The Evans-Tishchenko Reduction

Syn selective reductions Anti selective reductions The Evans-Tishchenko reduction Kinetic diastereoselection of 1,3-diols Aldol revisited... 

Our existing route to the C10-C16 aldehyde fragment was clearly not appropriate for this new plan. Reduction of )3-hydroxyketone ent-26 with triacetoxyborohydride proffered a 1,3-diol intermediate (ent-27) with no obvious means available for distinguishing the two secondary carbinol moieties. On the other hand, the Evans-Hoveyda variant of the classical Tishchenko reduction would provide a method to effect diastereoselective reduction of ent-26 while at the same time allowing differentiation of the C13 and C15 hydroxyl groups. According to the Evans-Tishchenko reduction protocol, a /3-hydroxyketone 80 is treated with an aldehyde and a catalytic quantity of Sml2 (Scheme 14). Transfer of hydride from the... 

The samarium-catalyzed reduction was utilized in the asymmetric synthesis of the marine macrolide bryostatin 2 (42) to furnish an intermediate (46)12 (Scheme 4.21). The ketone 43 underwent an aldol reaction with the ketoaldehyde 44 via the isopinylboryl enolate to give the aldol adduct 45 in good yield and 93 7 diastereoselectivity. Subsequent samarium-catalyzed Evans-Tishchenko reduction of the (3-hydroxy ketone 45 provided the p-nilrobenzoale 46 with excellent stereoselectivity. Silylation and saponification readily converted compound 46 into the alcohol 47 in 88% yield over two steps. 

Evans-Tishchenko reduction of ent-26 with cither p-nitrobenzaldehyde or benzaldehyde itself afforded benzoates 84 and 85, respectively, in good yield and with complete diastereoselectivity in each case. Interestingly, the same reaction, when attempted with / -anisaldehyde, gave none of the expected p-methoxybenzoate 86. Failure of this reaction may reflect the lower propensity of p-anisaldehyde to form hemiacetals owing to its poor electrophilicity. Alternatively, the in situ generation of a Sm(lll) "pinacolate" catalyst from Sml2 and p-anisaldehyde may be hampered by the relatively high reduction potential of this electron rich aldehyde. 

The so-generated ester serves at the same time as a protecting group and renders the Evans-Tishchenko reaction a transformation in natural product syntheses. Scheme 2.146 shows a typical combination of Paterson aldol reaction followed by anti-selective reduction. The DlPCl-mediated aldol reaction sets the configuration at the new secondary alcohol (102). This configuration is then used for the... 

Evans, D. A., Hoveyda, A. H. Samarium-catalyzed intramolecular Tishchenko reduction of 3-hydroxy ketones. A stereoselective approach to the synthesis of differentiated anti 1,3-diol monoesters. J. Am. Chem. Soc. 1990, 112, 6447-6449. 

SCHEME 14. The Evans-Hoveyda variant of the Tishchenko reduction. 

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