Acetaldehyde silyl ketene

C2-symmetric bis(oxazolinyl)pyridine (pybox)-Cu (II) complex 27 has been shown to catalyze highly enantioselective Mukaiyaraa aldol reactions between (benzyloxy)acetaldehyde and silyl ketene acetals by Evans and co-workers as exemplified in Scheme 1-9 [38]. Here, the requirement for a chelating substituent on the aldehyde partner is critical to catalyst selectivity, as a-(terl-butyldimethylsil-oxy)acetaldehyde gave lower enantioselectivity (56% ee). In addition, P-(benzyl-oxy)propionaldehyde provided the racemic product, indicating a strict requirement for a five-membered catalyst-substrate chelate. 

Scheme 1-9. Ca-Symmetric copper (II) complex catalyzed enantioselective aldol addition of silyl ketene acetal to benzyloxy acetaldehyde.

The addition of propionate-derived enol silanes 140 deUvered 1,2-disubstitut-ed aldol adducts 141 and 142 in useful yields and selectivities (Eq. 17) [90]. As in the acetate-derived additions, the selectivity of the process was dependent on the thioalkyl substituent of the silyl ketene acetal 140. The 1,2-syn adduct was obtained from the addition of E-enolsilane and -butyl glyoxylate (Eq. 17, entry 3). Correspondingly, the formation of 1,2-anti adduct was observed in the addition of a-benzyloxy acetaldehyde and the Z-enol silane derived from the ferf-butyl thio ester. 

Aldol Reactions. The title reagent and its various congeners continue to find application in Mukaiyama-t3fpe aldol reactions as versatile nucleophilic propionate synthons with predictable behavior.For example, the ( )-isomer of the reagent produced the expected major isomer in a boron trifiuoride etherate mediated addition to a complex aldehyde en route to a C19-C35 subunit of swinholide A (eq 14). Remote stereoinduction in Mukaiyama aldol reactions of the reagent with (2-sulfinylphenyl)acetaldehydes was recently observed anti aldol adducts were obtained preferentially regardless of the geometry of the silyl ketene thioacetal employed. ... 

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