Demercuration, oxidative

Thus good yields of p-alkoxy alcdiols can be obtained, albeit as diastereomeric mixtures, but unfortunately hydtoxymercurated alkenes unda similar conditions do not lead to useful products. Despite this iqrparent limitation, alkoxymercuration-oxidative demercuration has been very effective in a number of systems described below, and there is no doubt it is a procedure worth consi ration for hydroxy group introduction. 

The synthesis of the limondd azadiradione, utiiizing a Hg° cyclization-oxidative demercuration sequence with an enol phosphate derived from trans,trans-famesol has been reported. Azadiradione, a te-tracarbocyclic memter of the iimonoid group isoiated from the neem tree, Azadirachta indica, has been converted to other tetracyclic limonoids, and is thus a key intermediate. The sequence is shown in Scheme 33. 

In the area of pheromone synthesis, oxymercuration-oxidative demercuration has also proven valuable. For example, all four stereoisomers (rf tetrahydro-2,2,6-trimethyi-2//-pyran-3-ol, from the eim bark beetle Pteleobius vittatus have been acquired by a sequence from (/ )- and (S)-sulcatol, which incorporates this mercury chemistry. The epimeric alcohols (47) and (48 Scheme 37) were separable (MPLC)... 

Oxymercuration-oxidative demercuration (OM-OD) has considerably broadened the utility of organo-mercurial applications in synthesis. Typically, a solution of the mercurial in DMF (room temperature) was added to a DMF solution of NaBH, through which oxygen was rapidly passed. Generally 1.2-1.3 mol of borohydride was required to effect complete demercuration. In addition to the expected alcohols and hydrocarbons, other products presumed to be alkoxyboron compounds were also formed, but these could be hydrolyzed to alcohols. A typical result is shown in equation (17), with yields after the hydrolysis step. 

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. 

The only side-reaction is the homo-coupling reaction of the parent diarylmercury which occurs as a result of oxidative addition of diarylmercury to palladium(O) followed by oxidative demercuration reaction. However, the selectivity can be enhanced by adding a nucleophilic catalyst, e.g. iodide ion. The role of iodide ion is apparently crucial as it significantly reduces the amount of symmetrical biaryl from the oxidative demercuration process. Since diarylmercurials act as two aryl-groups donors, only a half equivalent of aryl iodide is required for the cross-coupling reaction. 

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