Acetates organomercuries

Ammonium acetate Organomercury sulfides from organomercury acetates... 

Mercuration. Mercury(II) salts react with alkyl-, alkenyl-, and arylboranes to yield organomercurials, which are usehil synthetic intermediates (263). For example, dialkyhnercury and alkyhnercury acetates can be prepared from primary trialkylboranes by treatment with mercury(II) chloride in the presence of sodium hydroxide or with mercury(II) acetate in tetrahydrofuran (3,264). Mercuration of 3 -alkylboranes is sluggish and requires prolonged heating. Alkenyl groups are transferred from boron to mercury with retention of configuration (243,265). 

With mercuric acetate (Hg(OOCCH2)2), olefins and / fZ-butyl hydroperoxide form organomercury-containing peroxides (66,100). The organomercury compound can be treated with bromine or a mild reducing agent, such as sodium borohydride, to remove the mercury. 

The reactivity of mercury salts is a fimction of both the solvent and the counterion in the mercury salt. Mercuric chloride, for example, is unreactive, and mercuric acetate is usually used. When higher reactivity is required, salts of electronegatively substituted carboxylic acids such as mercuric trifiuoroacetate can be used. Mercuric nitrate and mercuric perchlorate are also highly reactive. Soft anions reduce the reactivity of the Hg " son by coordination, which reduces the electrophilicity of the cation. The harder oxygen anions leave the mercuric ion in a more reactive state. Organomercury compounds have a number of valuable synthetic applications, and these will be discussed in Chapter 8 of Part B. 

The organomercurial derivatives which are still in use in pharmacy are thiomersal and phenlymercuric nitrate or acetate (PMN or PMA) (Fig. 10.6). 

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... 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

Cyclization by amidomercuration has been reported (391). Reaction of N-methoxycarbonyl-6-aminohept-l-ene (211) with mercuric acetate gave the organomercurial (212). Reductive coupling of 212 with l-decen-3-one in the usual way gave the cis and trans isomers (213). Successive treatment of 213 with ethanedithiol, Raney nickel, and ethanolic hydrogen chloride afforded ( )-sole-nopsin A (Id, 2 parts) and its isomer (Ic, 3 parts), which were separable by preparative gas chromatography (GC) (Scheme 5) (391). 

Quite recently, new methods for stereocontrol in cyclizations of /V-acylami nomethyl ethers have been developed. N,0-acetals of type (19 Scheme 13) were prepared from the corresponding secondary allyl alcohol and the diastereomers were separated by chromatography and/or crystallization. Cyclization with mercury(II) salts and reduction of the organomercury intermediate proceeded with high stereocontrol exerted by the amidal stereogenic center, not the stereogenic center on the original alcohol.237 ... 

A functionalized mercury(II) compound like ethyl (acetoxymercurio)acetate (136) allows an easy approach to prostaglandin endoperoxide analogs (equation 52).204 Several organomercury(II) compounds, RHgCl (R = Me, aryl, benzylic), are able to add to 1,3-dienes in the presence of a stoichiometric amount of a palladium(II) salt and affonl ir-allylpalladium compounds of type (137) in variable yields (equation 53).20S A related intramolecular carbomercuration has been reported by Snider.206 It allows a stercospe-cific approach to the chloromercury compound (138 equation 54). Similar palladium-mediated reactions... 

Treatment of l-(mercaptoalkyl)silatranes with organomercury acetate in chloroform affords the corresponding mercury derivatives in 80-85% yield (equation 148). A related reaction with diorganylmercury results in lower product yields372. 

Over 35 years ago, Richard F. Heck found that olefins can insert into the metal-carbon bond of arylpalladium species generated from organomercury compounds [1], The carbopalladation of olefins, stoichiometric at first, was made catalytic by Tsutomu Mizoroki, who coupled aryl iodides with ethylene under high pressure, in the presence of palladium chloride and sodium carbonate to neutralize the hydroiodic acid formed (Scheme 1) [2], Shortly thereafter, Heck disclosed a more general and practical procedure for this transformation, using palladium acetate as the catalyst and tri-w-butyl amine as the base [3], After investigations on stoichiometric reactions by Fitton et al. [4], it was also Heck who introduced palladium phosphine complexes as catalysts, enabling the decisive extension of the ole-fination reaction to inexpensive aryl bromides [5],... 

Sometimes the reaction conditions used in this reaction are too harsh since heating is involved and rearrangement reactions can occur. A milder method that gives better results is to treat the alkene with mercuric acetate [Hg(OAc)2] then sodium borohydride. The reaction involves electrophilic addition of the mercury reagent to form an intermediate mercuronium ion. This reacts with water to give an organomercury intermediate. Reduction with sodium... 

Ozonolysis of the s-alkylmercuric halides and the di-s-alkylmercurials produced the coresponding ketone. Although some carbon-carbon cleavage occurred, it was generally less than with the reaction of the primary organomercurials (see Reactions 13 and 14, Table I). In partial contrast to the results of Bockemuller and Pfeuffer (Reaction II), the ozonation of diisopropylmercury yielded acetic acid in addition to acetone (Reaction 14, Table I). 

Mercuric acetate, Hg(02CCH3)2 Adds to alkenes in the presence of water, giving a-hydroxy organomercury compounds that can be reduced with NaBH4 to yield alcohols. The overall effect is the Markovnikov hydration of an alkene (Section 7.4). 

By treatment of a /1-lactam with mercury(II) acetate in tetrahydrofuran, a bicyclic [3.2.0] system, e.g., 9, was formed with total diastereoselectivity, the organomercurial was characterized by H... 

Lavina and coworkers i>42) have extensively studied the reaction of cyclopropanes with mercuric acetate. In water or methanol solution the product is an organomercury alcohol or methyl ether (Eq. (29)). Studies... 

An indirect hydration reaction may be performed using mercury(TI) acetate (Scheme 2.10b). The mercury salt behaves as the electrophile, forming an organomercury intermediate. The C Hg bond is subsequently cleaved by reduction with sodium borohydride and the alcohol is generated by hydrolysis of the acetate. 

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)... 

Sodium amalgam reduction of organomercurials in alkaline deuterium oxide gives products with stereospecific retention during the replacement of mercury by deuterium [71]. This was shown in the reduction of cw-8-acetoxymercuri- (Ila) and c75-8-chloromer-curidibenzobicylo[2.2.2]octadien-7-ol acetates (Ilb), /ra/75-8-chloromercuridibenzobicy-clo[2.2.2]octadien-7-ol, and some norbornyl derivatives. Reduction of these compounds with sodium borodeuteride gave products without stereospecific deuterium incorporation [71]. 

The two-stage process of oxymercuration-demercuration is fast and convenient, takes place under mild conditions, and gives excellent yields—often over 90%. The alkene is added at room temperature to an aqueous solution of mercuric acetate diluted with the solvent tetrahydrofuran. Reaction is generally complete within minutes. The organomercurial compound is not isolated but is simply reduced in situ by sodium borohydride, NaBH4. (The mercury is recovered as a ball of elemental mercury.)... 

In the laboratory, alkenes are often hydrated by the oxymercura-tion procedure. When an alkene is treated with mercurydl) acetate [Hg(02CCH3)2, usually abbreviated HgOAclal in aqueous tetrahydrofuran (THF) solvent, electrophilic addition to the double bond rapidly occurs. The intermediate organomercury compound is then treated with sodium boro-hydride, NaBH4, and an alcohol is produced. For example ... 

Treatment of an alkene with mercuric acetate in aqueous THF results in the electrophilic addition of mercuric ion to the double bond to form an intermediate mercuri-um ion. Nucleophilic attack by H2O at the more substituted carbon yields a stable organomercury compound, which upon addition of NaBH4 undergoes reduction. Replacement of the caiton-mercury bond by a carbon-hydrogen bond during the reduction step proceeds via a radical process. The overall reaction represents Markovnikov hydration of a double bond, which contrasts with the hydroboration-oxidation process. 

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