Aldol reactions of ketene acetal

The first report of an aldol reaction mediated by a chiral aluminum Lewis acid described catalysts generated from the pinene diol 12 and the bornane amino alcohol 14 [7], The catalysts were generated by the reaction of each substrate with diethylalu-minum chloride and were evaluated in the Muikaiyama aldol reaction of the ketene acetal 7 with wo-valeraldehyde. The most successful of the two was catalyst 13 which gave the aldol adduct 8 in 66 % enantiomeric excess (ee) but only in 15 % yield with 20 mol % catalyst. Very recently, this reaction has been re-investigated with catalysts generated from type 16 bornane diols [7], The aldol reaction of ketene acetal 10 with dihydrocinnamaldehyde gave the adduct 11 in 58 % ee and 50 % yield with 100 mol % catalyst (Sch. 2). 

Although the asymmetric aldol reaction of benzaldehyde and di ketene has been reported with a catalyst generated from di-iso-propyl tartrate and iso-propanol, low induction and low yields were observed for the d-hydroxyl-y5-keto ester 27 [8], Low induction was also observed for aldol reactions mediated by chiral aluminum catalysts generated from a-amino acids [9]. These types of catalyst have been very successful when employing boron as the Lewis acid, as illustrated in the aldol reaction of ketene acetal 10 with the boron catalyst 31 derived from (5)-valine (Sch. 4) [9,10]. Catalysts derived from A-tosyl-(5 )-valine and Et2AlCl and i-BuyAl were relatively ineffective (< 15 % ee) [9]. 

This section reviews the literature on asymmetric carbonyl additions and reductions mediated by chiral aluminum Lewis acids. This does not include aldol reactions, cycloaddition reactions, and ene reactions, each of which will be covered in separate sections. The earliest such carbonyl addition reaction to be reported was, along with the Muikaiyama aldol reaction of ketene acetal 7 (Sch. 2), the addition of trimethylsi-lyl cyanide to o-valeraldehyde [6]. The catalyst 13 did not result in asymmetric induction as high in this reaction as it did with the Muikaiyama aldol reaction of ketene acetal 7 with wo-valeraldehyde (Sch. 2). The cyanohydrin 45 was isolated in 65 % yield as a 66 34 mixture of enantiomers only. 

A novel route to 2-deoxY-2-C-alkvl-erYthro-pentoses has been devised by way of aldol reaction of ketene acetals such as 1-tert-butyldimethylsilyloxy-l-methoxyprop-l-ene with 2,3-Q-isopropylidene-D-glyceraldehyde. The absolute configuration of the lactone (48), isolated from Marshallia tenuifolia. has been confirmed by its enantiospecific synthesis. The aem-dinethylated oxime (49) has been specifically functionalised by a cyclopalladation - oxidation sequence giving, by way of the characterised organopalladium intermediate (50), the acetate (51). A study of the conformations of 3-deoxy-3-C-methyl- and... 

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