Olefins oxymercuration

Unlike the oxymercuration of acyclic olefins, oxymercuration of bicyclic olefins often gives jy -addition products. Norbornenes 93, for example, show exclusive fvo-oxymercuration. In this reaction, the ratio between the isomers depends on the nature of the fvo-substituent (R1) and tro/o-substituent (R2) (Equation (36)). The presence of electron-withdrawing fvo-substituents always leads to a much greater selectivity in favor of 94a-d over 95a-d.116 117 As indicated by extensive theoretical calculations, the charge distribution in the transition states governs the selectivity of these reactions.118... 

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

Condensation of allyl isocyanate with succinimide affords the cyclic diacylurea 39. Acid hydrolysis leads to ring opening of the succinimide (40). Oxymercuration of the terminal olefin bond with mercuric acetate in methanol solution affords the diuretic meralluride (41). ... 

Vn. Oxymercuration A Convenient Route to Markovnikov Hydration of Olefins... 

Monoalkylthallium(III) compounds can be prepared easily and rapidly by treatment of olefins with thallium(III) salts, i.e., oxythallation (66). In marked contrast to the analogous oxymercuration reaction (66), however, where treatment of olefins with mercury(II) salts results in formation of stable organomercurials, the monoalkylthallium(III) derivatives obtained from oxythallation are in the vast majority of cases spontaneously unstable, and cannot be isolated under the reaction conditions employed. Oxythallation adducts have been isolated on a number of occasions (61, 71,104,128), but the predominant reaction pathway which has been observed in oxythallation reactions is initial formation of an alkylthallium(III) derivative and subsequent rapid decomposition of this intermediate to give products derived by oxidation of the organic substrate and simultaneous reduction of the thallium from thallium(III) to thallium(I). The ease and rapidity with which these reactions occur have stimulated interest not only in the preparation and properties of monoalkylthallium(III) derivatives, but in the mechanism and stereochemistry of oxythallation, and in the development of specific synthetic organic transformations based on oxidation of unsaturated systems by thallium(III) salts. 

Fig. 22 Divergent trends in the reactivity of various olefins in bromination with Br2 and in oxymercuration with Hg(OAc)2. Reproduced with permission from Ref. 264.

OXYMERCURATION-REDUCTION ALCOHOLS FROM OLEFINS 1-METHYLCYCLOHEXANOL, 53, 94... 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

This method, which is applicable to mono-, di-, tri-, and tetraalkyl as well as phenyl-substituted olefins, gives almost complete Markovnikov addition. Hydroxy, methoxy, ace-toxy, halo, and other groups may be present in the substrate without, in general, causing difficulties.147 When two double bonds are present in the same molecule, the use of ultrasound allows oxymercuration of the less-substituted one without affecting the other.148... 

Alkenes participate readily in oxymercuration with increasing alkyl-substitution resulting in decreasing reactivity.489,491,492 The oxymercuration of alkenes is usually an anti process.493 195 Exceptions are strained bicyclic olefins, such as norbomene495,496 [Eq. (6.83)],497 and frans-cyclooctene and frans-cyclononene.494... 

Sometimes a yellow color (mercuric oxide) appears at this point and disappears as the reaction proceeds. If the yellow color does not disappear in about 10 minutes, 1.5 ml. of 70% perchloric acid per mole of mercuric acetate may be added to accelerate the reaction. Under these conditions even unreactive olefins are completely oxymercurated in about an hour. 

Oxymercuration of alkenes is an electrophilic reaction involving the addition of mercuric salt and of a protic solvent (alcohols) according to reaction 9. UV/VIS spectrophotometric investigation of the olefin/mercuric salt reaction mixtures in methylene chloride provides evidence of the presence of an electron donor-acceptor complex between olefin and mercuric salt110 which is considered to be on the reaction pathway of the oxymercuration. 

It is clear that the mechanism in Scheme 25 parallels (at least from the qualitative point of view) the mechanism of the addition of bromine to olefins shown in Scheme 11. Kinetic investigations indicate that the oxymercuration reaction involves a series of fast equilibria until the mercuronium ion (53) is formed. The subsequent nucleophilic attack of the solvent is probably the rate-limiting step, as indicated by steric requirements in bulky alkenes111. In the bromine addition, the formation of the bromonium ion is the rate-limiting step (or the rate-limiting equilibrium). However, the olefin reactivities in both reactions (bromination and oxymercuration) are identical when steric effects in the TS of the two addition reactions are taken into account110. 

Both, hydration and hydroalkoxylation of olefins are usually carried out under acid catalysis or by oxymercuration reactions, although reactions mediated by palladium or by other metals have recently begun to emerge. In the latter case, nucleophilic addition of the O—H group is favored by a cationic palladium species that activates... 

CHAPTER 8 Ionic Addition of HX to an Alkene 332 Free-Radical Addition of HBr to Alkenes 334 Acid-Catalyzed Hydration of an Alkene 338 Oxymercuration of an Alkene 340 Hydroboration of an Alkene 345 Addition of Halogens to Alkenes 350 Formation of Halohydrins 352 Epoxidation of Alkenes 360 Acid-Catalyzed Opening of Epoxides 362 Olefin Metathesis 376... 

Oxymercaration (2, 265-267 3. 194). Brown and Geoghegan have investigated the relative reactivities of a number of olefins in the oxymercuration reaction in a 20 80 (v/v) mixture of water and THF. The following reactivity is observed terminal disubstituted > terminal monosubstituted > internal disubstituted > internal trisub-stituted > internal leirasubstitu ted. Thus steric factors play a major role in the reactivity of olefins. Increased substitution on the double bond and increased steric hindrance at the site of hydroxyl or mercury substituent attachment decrease the rate of reaction. In the case of olefins of the type RCH CHR, cts-oleiins are more reactive than the corre.sponding rra/i.s-olefins. Inclusion of the double bond in ring systems causes a moderate rate increase which varies somewhat with structure cyclohcxenc > cyclo-pentenc cyclooctene norbornene bicyclo[2.2.2]-octene-2. 

Because the possibility of olefinic isomerization still loomed important in considering product distributions, we decided to add the powerful olefin isomerization catalyst (17), rhodium trichloride, to the system. No change in product distribution from that of palladium chloride alone was found with either hexene or 2-hexene when a 1 1 molar ratio of rhodium trichloride/palladium chloride was used (Table VII). This is further evidence that the relative rate of vinylation is greater than that of isomerization. When rhodium chloride was used with hexene without any added palladium chloride at 115°C., only slight reaction occurred, and the product contained 85.7% 2-acetate, 10.2% 1-acetate, and 4.1% 3-acetate. Apparently, vinylation had occurred with rhodium trichloride in a manner analogous to oxymercuration and the low-temperature palladium vinylation reaction. 

Olefins can be converted into ketones by oxymercuration followed by transmetalation of the oxymercurial with palladium chloride. Unlike oxymercurials, the analogous palladium compounds decompose in solution to give ketones and palladium metal.4... 

Ketalization of 33 with ethylene glycol, oxymercuration of the terminal olefin, and reduction produced monomeric hydroxy acid 17 in 42% overall yield. 

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