Markownikoff hydration

Aminophenols from anilines, 35, 2 Anhydrides of aliphatic dibasic acids, Friedel-Crafts reaction with, 5, 5 Anion-assisted sigmatropic rearrangements, 43, 2 Anthracene homologs, synthesis of, 1, 6 Anti-Markownikoff hydration of alkenes, 13, 1... 

The direction of addition of the B-H bond to atrisubstituted double bond seems to be determined by the addition of the more electronegative hydrogen atom to the more highly substituted carbon atom of the double bond. Thus, with the B H bond assumed to be polarised in the sense B " —the process may be considered in terms of the electronic arguments summarised in the modern interpretation of Markownikoff s rule for ionic additions to double bonds [15]. The outcome of the hydroboration/oxidation sequence corresponds to an "anti-Markownikoff hydration of the double bond, which has many synthetic applications. If steric factors are also important, these of course operate in the same sense, generally favouring attachment of boron to the less-hindered secondary carbon atom. 

An alternative sequence involves the hydroboration of an alkene (Scheme 2.10c). This reaction has the overall effect of producing the anti-Markownikoff hydration of the double bond. A further characteristic of this pathway is that there is a cis relationship between the added hydrogen derived from the borane and the hydroxyl group. 

The synthetic value of the reaction lies in the modification of these organoboranes. The commonest reaction involves the decomposition of the borane by alkaline hydrogen peroxide. The highly nucleophilic hydroperoxide anion attacks the electron-deficient boron with the formation of an ate complex. Rearrangement of this leads to the formation of a borate ester which then undergoes hydrolysis to an alcohol in which an oxygen atom has replaced the boron (Scheme 3.15). The overall outcome of this reaction is the anti-Markownikoff hydration of the double bond. The regiochemistry is the reverse of the acid-catalysed hydration of an alkene. The overall addition of water takes place in a cis manner on the less-hindered face of the double bond. 

Markownikoff hydration of olefins (2, 265-267). Brown and Geoghegan1 have reported a detailed study of the oxymercuration-demercuration procedure. Yields of alcohols in the case of terminal olefins, RCH=CH2 and R2C=CH2, and disubstituted internal olefins, RCH=CHR are practically quantitative. Tri-substituted olefins of the type R2C=CHR show a wide variation in reactivity. 1 -Phenylcyclopentene and 1 -phenylcy clohexene, for example, are unreacti ve. 

The tri-2-phenylpropylborane formed can be oxidized and hydrolyzed to 2-phenylpropanol-l, thus representing [as with aluminum alkyls (146)] an overall anti-Markownikoff hydration of a-olefins. Besides employing trialkylboranes as a source of boron hydrides, similar additions have been accomplished by heating olefins with boron hydride-amine complexes. As the latter are not as oxygen-sensitive, they are easier to handle (73) ... 

The anfi-Markownikoff-hydration of carbon-carbon double bonds hydroboration-oxidation has been supplemented by a remarkably simple and likewise stereospecific Markownikoff-hydration achieved by a one-step oxymercuration-demercuration p-Nitrophenyl chloroformate has been recommended for the protection of hydroxyl groups in nucleosides... 

A mixture of d- and l- hexoses also results from the hydroboration of these 5-enes. Hydroboration results in anti-Markownikoff, cw-hydration of the double bond and the amount of each hexose formed varies according to the nature of the substituent groups. For example, hydroboration (23) of methyl 6-deoxy-a-D-ryZo-hex-5-enopyranose (3) affords methyl a-D-glucopyranoside and methyl / -L-idopyranoside in the ratio of 1 2.5 respectively whereas hydroboration of the fris-trimethylsilyl ether of 3 afforded them in the ratio 1 0.6 respectively. The hydroboration method can be used to achieve specific labelling of hexoses with tritium methyl-/ -L-idopyranoside[5-H3] and methyl a-D-glucopyranoside [5-H3] were thus prepared (23). Similarly, hydroboration of the D-Zt/ro-hex-5-eno derivative (14) with diborane-H3 followed by removal of the isopropyli-dene group, afforded methyl a-D-mannopyranoside [5-H3] and methyl / -L-gulopyranoside [5-H3] in the ratio of 1 2 respectively (23). 

The most synthetically valuable method for converting alkynes to ketones is by mercuric ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markownikoff rule. Internal alkynes will give mixtures of ketones unless some structural feature promotes regioselectivity. Reactions with Hg(OAc)2 in other nucleophilic solvents such as acetic acid or methanol proceed to / -acetoxy- or /i-mcthoxyalk-enylmercury intermediates.116 These intermediates can be reduced to alkenyl acetates or solvolyzed to ketones. The regiochemistry is indicative of a mercurinium ion intermediate which is opened by nucleophilic attack at the more positive carbon that is, the additions follow the Markownikoff rule. Scheme 4.7 gives some examples of alkyne addition reactions. 

The R—0—B bonds are hydrolysed in the alkaline aqueous solution, generating the alcohol. The oxidation mechanism involves a series of B-to-0 migrations of the alkyl groups. The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with the stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least substituted carbon of a double bond results in the alcohol being formed with regiochemistry which is complementary to that observed in the case of direct hydration or oxymercuration, that is, anti-Markownikoff. 138... 

Like alkenes, the double bonds of ,/3-unsaturated acids can be brominated, hydroxylated, hydrated, and hydrobrominated, although the reactions often are relatively slow. In the addition of unsymmetrical reagents the direction of addition is opposite to that observed for alkenes (anti-Markownikoff). Thus propenoic (acrylic) acid adds hydrogen bromide and water to form 3-bromo-and 3-hydroxypropanoic acids ... 

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... 

The hydration of alkenes (Scheme 2.10a) is a useful way of generating alcohols. In the acid-catalysed hydration of an alkene, the initial electrophilic attack by a proton affords the more stable carbenium ion (car-bocation), which is then neutralized by the attack of a water molecule. In the case of an unsymmetrical alkene this hydration follows the Markownikoff rule This rule states that the electrophilic part of the addendum becomes attached to the carbon atom that bears the greater number of hydrogen atoms. This generates the more stable, more highly substituted carbenium ion. 

A number of metals salts can be used as the source of electrophiles in reactions with alkenes. One of the most interesting of these involves the attack of mercury(II) acetate in acetic acid. Reductive cleavage of the organomercury compound with sodium borohydride leads to the overall hydration of the alkene in a Markownikoff sense. There are a number of preparative advantages, such as a reduced tendency to rearrange, associated with this and similar relatively mild procedures when compared to the direct protonation of a double bond (Scheme 3.14)... 

The acid-catalyzed hydration of alkynes (Table 6.7, example 2) is commonly carried out using mercury (11) salts, such as mercuric sulfate (HgS04), as catalysts. The addition (Scheme 6.67) appears to involve a bridged mercurinium ion, which, for unsymmetrical cases such as 1-alkynes other than ethyne (acetylene [HC CH]), is subsequently attacked by water (FI2O) at the carbon that best supports a positive charge. The regiochemistry of Markownikoff addition, seen with alkenes, is followed. 

The most synthetically valuable method for converting alkynes to ketones is by mercuric-ion-catalyzed hydration. Terminal alkynes give methyl ketones, in accordance with the Markownikoff rule. Internal alkynes will give mixtures of ketones unless some structural feature directs regioselectivity. Scheme 4.8 gives some examples of alkyne hydrations. 

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