Reductive demercuration

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 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. 

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... 

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

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)... 

There is persuasive evidence that reductive demercuration involves a noncage free radical chain mechanism with a common hydrogen source (RHgH) irrespective of the hydride employed (NaBHt, BusSnH, LAH) (equations 12-14). ... 

As fas as reaction conditions are concerned, two main approaches are usually taken. Either the nucleophilicity of the R5OH to be added is further enhanced by addition of base (normally R50 M +, or nitrogen bases of low nucleophilicity), i.e., base catalysis, or the electrophilicity of the accepting double bond is further increased by adding, e.g., mercuric salts (alkoxymercu-ration), or sources of halonium ions (formation of / -halohydrins). Clearly, the latter protocol, from now on abbreviated as "onium-methods , necessitates a subsequent step for the removal of the auxiliary electrophile, e.g., reductive demercuration of an intermediate /i-alkoxymercu-rial. Whereas base catalysis has successfully been employed with all varieties of acceptors, application of onium-methods thus far appears to be restricted to a,/ -unsaturated carbonyl compounds. Interestingly, conjugate addition of alcohols to a,/l-enones could also be effected photochemically in a couple of cases. 

One of the methods for the synthesis of alkyl azides is based on the regioselective addition of mercury(II) azide, generated from mercury(II) acetate and sodium azide, to alkenes in water/te-trahydrofuran (1 1) to afford /i-azidoalkylineiciiry compounds which are then reductively demercurated to alkyl azides5-7. Completely diastereoselective cis addition occurred with norbornene (exo addition)5 and cyclopropenes6. 

Cfclopropyl azides.- Mercuric azide adds. syn to cyclopropenes (1) to give cis-2-azidocyclopropylmercuric azide salt (2) in fair yield. Reductive demercuration with NaBH gives cyelopropyl azides (3) in moderate yield. 

Another example is mercurilactonization, which proceeds with good stereocontrol in the formation of both y- and 8-lactones, but suffers from elimination during the reductive demercuration. An exploration of a number of reagents and conditions, including NaBH and various pHs, hydrogen over Wilkinson s catalyst, Bu3SnH and NaaS, indicates that reductive elimination is minimized in alkali borohydride, although it cannot be avoided entirely (Scheme 28). ... 

Treatment of azido(2-azidocyclopropyl)mercury(II) derivatives with sodium borohydride under basic aqueous conditions led to concomitant C —Hg cleavage and C —H bond formation and formation of the corresponding azidocyclopropanes. Reductive demercuration also took place when (cw-2-azidocyclopropyl)bromomercury(II) derivatives were reacted with sodium amalgam and deuterium oxide mercury was replaced stereospecifically with deuterium leading to c -l-azido-2-deuteriocyclopropanes. The yields are generally very low (< 25%). 

Fig. 7). The ring closure also proved to be remarkably stereoselective. Thus intramolecular oxymercuration, followed by reductive demercuration, provided the tetrahydropyran (22, ring A of X-206) with the desired 2,6-cis-relative stereochemistry in excellent overall yield as a single diastereomer. 

The allyl alcohol 56 furnished 58 predominantly on oxymercuration in aqueous tetrahydrofuran followed by reductive demercuration using NaBH4 [31]. Assisted by chelation with both the ring oxygen and the carbinol function, mercuration on the a-face allows water to approach from the p-face, as shown in 57, to form the product 58 selectively. In aligning the methyl group on the double bond with the... 

Chain-extension at the Reducing End . Mercuricyclization of hept-dienitol 48 and subsequent reductive demercuration in the presence of oxygen afforded a 3 1 mixture of 1,2-unsaturated hept-3-ulofuranosides 49. Reaction of 5,6-0-isopropylidene-2,3-di-0-Tbdms-D-allono-l,4-lactone with allyl magnesium chloride, followed by acetylation, then ozonolysis or epoxidation gave octos-3-ulose derivative 50 and non-4-ulose derivatives 51, respectively. ... 

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. 

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