Imines amino acids-derived chiral Lewis

In 1997, the first truly catalytic enantioselective Mannich reactions of imines with silicon enolates using a novel zirconium catalyst was reported [9, 10]. To solve the above problems, various metal salts were first screened in achiral reactions of imines with silylated nucleophiles, and then, a chiral Lewis acid based on Zr(IV) was designed. On the other hand, as for the problem of the conformation of the imine-Lewis acid complex, utilization of a bidentate chelation was planned imines prepared from 2-aminophenol were used [(Eq. (1)]. This moiety was readily removed after reactions under oxidative conditions. Imines derived from heterocyclic aldehydes worked well in this reaction, and good to high yields and enantiomeric excesses were attained. As for aliphatic aldehydes, similarly high levels of enantiomeric excesses were also obtained by using the imines prepared from the aldehydes and 2-amino-3-methylphenol. The present Mannich reactions were applied to the synthesis of chiral (3-amino alcohols from a-alkoxy enolates and imines [11], and anti-cc-methyl-p-amino acid derivatives from propionate enolates and imines [12] via diastereo- and enantioselective processes [(Eq. (2)]. Moreover, this catalyst system can be utilized in Mannich reactions using hydrazone derivatives [13] [(Eq. (3)] as well as the aza-Diels-Alder reaction [14-16], Strecker reaction [17-19], allylation of imines [20], etc. 

The examples outlined in this chapter show that carbohydrates are efficient stereodifferentiating auxiliaries, which offer possibilities for stereochemical discrimination in a wide variety of chemical reactions. Interesting chiral products are accessible, including chiral carbo- and heterocycles, a- and 3-amino acid derivatives, 3-lactams, branched carbonyl compounds and amines. Owing to the immense material published since the time of the earlier review articles on carbohydrates in asymmetric synthesis [9,10], the examples discussed in this chapter necessarily focused on the use of carbohydrates as auxiliaries covalently linked to and cleavable from the substrate. Given the scope of this chapter, a discussion of other interesting asymmetric reactions has not been permitted — for example, reactions in which carbohydrate-derived Lewis acids, such as cyclopentadienyl titanium carbohydrate complexes, exhibit stereocontrol in aldol reactions [180]. Similarly, processes in which in situ glycosylation induces reactivity and stereodifferentiation — for example, in Mannich reactions of imines [181] — have also been excluded from this discussion. 

The assymetric Strecker reaction of diverse imines, including aldimines as well as ketoimines, with HCN or TMSCN provides a direct access to various unnatural and natural amino acids in high enantiomeric excesses, using soluble or resin-linked non-metal Schiff bases the corresponding chiral catalysts are obtained and optimized by parallel combinatorial library synthesis [93]. A rather general asymmetric Strecker-type synthesis of various imines and a, 9-unsaturated derivatives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-containing complexes [94]. When chiral (salen)Al(III) complexes are employed for the hydrocyanation of aromatic substituted imines, excellent yields and enatio-selectivities are obtained [94]. 

Lewis acid-catalyzed (EtAlCla, ZnClz) aza Diels-Alder reaction of imines derived from amino acid esters or carbohydrates with Danishefsky s diene provide precursors of chiral piperidine alkaloids. When using imines derived from 0-pivaloylated glycosylamines and ZnCl2 as Lewis acid, highly diastereoselective tandem-Mannich-Michael reactions are observed. The carbohydrate moiety is easily removed by treatment with HCl/MeOH. By employing galactopyranosylamine or arabinosylamine derivatives both enantiomeric series are readily available. 

Enamines of cyclohexylamine have been enantioselectively cyclized to bicyclo[3.3.1] nonanedione systems, using acryloyl chloride and chiral pyrrolidine catalysis. Enantio-pure A-sulflnylimines have been used in asymmetric synthesis of isoquinolone alkaloids, and a stereocontrolled synthesis of 3,4,5,6-tetrahydropyrimidine-based amino acids from imino ethers has been reported. Diastereoselective additions of chiral acetals of (2-lithiophenyl)acetaldehyde to arylimines have been used in an asymmetric synthesis of 1-aryltetrahydroisoquinolines. " Organolithiums react with chiral imines, in the presence of Lewis acids or bases, to give amines in up to 100% de. Diastereoselective additions of copper reagents to imines derived from (5)-l-phenylethylamine have been reported. 

Silyl cyanides react enantioselectively with such electrophiles as aldehydes, ketones, imines, activated azines, or,/ unsaturated carbonyl compounds, epoxides, and aziridines in the presence of chiral Lewis acid catalysts to give functionalized nitriles, versatile synthetic intermediates for hydroxy carboxylic acids, amino acids, and amino alcohols (Tables 3-6, 3-7, 3-8, and 3-9, Figures 3-6, 3-7, and 3-8, and Scheme 3-154). ° Soft Lewis acid catalytst, the reaction of epoxides with trimethylsilyl cyanide often leads to isonitriles, which are derived from silylisonitrile spiecies (Schemes 3-155 and 3-156). Soft Lewis base such as phosphine oxide also catalyzes the reaction and cyanohydrin silyl ethers of high ee s are isolated. 

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