Addition Oxymercuration, Reduction

Oxymercuration-reduction of alkenes preparation of alcohols Addition of water to alkenes by oxymercuration-reduction produces alcohols via Markovnikov addition. This addition is similar to the acid-catalysed addition of water. Oxymercuration is regiospecific and auft -stereospecific. In the addition reaction, Hg(OAc) bonds to the less substituted carbon, and the OH to the more substituted carbon of the double bond. For example, propene reacts with mercuric acetate in the presence of an aqueous THF to give a hydroxy-mercurial compound, followed by reduction with sodium borohydride (NaBH4) to yield 2-propanol. 

Addition of alcohol to alkenes hy alkoxymercuration-reduction produces ethers via Markovnikov addition. This addition is similar to the acid-catalysed addition of an alcohol. For example, propene reacts with mercuric acetate in aqueous THF, followed hy reduction with NaBFl4, to yield methyl propyl ether. The second step is known as demercuration, where Flg(OAc) is removed hy NaBH4. Therefore, this reaction is also called alkoxymercura-tion-demercuration. The reaction mechanism is exactly the same as the oxymercuration-reduction of alkenes. 

In addition to the hydration reaction described in Section 11.3, the oxymercuration-reduction reaction can be used to add the elements of water to a carbon-carbon double bond in a two-step process. First the alkene is reacted with mercuric acetate, Hg(02CCH3)2, in water, followed by treatment with sodium borohydride in sodium hydroxide solution ... 

The overall result of the hydroboration-oxidation sequence is addition of water to an alkene with the opposite regiochemistry to that expected for a conventional acid-catalysed hydration. The usual way to do such a hydration is by oxymercuration-reduction. 

After the addition step is complete, the mercury is usually replaced by hydrogen, using a reducing agent. The net result is the addition of hydrogen and the nucleophile to the alkene, and the reaction is known as oxymercuration reduction. The regioselectivity is in the same sense as is observed for proton-initiated additions. ... 

In Section 4.5, you learned that water adds to an alkene if an acid catalyst is present. This is the way aUcenes are converted into alcohols industrially. However, under normal laboratory conditions, water is added to an alkene by a procedure known as oxymercuration-reduction. The addition of water by oxymercuration-reduction has two advantages over acid-catalyzed addition It does not require acidic conditions that are harmful to many organic molecules, and because carbocation intermediates are not formed, carbocation rearrangements do not occur. 

The overall reaction (oxymercuration-reduction) forms the same product that would be formed from the acid-catalyzed addition of water The hydrogen adds to the sp carbon bonded to the greater number of hydrogens, and OH adds to the other sp carbon. 

The tricyclic lactone, 163, was also transformed to a yohimbine precursor by Polniaszek and Stevens (Scheme 3.26). Treatment of 163 with methoxide induced a double bond migration which was followed by Michael addition of methoxide. Subsequent oxidation and thermolysis effected selenoxide elimination to provide 166. Ozonolysis of the double bond followed by reduction yielded a mixture of bis-hemiacetals which were reduced with triethylsilane in trifluoroacetic acid to provide the tricyclic pyran 167. Reduction of the lactone and tritylation of the primary alcohol function afforded 168 which was subjected to xanthate ester elimination to give the enol ether 169. Oxymercuration-reduction and detritylation afforded the methylpyranoside... 

The mercuric ion-catalyzed hydration of alkynes probably proceeds in a similar manner to the oxymercuration of alkenes (see Section 5.1). Electrophilic addition of Hg to the triple bond leads to a vinylic cation, which is trapped by water to give an vinylic organomercury intermediate. Unlike the alkene oxymercuration, which requires reductive removal of the mercury by NaBH4, the vinylic mercury intermediate is cleaved under the acidic reaction conditions to give the enol, which tautomerizes to the ketone. Hydration of terminal alkynes follows the Mai kovnikov rule to furnish methyl ketones. ° ... 

Addition of Water to Alkenes Oxymercuration 239 Addition of Water to Alkenes Hydroboration 242 Addition of Carbenes to Alkenes Cyclopropane Synthesis Reduction of Alkenes Hydrogenation 249... 

Oxymercuration of simple alkyl- and acyl-substituted cyclopropenes generally results in ring opening.Addition of mercury(II) acetate to 3-methyl-3-phenylcyclopropene, however, gave a low yield of a cyclopropane containing organomercury compound (15-20%), which was converted into an isomeric mixture of 1 -methoxy-2-methyl-2-phenylcyclopropanes by reduction with lithium aluminum hydride. Reaction of 5 with mercury trifluoroacetate in methanol and then sodium hydroxide led predominantly to one cylopropane. ... 

Oxymercuration, alkoxymercuration, and the addition of Br2 and CI2 form cyclic intermediates. Oxymercuration and alkoxymercuration are followed by a reduction reaction. Reduction increases the number of C — H bonds or decreases the number of C — O, C—N, or C—X bonds (where X denotes a halogen). Hydroboration is followed by an oxidation reaction. Oxidation decreases the number of C—H bonds or increases the number of C—O, C—N, or C—X bonds (where, again, X denotes a halogen). 

The synthesis of the enantiopure AB segment 184 [68] by Shibasaki et al. [178] relied on the enantioselective opening of the oxirane ring of the readily available meso-epoxide 177 with p-anisidine [179,180], followed by two steps with 1,3-chiraUty transfer. After extensive experimentation the best enantiomeric excess was obtained with a catalyst prepared from Pr(0-f-Pr)3-(Jl)-BINAP in the ratio 1 1.5 with three equivalents of triph-enylphosphine oxide as an additive. Thus, reaction of 177 with p-anisidine in the presence of 10 mol% of the chiral catalyst provided fraws-aminoalcohol 178 in 80% yield with a moderate enantiomeric excess (65% ee), which was raised to 95% ee by one recrystaUization in 40% yield (Scheme 36). Methy-lation of 178 and Hofmann degradation of the resulting quaternary salt with butyllithium at -78 °C gave aUyhc alcohol 179. Oxymercuration of alcohol 179 with Hg(OAc)2 in methanol, followed by sodium borohydride reduction [181]... 

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