Aldol-Tishchenko reaction diastereoselective reactions

Mlynarski et al. [16] developed ytterbium-catalyzed enantio- and diastereoselective aldol-Tishchenko reactions of symmetrical dialkyl ketones as enol components for the first time. As chiral ytterbium ligand, they employed the amino alcohol 32, which gave rise to aldol-Tishchenko products such as 33 with up to 86% ee (Scheme 8.10). As documented by control experiments and very similar to the above discussed processes, the rate- and stereo-determining step in this reaction was proven to be the Tishchenko reduction with a rapid pre-retro-aldol equilibrium of the initially formed aldol products. This process may be utilized for reactions of alkyl aryl ketones as well, broadening its scope significantly. 

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. 

The synthesis began with Prins qrchzation of the symmetric vinylo-gous ester 273, prepared from heptadienol 272, followed by hydrolysis of the resulting trifluoroacetate and benzylation, to afford the desired 2,6-cis-tetrahydropyran 274 with 92 8 diastereoselection at C5 [113], By this novel desymmetrization, 2,4,6-all-ci5 trisubstituted pyran was efficiently provided. Boron-enolate aldol reaction, as Carreira did, of the methyl ketone 274 with aldehyde 275 gave hydroxy ketone 271 as a single isomer. In contrast to Car-reira s result, samarium-catalyzed intramolecular Tishchenko reduction [114]... 

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