Aldol-Tishchenko reaction catalyst

The first highly enantioselective cross-aldol-Tishchenko reaction of alkyl aryl ketones 28 and aldehydes was developed by the group of Shibasaki et al. [15]. With a chiral heterobimetallic lanthanide-based catalyst, this reaction was shown to proceed in typically very good enantioselectivity to furnish, after saponification of... 

Chiral lithium diphenylbinaphtholate (2) has been found to be an effective catalyst for the enantioselective aldol-Tishchenko reaction, affording 1,3-diol derivatives with three contiguous chiral centres and high stereoselectivities (up to 99% ee) ° A direct, highly enantioselective alkylation of arylacetic acids via enediolates using a readily available chiral lithium amide (3) as a stereodirecting reagent has been developed. This approach circumvents the traditional attachment and removal of chiral auxiliaries used currently for this type of transformation. 

The Aldol-Tishchenko reaction of enolizable aldehydes is a simple and effective way to prepare 1,3-diol monoesters. These esters are widely used as coalescing agents in the paint industry. The new process developed by Helsinki University uses monoal-coholates of 1,3-diols as catalysts giving fast and clean reactions, compared to the previous processes that used several inorganic catalysts. The rapid water-free method using microreactors allows fast preparation of these monoesters with high yields and minimum amounts of side products. 

Inspired by the earliest report of a Sml2-catalyzed Tishchenko reaction of P-hydroxyketones by Evans [150], and anyttrium-salen-complex-catalyzed asymmetric cross aldol-Tishchenko reaction by Morken and coworkers (Scheme 13.48) [151]. LLB catalyst was applied to direct catalytic asymmetric aldol-Tishchenko reactions. 

As discussed in Scheme 13.40, lanthanide metal source for preparing LLB solution was important, because contaminated side products are different depending on the lanthanide metal source. In the direct catalytic asymmetric aldol-Tishchenko reactions, the use of La(OTf)3 was effective, because LiOTf generated during catalyst preparation had positive effects on reactivity and selectivity. Use of a LLB-LiOTf... 

Table 13.38 Catalytic asymmetric aldol-tishchenko reactions using a La(OTf)3/(R)-BINOL/BuLi catalyst...

Zirconium alkoxide catalysts were used for the aldol-Tishchenko reaction shown in Equation 18 [23]. In the reaction, diacetone alcohol (55) is converted to the corresponding enol by removal of acetone, and adds to an aldehyde. Enantioselective version of the reaction was also examined [24]. 

Class II aldolase mimics (Scheme 10.4) were the first small-molecule catalysts that were reported for the direct intermolecular aldol reaction. These catalysts are characterized as bimetallic complexes that contain both Lewis acidic and Brpnsted basic sites. Shibasaki et al. first reported on the use of such a catalyst in the aldol reaction in 1997, demonstrating its potential with the reaction of various acetophenones 52 and aldehydes 53 (Scheme 10.13). Aldols 55 were obtained in good yields and enantioselectivities. A similar approach was used in the direct catalytic asymmetric aldol-Tishchenko reaction.Nevertheless, for the moment, this method does not provide access to true polypropionate fragments. ... 

A Tishchenko-aldol-transfer reaction was reported using (3-hydroxy ketones and an aldehydes with an AlMes catalyst, giving a mono acyl diol. ... 

Metallic components have also been added to a variety of heterogeneous oxide catalysts, to introduce additional hydrogenation, dehydrogenation and hydrogen transfer processes during aldolization, ketonization or Tishchenko reactions. Examples include acetone (propanone) to 4-methyl-pentan-2-one, ethanol to acetone and methanol to methyl formate (methyl methanoate), e.g. 

Other modifications of the Tishchenko reaction are also known, and catalytic cascade reactions are particularly interesting. Examples include combinations oflish-chenko with aldol reactions in the presence of achiral [169] and chiral catalysts [170], Tishchenko/esterification sequences [171], tandem semipinacol rearrangement/Tish-chenko reactions [172] and couplings of vinyl esters with aldehydes [173]. 

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