Carbonyl Additions and Reductions

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. 

Several years later, more useful catalysts were described these were prepared from amino acids or dipeptides via their Schiff bases with 2-naphthol-l-carboxalde-hyde [13], The catalyst giving the highest induction for this reaction was prepared from the Schiff base 48 and trimethylaluminum. This catalyst resulted in moderate induction with several aldehydes including the three shown in Sch. 6. 

A bimetallic catalyst prepared from BINOL and lithium aluminum hydride has been found to result in useful asymmetric induction in the Pudovik reaction [17]. The (f )-ALB catalyst 64 (10 mol %) facilitates the addition of dimethyl phosphite to a variety of electron-rich and electron-poor aryl aldehydes in high yield with induction in the range 71-90 % ee. The nature of the solvent is important in this reaction—the induction for addition to benzaldehyde dropped from 85 % ee to 65 % ee when the solvent was changed from toluene to dichloromethane. Aluminum seems to be a key to the success of this reaction, because reaction with benzaldehyde was not as successful with other bimetallic catalysts. BINOL catalysts with lanthanum and potassium gave only 2 % ee, a catalyst with lanthanum and sodium gave a low 32 % ee, and a catalyst with lanthanum and lithium gave only a 28 % ee [18]. Aliphatic aldehydes were not successfully hydrophosphonylated with dimethyl phosphite by catalyst 64 (Sch. 9). Induction was low (3-24 % ee) for unbranched and branched substrates. a,/3-Unsaturated aldehydes were, however, reported to work nearly as well as aryl aldehydes with four examples in the range 55-89 % ee. The failure of aliphatic aldehydes with this catalyst can be overcome by reduction of the product obtained from reactions with a,)3-unsaturated aldehydes. As illustrated by the reduction of 67 with palladium on carbon, this can be done without epimerization of the a-hydroxy phos-phonate. 

A mechanism for this reaction has been proposed and is summarized in Sch. 10. The catalyst 64 is thought to be bifunctional with the aluminum center operating as a Lewis acid and the lithium naphthoxide operating as a Lowry-Brpnsted base. It was envisaged that the aldehyde coordinates with the aluminum to give the complex 69 and deprotonation of the dimethyl phosphite then gives the aggregate 70 in which the phosphite anion is positioned for P-alkylation of the aldehyde that will occur selectively from the si face when the catalyst is prepared from (f )-BINOL. 

Asymmetric reduction of carbonyls has also been achieved by Dupas and coworkers by reaction of achiral NADH equivalents mediated by chiral aluminum Lewis acids [23]. They reduced methyl benzoyl formate with the dihydropyrido[2,3-h]indole 86 and chiral aluminum Lewis acids whose structures are drawn and 89 and 90 (Sch. 12). Asymmetric induction was quite low. Details of the reaction, including the conditions used, were not provided nor were the procedures used for the preparation of the chiral Lewis acids 89 and 90. 

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