Demercuration reduction

Ammonia can be added to double bonds (even ordinary double bonds) in an indirect manner by the use of hydroboration (15-16) followed by treatment with NH2CI or NH2OSO2OH (12-29). This produces a primary amine with anti-Markovnikov orientation. An indirect way of adding a primary or secondary amine to a double bond consists of aminomercuration followed by reduction (see 15-3 for the analogous oxymercuration-demercuration procedure), for example. 

Tri-n-butyltin hydride can also be used for reductive demercuration.20 An alternative reagent for demercuration is sodium amalgam in a protic solvent. Here the evidence is that free radicals are not involved and the mercury is replaced with retention of configuration.21... 

The particular example shown also has a special mechanism for stabilization of the cyclized carbocation. The adjacent acetoxy group is captured to form a stabilized dioxanylium cation. After reductive demercuration (see Section 4.1.3) and hydrolysis,... 

The threo stereoisomer was the major product obtained by the synthesis in Scheme 13.14. This stereochemistry was established by the conjugate addition in Step A, where a significant (4-6 1) diastereoselectivity was observed. The C(4)-C(7) stereochemical relationship was retained through the remainder of the synthesis. The other special features of this synthesis are in Steps B and C. The mercuric acetate-mediated cyclopropane ring opening was facilitated by the alkoxy substituent.19 The reduction by NaBH4 accomplished both demercuration and reduction of the aldehyde group. 

The reductive demercuration was marred by the loss of about half of the peroxide due to competing deoxymercuration which afforded 4-cycloocten-l-ol. An additional complication was the formation of a small amount of trans-1,2-epoxy-cw-cyclooct-5-ene. The bicyclic peroxide 50 was readily separated from the unsaturated alcohol by silica chromatography, but complete removal of the epoxide was more difficult. Preservation of the peroxide linkage was markedly higher in the bromodemercuration. The diastereoisomeric dibromoperoxides 51 were separated by HPLC, although only one isomer was fully characterised. 

Use of mild conditions was crucial and the development of diimide reduction of singlet oxygenates, silver-salt-assisted displacement of halide by peroxide nucleophiles, peroxymercuration and demercuration, peroxide transfer from organotin to alkyl triflates, and oxygen trapping of azoalkane-derived diradicals have all played a part in providing the rich harvest of new bicyclic peroxides described herein. 

The mercuration-demercuration reaction of cw,cw-l,5-cyclooctadiene (3) has been widely studied in order to get some insight into the synthesis of 9-oxa and 9-azabicyclo-nonane derivatives. However, the results of the reaction have often been the subject of some controversy since the ratio of the two isomeric bicyclo[3.3.1]- [199 and 201] and [4.2.1]- [198 and 200] nonanes, after reduction (equation 166), strongly depended on the reaction conditions of the mercuration step168,169. 

Demercuration of organomercury compounds is a critical step in synthetic procedures, which involve mercuration-initiated cyclization reactions [e.g. 41], Many of the standard procedures for demercuration result in rearrangement or ring cleavage of the system, but reductive carbon-mercury cleavage (e.g. Scheme 11.4) with an excess of the quaternary ammonium borohydride is effective under phase-transfer conditions [e.g. 42,43]. 

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 technique of methoxymercuration-demercuration was utilized to determine the position of double bonds in the side chains. Since this method is not successful with the free alkaloids (272), the secondary amino groups must be protected as the A -heptafluorobutyramide. These amides are treated with mercuric acetate and methanol followed by reduction with sodium borohydride to yield the methoxylated compounds (273). The mass spectra of these compounds show a fragment ion (274) at m/z 59 indicating terminal double bonds in every case (Scheme 22) 16,25,410,411). 

Although the mercuration step is stereospecific, the reductive demercuration step is not. and therefore neither is the overall reaction. 

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. 

Most useful of the demercuration procedures reported is the use of alkaline sodium borohydride244 or sodium-mercury amalgam.243 246 Reduction with UAIH4 affords the corresponding amines.24 ... 

Alkaline sodium borohydride is the preferred demercuration reagent, but sodium-mercury amalgam in D2O is best for stereospecific reduction with retention.268... 

While many different procedures have been reported for the hydroxymercuration—demercuration of alkenes, the most useful procedure uses mercury(II) acetate in aqueous THF, followed by in situ alkaline sodium borohydride reduction (equation 205).312-313 Virtually all substitution patterns about the C—C double bond are accommodated. 

The demercuration of (3-alkoxymercurials is usually best effected using alkaline sodium borohydride. Few rearrangements during this free radical reduction process have been observed 429 When the mercury moiety is positioned a to a carbonyl group, alkaline H2S430,431 or 1,3-propanedithiol316 provide alternatives that afford complementary stereochemical results (equation 262). The use of sodium-mercury amalgam is also useful for stereospecific reduction.432 433... 

Complicating side reactions may occasionally occur - as in the oxymercuration-demercuration of styrene to 1-phenylethanol for which experimental details are also given. In this case evidently some organomercurial compounds survive the reductive stage, and their subsequent decomposition during final distillation complicates the isolation of the pure product. 

Cumene (H donor) inhibits the symmetrization. The main direction becomes the reductive demercurization, because the R radicals controlling the process leave the sphere of the reaction (Singh Khanna 1983) ... 

E. Bettelli, P. Cherubini, P. D Andrea, P. Passacantilli, and G. Piancatelli, Mercuration-reductive demercuration of glycals A mild and convenient entry to 2-deoxy-sugars, Tetrahedron, 54 (1998) 6011-6018. 

Addition of mercury and an alkoxy group to a double bond, usually by a solution of mercuric acetate in an alcohol. Alkoxymercuration is usually followed by sodium borohydride reduction (demercuration) to give an ether, (p. 636)... 

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