Synthesis via mercuration

CHAPTER 4 ELECTROPHILIC ADDITIONS TO CARBON-CARBON MULTIPLE BONDS 

The mechanism of the reductive replacement of mercury by hydrogen using sodium borohydride as the reductant involves a free-radical intermediate generated 

The stereochemistry of oxymercuration has been examined in a number of systems. Conformationally biased systems such as 4-r-butylcyclohexene and 4-r-butyl-l-methylcyclohexene give exclusively the product of anti addition which is consistent with a mercurinium ion intermediate.This is normally the preferred 

The reactivity of alkenes toward mercuration varies over a considerable range and is governed by a combination of steric and electronic factors.Terminal double bonds are more reactive than internal ones. Disubstituted terminal olefins, however, are more reactive than monosubstituted cases, as would be expected for electrophilic attack. The differences in relative reactivities are large enough that selectivity can be achieved in certain dienes. Relative reactivity data for some pentene derivatives are given in Table 4.2. 

The addition of chlorine and bromine to alkenes is a very general reaction. Considerable insight has been gained into the mechanism of halogen addition 

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R, preparation usually by ring synthesis S, preparation by substitution Li, via lithio derivative Pd, via palladio derivative Hg, via mercuration. 

The first report of catalytic nitration via mercuration was a patent issued to Wolffenstein and Boeters (136] at the beginning of the century. They reported a procedure for the synthesis of dinitrophenol and picric add via oxynitration of benzene with mercuric nitrate and 50-55% nitric acid. The mechanism of oxynitration was delineated by Wesiheimer ei al. (137]. 

Recent studies have demonstrated (ref. 10) the potential synthetic utility of C-N bond formation via heteromercuration of carbamate derivatives of unsaturated amines. This prompted us to utilize the dehydration products 19a and 20a in the tropane synthesis via intramolecular heteromercuration. Thus the 1 1 mixture of 19a and 20a was treated with mercuric acetate followed by reduction with NaBH to furnish N-carbobenzoxynortropane (26) in 45% yield (based on reacted starting material). The product 26 must result from reductive demercuration of both organomer-curials 24 and 25 initially formed from the asymmetrical and symmetrical olefins 19a and 20a, respectively, via cationic intermediates 22 and 23 as depicted in Fig. 3. Thus separation of the olefin mixture is not necessary since both the olefins can equally be utilized as the reaction substrates in this cycliza-tion. 

Scheme 3.4. Synthesis of Alcohols, Ethers, and Amides via Mercuration...

Synthesis via scheme (2.53) has several drawbacks. The mercurated polystyrene is inclined to cross-link, and the polymer containing nitroso groups is unstable. A more suitable method of synthesis of spin-labelled polystyrene is given below [109] ... 

The mercuration-demercuration sequence was applied to the stereospecific synthesis of 2 deoxy-o-hexopyranoside derivative via a mercury(ll) trifluoroace-tate-promoted cyclization [54] (equation 25)... 

Examples involving the use of organomercury reagents as nucleophiles in aqueous media are also known. Bergstrom studied the synthesis of C-5-substituted pyrimidine nucleosides in aqueous media via a mercurated intermediate using Li2PdCl4 as a catalyst (Eq. 6.42).136... 

Alkenylzirconium compounds 34 obtained by the hydrometallation of alkynes were transformed to 1-alkenylboron compounds via transmetallation with B-halo-9-BBN or B-chlorocatecholborane62,63 (Scheme 5). Mercuration followed by transmetallation to BH3 was advantageous over the lithiation route in the synthesis of indole-3-boronic acid 35.64... 

However, for the synthesis of alkenylmercuric salts, one difficulty was encountered as mercuric acetate also reacted with the residual double bond. Fortunately, cyclohexene with mercuric acetate in tetrahydrofuran gave only 8 % reaction after 42 h1951. Thus, 2-(4-cyclohexenyl)-ethylmercuric chloride was obtained in 94% isolated yield via hydroboration-mercuration sequence of 4-vinyl cyclohexene (Eq. 123) 192). 

Another synthesis under physiological conditions has been reported (36). The piperidinoquinolizidine (LIII), obtainable from epilupinine via bromolupinine, cyclizes when dehydrogenated with mercuric acetate to a mixture of LIV and LV which on reduction with sodium borohydride gives a separable mixture of sparteine and allomatrine. The epimeric piperidinoquinolizidine obtainable from lupinine gives a mixture of fl -isosparteine (LVIII) and allomatridine (LVI). The dehydrogenation... 

An application of a related resin involves the synthesis of oligonucleotides via photolabile carbonate and carbamate anchors [230]. Photocleavable al-koxylbenzyl safety-catch solid supports Sr (Table 5) have been prepared [231,232]. Carboxylic acids were esterified by reaction with the secondary alcohol function of 5r and alcohols and amines could be attached via carbonate and carbamate derivatives, respectively. Unlike many previously reported photolabile linkers, these anchors were stable to irradiation with sunlight. In each case, product release was effected by treatment with mercuric chloride to remove the safety catch followed by irradiation with light of wavelength 350 nm, which leaves a benzofuran by-product tethered to the resin. 

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