Amino acids as chiral ligands

Cross-linked polymers bearing IV-sulfonyl amino acids as chiral ligands were converted to polymer bound oxazaborolidine catalysts by treatment with borane or bromoborane. In the cycloaddition of cyclopentadiene with methacrolein, these catalysts afforded the same enantioselectivities as their non-polymeric counterparts238. 

Lewis-acid catalysis of Diels-Alder reactions involving bidentate dienophiles in water is possible also if the beneficial effect of water on the catalyzed reaction is reduced relative to pure water. There are no additional effects on endo-exo selectivity. As expected, catalysis by Cu ions is much more efficient than specific-acid catalysis.Using a-amino acids as chiral ligands, Lewis-acid enan-tioselectivity is enhanced in water compared to organic solvents. Micelles, in the absence of Lewis acids, are poor catalysts, but combining Lewis-acid catalysis and micellar catalysis leads to a rate accelaration that is enzyme-like. 

A promising Pd(II)-catalyzed enantioselective C—H activation reaction has been demonstrated using monoprotected a-amino acids as chiral ligands (Equation 11.32) [70]. The coordination of a chiral nitrogen atom at the metal center is believed to be crucial for the enantiocontrol. This approach opens the door for chiral recognition in the C—H activation step. 

As the follow up to our studies in connection to the development of Ti-cat-alyzed cyanide additions to meso epoxides [4], we developed the corresponding catalytic enantioselective additions to imines [5]. A representative example is shown in Scheme 1 chiral non-racemic products maybe readily converted to the derived cx-amino acids (not available through catalytic asymmetric hydrogenation methods). In these studies, we further developed and utilized the positional optimization approach effected by examination of parallel libraries of amino acid-based chiral ligands (e.g., 1 and 2). Thus, the facile modularity of these ligands and their ease of synthesis were further exploited towards the development of a new catalytic enantioselective method that delivers various ar-... 

Yamamoto has used the modularity of another type of oc-amino acid-based chiral ligand to promote enantioselective epoxidations of allylic alcohols [21]. Thus, as illustrated in Eq. (8), parallel libraries of various ligand candidates were prepared and the identity of the optimal ligand 13 was established through positional optimization. 

Novel bidentate chiral Lewis acids derived from 1.8-naphthalenediylbis(dichloroborane) and modified amino acids as chiral auxiliary have been successfully utilized as effective catalysts for the asymmetric Diels-Alder reaction of a,[ -unsaturated aldehydes. The enantioselectivity is highly sensitive to the kind of chiral amino acids. Moderate enantioselectivity was obtained with the tryptophan-derived ligand for the endo adduct, but amino acids without aromatic groups... 

Such cases can be encountered in the case of thin-layer chromatographic separation of amino acids, using copper complexes of long chain amino acids as chiral additives via a ligand exchange approach. The copper complexes of alkyl amino acid chiral additives are so strongly adsorbed on the RP stationary phase that they act as a chiral stationary phase [154-156]. 

A milestone in the use of this technique was the introduction of the N-(3,5-dinitrobenzoyl)amino acids as chiral immobilized CT-acceptor ligands. In particular, Pirkle et al. [43,44] prepared CSPs by covalently binding the chiral selector to a silica gel support and used them for the separation of several optical isomers by column chromatography. 

Pll The asymmetric synthesis of a-amino acids and derivatives is an important topic as a result of their extensive use in pharmaceuticals and agrochemicals and as chiral ligands. Many highly enantioselective approaches have been reported. Industrial production of a-amino acids via the Strecker reaction is historically one of the most versatile methods to obtain these compounds in a cost-effective manner, making use of inexpensive and easily accessible starting materials. (From Boesten et al., 2001)... 

The synthesis of a-amino acids is important because they are used extensively in pharmaceuticals, agrochemicals, and as chiral ligands. The Strecker reaction is historically one of the most versatile ways to synthesize a-amino acids, but this method yields only 50% of a single enantiomer. Higher yields can be achieved by using chiral auxiliaries, but auxiliaries are often high in cost and low in availability. 

Takemoto and his co-workers developed asymmetric allylic alkylation of allylic phosphates with (diphenyl-iminolglycinates as carbon-centered nucleophiles (Equation (56))/" " In this reaction system, use of optically active bidentate phosphites 142 bearing an (ethylthio)ethyl group as chiral ligands promotes the allylic alkylation, and chiral /3-substituted a-amino acids are obtained with an excellent enantioslectivity. 

TABLE 8 Effect of the Structures of L-Proline and D-Proline as Chiral Ligands on the Chiral Resolution of Amino Acids... 

Co(trien)(NH3)2] + has been isolated, and only the meso trans isomers (197-198) with two different axial ligands, remain to be distinguished. There is also an extensive chemistry of N and C-alkylated derivatives of (178 180) as cA-[Co(OH)(trien)(OH2)] assists the hydrolysis of amino acid esters, amino acid amides, and peptides to form cis-fi (194) and cA-jS2-[Co(OA0(trien)] + (195)(( A = amino acid) complexes. Chiral alkylated trien ligands have the potential for chiral stereospecificity in such reactions. 

Kobayashi et al. developed chiral Lewis acids derived from A -benzyldiphenylproli-nol and boron tribromide and used these successfully as catalysts in enantioselective Diels-Alder reactions [89]. The corresponding polymeric catalyst 71 was prepared and used for the Diels-Alder reaction of cyclopentadiene with methacrolein [90]. Different polymeric catalysts 72, 73, 74 were prepared from supported chiral amino alcohols and diols fimctionalized with boron, aluminum and titanium [88,90]. In these polymers copolymerization of styrene with a chiral auxiliary containing two polymerizable groups is a new approach to the preparation of crosslinked chiral polymeric ligands. This chiral monomer unit acts as chiral ligand and as a crosslink. 

Recently, the use of polymer-supported chiral ligands and poly(amino acids) as enantioselective elicitors during epoxidation has become popular. Thus, poly(tartrate ester) is for the Sharpless asymmetric epoxidation,poly-L-leucine for epoxidation of enones. 

Several methods for the epoxidation of a,(3-unsaturated carbonyl compounds have been reported. The use of amino acid derivatives or peptides as chiral ligands for epoxidation continues to be an active area of investigation. The use of silica bound poly-L-leucine, 21, with sodium percarbonate appears to be an excellent route to enantiomerically pure keto... 

---