Demercuration Subject

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. 

The reaction may be subject to limitations in the alkene structure similar to those of the nitrile process. Besides simple amides, one can also utilize urea and urethanes in this reaction. Demercuration is best effected by using alkaline sodium borohydride in the presence of a primary amine such as Bu"NH2. 

Numerous dienes and polyenes have been subjected to hydroxymercuration-demercuration.311 With nonconjugated dienes, the products can usually be predicted by applying what one has learned from the corresponding simple alkenes. Isolated double bonds are more reactive than conjugated double bonds and frequently one of the double bonds is sufficiently more reactive than the others that monohydroxy-lated products can be obtained. Improvements in selectivity have been reported by using mercury(II) tri-fluoroacetate339 or by adding sodium lauryl sulfate.340... 

The use of TEMPO to effect oxidative demercuration was originally demonstrated by Whitesides [16], and is attractive because it gives a functional handle for further structural elaboration. This technique was invoked by Kang in the syntheses of (-t-)-lactacystin and (-l-)-furanomycin [17]. For example, alkene 10 was subjected to mercurioamidation conditions to afford the cyclized organomercury intermediate 11 (Scheme 4). Treatment with lithium borohydride in the presence of TEMPO forms the unstable organomercury hydride. This fragments to release the primary carbon radical, which is trapped by TEMPO to yield the masked alcohol product 12, an intermediate in the synthesis of the neurotropic factor (-l-)-lactacystin. 

More familiar reactions but ones whose mechanism has been a controversial subject of interest for a long time have also been studied by this method. This is the case of the reductive demercuration of alkylmercuric halides by metal hydrides. In a careful study, Quirk was able to conclude that alkyl radicals are intermediates and that the process is a radical chain mechanism. This conclusion resulted from the knowledge that the cyclization was a relatively slow process (see Section XII.2) compared with the recombination process in the solvent cage, a conclusion recently confirmed by cidnp experiments. Furthermore, the use of metal deuterides and the measurement... 

The methanol can be replaced by other nucleophilic solvents such as ethanol, acetic acid, or water (in tetrahydrofuran as cosolvent) to give the corresponding ethoxy-, acetoxy-, or hydroxy-esters. Cyclic ethers (substituted tetrahydrofurans and tetrahydropyrans) are formed by intramolecular reaction when the unsaturated ester also contains an appropriately placed hydroxy-group, even in the presence of a reactive solvent. This has been developed into a procedure for the identification, analysis, and isolation of long-chain alcohols and acids having alkene unsaturation in positions 3 (trans only), 4 (cis or tram), or 5 (cis or trans) Such acids (or natural mixtures in which they are present) are reduced to alcohols and subjected to oxymercuration (in DMF as a non-participating solvent) and demercuration. Cyclic ethers are formed only when there is unsaturation at positions 3,4, or 5 other double bonds are unaffected. For example, methyl arachidonatc... 

---