Tischenko reduction

Woerpel has recently reported a tandem double asymmetric aldol/C=0 reduction sequence that diastereoselectively affords propionate stereo-triads and -pentads commonly found in polyketide-derived natural products (Scheme 8-2) [14], When the lithium enolate of propiophenone is treated with excess aldehyde, the expected aldolates 30/31 are formed however, following warming to ambient temperature a mono-protected diol 34 can be isolated. In a powerful demonstration of the method, treatment of 3-pentanone with 1.3 equiv of LDA and excess benzaldehyde yielded product in corporating five new stereocenters in 81% as an 86 5 5 3 mixture of diastereomers (Eq. (8.8)). A series of elegant experiments have shown that under the condition that the reaction is conducted, the aldol addition reaction is rapidly reversible with an irreversible intramolecular Tischenko reduction serving as the stereochemically determining step (32 34, Scheme 8-2). 

A stereoselective Tischenko reduction of P-hydroxyketones in the presence of a catalytic amount of Sc(OTf)3 has been described [155]. Aliphatic and aromatic substrates were reduced to 1,3-diol monoesters in moderate to high yields (38-93%) with high 1,3-anti diastereoselectivities (de = 76- > 95%). 

The above reversible equation indicates that one mol of aluminium iso-propoxlde will reduce directly three mols of the carbonyl compound. It is generally desirable to use excess of the reductant except for aromatic aldehydes for the latter side reactions (e.g., 2RCHO-----> RCOOCH R Tischenko re-... 

Zirconocene complexes, denoted Cp2ZrH2, are efficient catalysts in the Tischenko-type dimerization of aldehydes to esters 96 (Eq. 43) [45a], and the reaction has been modified to enable the stereoselective reduction of /1-hydroxyketones with aldehydes (Eq. 44) [45b]. 

Covalent Bonds R Al—0 / D Oxidation (Oppenauer Oxidation) Hydride Transfer (p-Hydride Elimination Meenwein-Ponndorf-Veriey Reduction) C-O Bond Formation (Tischenko Reaction) —Al—0 R... 

The initial radical addition reactions can also be sequenced with a second, nucleophilic reaction. Thus radical conjugate addition and subsequent reduction leads to an enolate. Enolates thus generated can undergo a variety of reactions [8] including aldol reactions [9], Claisen condensations, intramolecular Michael reactions, and intermolecular Tischenko redox processes (Eqs. 7, 8). 

The aldehyde groups of polyacrolein can be reduced by the Meerwein-Ponndorf reaction. There is a limit, however, to the amount of alcoholate that can be used and to the concentrations of free aldehyde groups in the starting material [256]. Also, ester condensations take place (Tischenko reaction) at the same time as the reductions occur [256]. 

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