Aldol reactions aluminum-mediated

The first report of an aldol reaction mediated by a chiral aluminum Lewis acid described catalysts generated from the pinene diol 12 and the bornane amino alcohol 14 [7], The catalysts were generated by the reaction of each substrate with diethylalu-minum chloride and were evaluated in the Muikaiyama aldol reaction of the ketene acetal 7 with wo-valeraldehyde. The most successful of the two was catalyst 13 which gave the aldol adduct 8 in 66 % enantiomeric excess (ee) but only in 15 % yield with 20 mol % catalyst. Very recently, this reaction has been re-investigated with catalysts generated from type 16 bornane diols [7], The aldol reaction of ketene acetal 10 with dihydrocinnamaldehyde gave the adduct 11 in 58 % ee and 50 % yield with 100 mol % catalyst (Sch. 2). 

Although the asymmetric aldol reaction of benzaldehyde and di ketene has been reported with a catalyst generated from di-iso-propyl tartrate and iso-propanol, low induction and low yields were observed for the d-hydroxyl-y5-keto ester 27 [8], Low induction was also observed for aldol reactions mediated by chiral aluminum catalysts generated from a-amino acids [9]. These types of catalyst have been very successful when employing boron as the Lewis acid, as illustrated in the aldol reaction of ketene acetal 10 with the boron catalyst 31 derived from (5)-valine (Sch. 4) [9,10]. Catalysts derived from A-tosyl-(5 )-valine and Et2AlCl and i-BuyAl were relatively ineffective (< 15 % ee) [9]. 

This section reviews the literature on asymmetric carbonyl additions and reductions mediated by chiral aluminum Lewis acids. This does not include aldol reactions, cycloaddition reactions, and ene reactions, each of which will be covered in separate sections. The earliest such carbonyl addition reaction to be reported was, along with the Muikaiyama aldol reaction of ketene acetal 7 (Sch. 2), the addition of trimethylsi-lyl cyanide to o-valeraldehyde [6]. The catalyst 13 did not result in asymmetric induction as high in this reaction as it did with the Muikaiyama aldol reaction of ketene acetal 7 with wo-valeraldehyde (Sch. 2). The cyanohydrin 45 was isolated in 65 % yield as a 66 34 mixture of enantiomers only. 

Whereas a lower temperature is essential to mediate deprotonation with DATMP, diisobutyl aluminum phenoxide requires quite a high temperature (THF, reflux) to generate the aluminum enolates, with the aid of a shght excess of pyridine (Scheme 6.24) [44], Self aldol condensation of ketone 47 proceeded with acceptable yield under these conditions. An efficient synfhesis of tfl-muscone was achieved by way of an intramolecular aldol reaction by use of these reagents. 

Aluminum oxide has been one of the most frequently used reagents for self-condensation of ketones and aldehydes. However applications of aluminum-mediated aldol reactions to cross-coupling have appeared only recently in the literature. Aluminum reagents, in common with other Lewis acids, form aldol product chelates so that unwanted side reactions such as dehydration or secondary condensation may be avoided. ... 

In 1974, Jeffery et al. reported the first use of well-defined dimeric or trimeric aluminum enolates in the aldol reaction. - Reaction of dimethyl-Z(0)-4,4-dimethylpent-2-en-2-oxyalane (123) with acetaldehyde or benzaldehyde provides the anti aldol products (124) as chelated dimers involving five-coordinate aluminum atoms, as shown in Scheme 51. However, the corresponding (0)-enolate (125) gives dimeric products of syn configuration which undergo isomerization, if not hydrolyzed immediately, to provide the same anti products. This syn-anti isomerization is much more facile with benzaldehyde, and is in sharp contrast to aldol reactions mediated by boron. 

Davies and Liebeskind independently prepared chiral aluminum enolates from enantiomerically homogeneous acyl-iron complexes (137) and recorded the first aluminum-mediated asymmetric aldol reactions. Although the lithium enolate of the chiral iron complex (CHIRAC) provides aldol products with... 

As an early example of asymmetric aldol reaction mediated by chiral aluminum Lewis acids, Fujisawa and Shimizu reported the use of several catalysts generated from a series of chiral bornane type diols or the related amino alcohols (Scheme 6.22)... 

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