Evans-Tishchenko

In the total synthesis of a polyketide natural product, (+)-discodermolide (22), Paterson and co-workers synthesized the C9-C16 fragment 27 using a Johnson-Claisen rearrangement9 (Scheme 1.2i). Evans-Tishchenko reduction10 of... 

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. 

S.L. Schreiber and co-workers accomplished the total synthesis of (-)-rapamycin. In their approach, they utilized an Evans-Tishchenko reaction of C22-C42 fragment and Boc pipecolinal. The reaction provided the product with excellent yield and as a >20 1 mixture of the anti and syn diastereomers. 

Rhizoxin D, a natural product possessing potent antitumor and antifungal activity, was synthesized by J.W. Leahy and co-workers. " To establish the C17 stereocenter, they utilized the Evans-Tishchenko reaction. To this end, the 3-hydroxyketone substrate was reacted with p-nitrobenzaldehyde in the presence of catalytic Smb. The reaction yielded the monoester of the anti 1,3-diol as a single product. 

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... 

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. 

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. " ... 

Evans-Tishchenko reaction 41) gave the benzoate 28. Functional group manipulation then gave the aldehyde 29. A matched aldol reaction ( 3) between aldehyde 29 and the ( )-enolate 30 (derived from ketone 21), which presumably proceeds via TS 31, provided the anti adduct 32 ( 8% ds). This was then elaborated into the stannane 17. In this way, the introduction of the 6 contiguous stereocenters was achieved with essentially complete control. 

Hulme accomplished the model synthesis of the octalactin eight-membered ring system possessing a side chain by the Evans-Tishchenko intramolecular cyclization using the Sm(lll) reagent (Scheme 5.24) [70]. This unique strategy for accessing the... 

A similar strategy is employed when using the Evans-Tishchenko reaction [81]. The Tishchenko reaction that is first described in 1906 uses a Lewis acid-mediated disproportionation of two carbonyl moieties to form an ester. In 1990, Evans and Hoveyda reported on their variant, which involves a preformed p-hydroxy ketone and an 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... 

A related intramolecular reaction of this type is the so-called Evans-Tishchenko reaction [166]. Here, a P-hydroxy ketone is reduced in the presence of an aldehyde yielding 1,3-diol monoesters. Several metal catalysts such as samarium iodide [166, 167] and zirconocene complexes [168] are effective. The reaction is highly diastereo-... 

Scheme 9.1 Transition state of the intramolecular Evans-Tishchenko reaction...

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