphine species (A), for which the specificity of anti-Markownikoff addition is high. 

Hydroboration-oxidation gives anti-Markownikoff addition of water across the carbon-carbon double bond. 

AlkyWthium reagents. 1-Alkenes can be converted into these reagents in two steps anti-Markownikoff addition of thiophenol followed by cleavage of the resulting alkyl phenyl sulfides with a form of lithium metal (equation I). The... 

The activation energies for PH3 addition to alkenes were calculated by a simple electrostatic model of point dipoles. Anti-Markownikoff addition was found always to require a higher activation energy than the normal Markownikoff addition [29]. 

Since the bromine adds to the least-substituted carbon atom of the bond, thus generating the more-substituted radical intermediate, the regiospecificity of radical-chain hydrobromination of olefins is opposite that of ionic addition. The early work on the mechanism of the reaction was undertaken to understand why Markow-nikoff s rule was violated under certain circumstances. Anti-Markownikoff additions were eventually traced to reaction conditions under which peroxides or light were causing initiation of the radical-chain process. The radical chain addition of hydrogen bromide to olefins is a synthetically useful reaction, as illustrated by entries 1 and 2 in Scheme 12.4. 

The five-membered ring products result from the normal (Markownikoff) internal addition of the thiol group to the double bond, whereas the six-membered ring products result from abnormal (anti-Markownikoff) addition, which is characteristic of a free radical process. The formation of both heterocycles thus indicates competitive thermally induced heterolytic and homolytic fissions of the thiol S—H bond (equation 7). The cyclization mechanisms were verified by a detailed examination of the thermal behaviour of 104. Product 102 was formed almost exclusively... 

Sulphides are formed when a thiol adds onto an olehnic bond. Most of the reactions reported correspond to anti-Markownikoff addition, but this is probably a free radical mechanism, which also occurs in the presence of minute traces of peroxides. With carefully purified reagents in the presence of acid, Markownikoff addition occurs ... 

The addition of thiols to olefins, giving molecules with thioether or monosulfide linkages, is well documented. In the presence of peroxides or UV light, the reaction gives anti-Markownikoff addition products. Using dithiols and diolefins, a wide variety of polythioethers have been prepared and evaluated. 

The ready availability of the pinenes makes them attractive potential feedstocks for /-menthol production. A number of routes have been published, but the only commercially successfiil one is that described above, which uses myrcene as an intermediate. One alternative approach is as shown in Fig. 8.41 using citronellene, prepared from (—)-P-pinene, as a key intermediate. The difficult step is to convert the citronellene to citronellol and two ways of achieving this are shown. The first uses an aluminium alkyl as described above under citronellene and citronellol. The second uses hydrochlorination of the trisubstituted double bond followed by anti-Markownikoff addition of hydrogen bromide to the other, then selective solvolysis and elimination. A process along these lines was developed by GUdden in the 1960s [206, 230], but was never commercialized. 

Table 6 shows how the addition of thioxanthene influences the oligomerization of ethylene with the system TiCl4/C2H5AlCl2 in 1,2-dichloroethane. The incorporation of a-olefins is reduced, as shown by the decreased number of branches per molecule as well as by the distribution of double bonds. The most striking feature is perhaps the drastic diminution the inner double bonds. Whereas in the absence of thioxanthene there is a clear tendency to the anti-Markownikoff addition of a-olefin (see also Table 2), the appearance of vinylidene end-groups in the presence of the sulfur compound indicates that, if a-olefins... 

Butadiene allowed to react at 0° with phenol in the presence of i r-allylpalladium chloride and Na-phenoxide, then triphenijlphosphine added to the mixture containing l-phenoxyocta-2,7-diene, and distilled under reduced pressure 1,3,7-octatriene. Y 85% purity 98%. - This is a convenient prepn. of a hitherto inaccessible butadiene dimer. Also isolation of the intermediate, use of other Pd-catalysts such as Pd-chloride, and f. anti-Markownikoff additions of nucleophiles to the linear butadiene dimer s. E. J. Smutny, Am. Soc. 89, 6793 (1967) cf. S. Takahashi et al.. Bull. Ghem. Soc. Japan Al, 254, 454 (1968). 

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