Tishchenko reduction

Scheme 1.52. Proposed catalytic cycle for the cationic domino rearrangement/hetero-Tishchenko reduction process of secondary a-hydroxy epoxides in the presence of Sml2.

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, 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. 

The second total synthesis of swinholide A was completed by the Nicolaou group [51] and featured a titanium-mediated syn aldol reaction, followed by Tishchenko reduction, to control the C21-C24 stereocenters (Scheme 9-30). The small bias for anri-Felkin addition of the (Z)-titanium enolate derived from ketone 89 to aldehyde 90 presumably arises from the preference for (Z)-enolates to afford anti-Felkin products upon addition to a-chiral aldehydes [52], i.e. substrate control from the aldehyde component. 

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... 

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

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. 

Tishchenko Reduction of Carbonyl Derivatives. The samarium iodide-catalyzed Tishchenko reaction has been used quite extensively in synthesis. Interesting examples include the diastereoselective synthesis of anri-l,3-diols (eq 66) and 5-lactones (eq 67). ... 

Meerwein-Ponndrof-Verley reductions,Tishchenko reductions, Baeyer-Villiger oxidations, acetalization... 

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 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]... 

Lithium diphenylbinaphtholate catalyses enantioselective aldol-Tishchenko reactions to give 1,3-diols with three contiguous chiral centres. A successive aldol-aldol-Tishchenko version gave a triol (79) with five contiguous centres. An Evans-Tishchenko reduction is also described. " ... 

Schneider and Hansch used Zr(0 Bu) to catalyze the synthesis of acetone aldol adducts, 103, of aromatic aldehydes and diacetone alcohol, 102, (reaction 7.19) in moderate yields [69,70]. Moreover, they used it for rapid catalysis of Tishchenko reduction (reaction 7.20) of the P-hydroxyketones, 102, instantaneously get ahead the aldol reaction with some aliphatic aldehydes to yield the 1,3-awfi-diol monoesters, 104. 

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