Mercury enolates aldol reaction

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... 

To achieve good yields excess of TMS enol ether 29 must be used. Although replacement of the required mercury salt would be desirable, this in situ preparation of the enolate and subsequent asymmetric aldol reaction is a practical method on a laboratory scale. 

The concept of Lewis base activation of Lewis acids was developed by Denmark, and it takes advantage of the fact that the Lewis acidity of silicon is increased when the coordination sphere is enlarged. If chiral Lewis bases are provided, here chiral phosphoramides and bisphosphoramide, SiCl can be efficiently employed in asymmetric Mukaiyama aldol reactions. The Lewis base activation can be performed on trichlorosilyl enolates (24), which can be generated in situ by mercury-mediated trans-silylalion of a TMS silyl enol ether (18) in the presence of SiCl. Generation of the hypervalent silicon species produces a more Lewis acidic silicon moiety, which acts to coordinate and activate the aldehyde that has to be brought to reaction (Scheme 2.128) [48]. 

One practical limitation is the availability, storage, and handling of reactive tri-chlorosilyl enolates. Addressing this issue, Denmark et al. developed an interesting, more practical procedure entailing in situ preparation of those reactive species. Starting from a TMS enol ether 29, in situ preparation of the trichlorosilyl enolate with tetrachlorosilane and mercury acetate, followed by subsequent asymmetric al-dol reaction, gave the aldol product (S)-25 in 89% yield and with 92% ee (Scheme 6.14). 

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