MARKOVNIKOV Regio selectivity

Section 6.8 Hydrogen bromide is unique among the hydrogen halides in that it can add to alkenes either by electrophilic or free-radical addition. Under photochemical conditions or in the presence of peroxides, free-radical addition is observed, and HBr adds to the double bond with a regio-selectivity opposite to that of Markovnikov s rule. 

Regio-selective addition to alkenes The Markovnikov s rule... 

The mechanistic complexity of hydroboration-oxidation stands in contrast to the simplicity with which these reactions are carried out experimentally. Both the hydrobo-ration and oxidation steps are extremely rapid reactions and are performed at room temperature with conventional laboratory equipment. Ease of operation, along with the fact that hydroboration-oxidation leads to syn hydration of alkenes and occurs with a regio-selectivity opposite to Markovnikov s rule, makes this procedure one of great value to the synthetic chemist. 

The electron-rich alkene double bond reacts with a proton so as to make the most stable intermediate carbocation. The addition is regio-selective, and the so-called Markovnikov (also spelt Markownikoff) product is formed. If a peroxide is added, the reaction proceeds via radical intermediates to give the anti-Markovnikov product. 

Nickel(0) catalysts have featured prominently in this field with tetrakis(tri- -tolyl phosphite)nickel(O) allowing regio-selective Markovnikov addition of hydrogen cyanide to olefins at temperatures above 50°C. Interestingly, addition of Lewis acid hydrocyanation promoters reduced the selectivity of the reaction. 

The Markovnikov regioselectivity of the gem-alkenes is associated with a chemoselectivity. in favour of methanol attack, significantly greater than that observed for the other alkenes. If no sodium bromide is added to the reaction medium, no dibromide is observed for this series. Therefore, these alkenes behave as highly conjugated olefins, as regards their regio- and chemo-selectivity. In other words, the bromination intermediates of gem-alkenes resemble P-bromocarbocations, rather than bromonium ions. Theoretical calculations (ref. 8) but not kinetic data (ref. 14) support this conclusion. 

Addition takes place selectively when the reaction is carried out in methanol by using the redox couple of Br /Br+ as the mediator as shown by some typical examples in Table 36. The mechanism of this 1,2-addition may be as shown in equation 3 on the basis that it is regio- and stereoselective and follows the Markovnikov rule. 

Success was obtained with Ru3(CO)i2 as catalyst precursor [6], but the most efficient catalysts were found in the RuCl2(arene)(phosphine) series. These complexes are known to produce ruthenium vinylidene spedes upon reaction with terminal alkynes under stoichiometric conditions, and thus are able to generate potential catalysts active for anti-Markovnikov addition [7]. Similar results were obtained by using Ru(r]" -cyclooctadiene)(ri -cyclooctatriene)/PR3 as catalyst precursor [8]. (Z)-Dienylcarba-mates were also regio- and stereo-selectively prepared from conjugated enynes and secondary aliphatic amines (diethylamine, piperidine, morpholine, pyrrolidine) but, in this case, RuCl2(arene) (phosphine) complexes were not very efficient and the best catalyst precursor was Ru(methallyl)2(diphenylphosphinoethane) [9] (Scheme 10.1). 

Although Markovnikov addition is generally observed, little woik on the regio- or stereo-selectivity of this reaction has been reported. Both cis- and franr-2-pentene afford mixtures of the 2- and 3-substituted amines.199 a.p-Unsaturated esters yield 3-amino esters.200 The aminomercuration of cis- and trans-2-butenes gives S 97% of the anti adducts.201... 

Caesium fluoroxysulphate has been reported to add to alkenes (1-hexene, styrene, cyclohexene and others), furnishing vicinal fluorosulphates. The regio- and stereo-selectivity is rather low and may be partially influenced by the solvent some preference for anti-Markovnikov products and for syw-addition has been observed. The slight predominance of cA-products seems to be consistent with a concerted mechanism173. 

Kinetic analysis of the reaction between 60 and 110°C yields = +9.1(0.7) kcal/mol and AS - —45(2) eu, suggesting a highly ordered transition state and an intermolecular, turnover-limiting step. The hydrothiolation processes exhibits a high Markovnikov selectivity. This is presumably reflecting a four-membered transition state with the alkyne insertion regio-chemistry dictated by the transition state steric hindrance and the bond polarity orientation. 

The great application of boranes in organic synthesis is the regio- and stereoselective hydroboration cis addition) of terminal alkenes (anti-Markovnikov) that is selective when the R groups are large enough. Boranes currently used are disiamyl-borane and 9-BBN. - ... 

A variety of alkynes undergo regio- and stereoselective hydrothiolation with arenethiols in the presence of RhCl(PPh3)3. Ethanol and dichlorometane is suitable solvents for this hydrothiolation. This hydrothiolation proceeds well, even when galvinoxyl as a radical inhibitor is added to the reaction system. Recently, Wilkinson s catalyst is reported to be an excellent catalyst for alkyne hydrothiolation with alkanethiols to provide -isomers of anri-Markovnikov-type addition products 3 selectively [54]. 

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