Amino acid derivatives Lewis bases

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 asymmetric hydrosilylation of synthesized a-acetoxy-y3-enamino esters proceeded smoothly in the presence of a chiral Lewis base catalyst, (282), to provide a wide range of chiral a-acetoxy jS-amino acid derivatives in high yields with good diastereoselectivities and enantioselectivities." ° ... 

Recently, a dual organocatalysis approach, namely, the combination of the achiral nucleophilic Lewis base catalyst DMAP (23) and the chiral anion-binding thiourea catalyst 27, was applied to the Steglich rearrangement to provide a,a-disubstituted amino acid derivatives 24 in a highly enantioselective fashion (Scheme 43.5) [14]. Notably, replacement of the nucleophilic codiamino acid derivatives with excellent enantiomeric excesses (88-93% ee). 

A potential method for the preparation of novel amino acids via the highly selective addition of radicals to the glyoxylic oxime derivative of Oppolzer s camphor sultam (88) has been reported.181 Both Lewis acid and non-Lewis acid-mediated reaction conditions for the addition of alkyl radicals generated from alkyl iodides and Et3B/Bu3SnH were examined. A new chiral auxiliary based upon (R,R)-2,5-diphenylpyiTolidine has been used in the addition of phenylthiyl radicals to unsaturated methacrylamides. The selectivity was found to be better than that reported for the structurally related 2,5-dimethylpyrrolidine derivative.182... 

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]. 

Enantiomerically pure boron-based Lewis acids have also been used successfully in catalytic aldol reactions. Corey s catalyst (7.10a) provides good enantioselectivity with ketone-derived silyl enol ethers, including compound (7.11). Other oxazaborolidine complexes (7.13) derived from a,a-disubstituted a-amino acids give particularly high enantioselectivity, especially with the disubstituted ketene... 

Anhydro-alditols - The preparations of polyesters based on l,4 3,6-di-anhydro-D-glucitol and -o-mannitol with succinyl-, glutaryl- and adipoyl-dichlor-ides have been reported. Also reported have been the syntheses of poly(1 6)-2,5-anhydro-D-glucitol and its 3,4-di-0-alkylated derivatives by Lewis acid induced polymerization of 3,4-di-0-alkyl-l,2 5,6-dianhydro-D-mannitol base induced polymerization of l,2 5,6-dianhydro-3,4-di-0-methyl- or 3,4-di-O-iso-propylidene-D-mannitol base induced polymerization of l,2 5,6-dianhydro-3,4-di-O-pentyl- or di-O-decyl-o-mannitol and base induced polymerization of l,2 5,6-dianhydro-3,4-di-0-methyl-L-iditol. The solubilities of these 3,4-di-O-alkylated and deprotected polymers in aqueous and organic media were studied. Further, it has been reported that 2,5-anhydro-3,4-di-0-methyl-D-glucitol linked 1,6 to silica gel was useful for the optical resolution of amines and amino acid salts. ... 

---