Applications in Asymmetric Synthesis

Asymmetric synthesis is a stimulating academic challenge, but since it has become clear that most chiral drugs can be administered safely only in the enantiomerically pure form, the industrial need for asymmetric methods has made research in asymmetric synthesis absolutely necessary [5]. This has driven a renaissance in the discipline of organic chemistry, because all of the old-established reactions need to be reinvestigated for their application in asymmetric synthesis [6]. This has also applied... 

It is interesting to speculate that asymmetric induction may be the consequence of the exo anomeric effect, a stereoelectronic effect that favors the conformation 5 that places the aglycone O-C bond antiperiplanar to the pyran C(1) —C(2) bond7fi. Related asymmetric induction has also been observed in aldehyde addition reactions of the related, but racemic, pinacol (Z)-y-(tetrahydropyranyloxy)allylboronate49. As indicated in the examples above, however, the level of diastereoselectivity is modest and the only application in asymmetric synthesis is Wuts exo-brevicomin synthesis75. 

Many other known pyruvate lyases are unsuited to application in asymmetric synthesis since they catalyze C-C bond formation with random stereochemistry30. 

The synthetic elaboration of cis-dioxygenated dienes has flourished in the past two decades and several total syntheses have beenaccomplishedutilizingthesechiral building blocks. Both substrate acceptance and applications in asymmetric synthesis have been comprehensively reviewed, also providing a historical perspective [220,223,224]. 

From Biomimetic Concepts to Applications in Asymmetric Synthesis... 

P. Bako, K. Vizvardi, S. Toppet, E. V. der Eycken, G. J. Hoonaert, L. Toke, Synthesis, Extraction Ability and Application in Asymmetric Synthesis of Azacrown Ethers derived from D-Glucose , Tetrahedron 1998, 54, 14975-14988. 

The studies of the reactivity of saturated pyrrolo[2,l- )oxazoles are in general associated with the reactivity of Meyers chiral bicyclic lactams and their applications in asymmetric synthesis. 

In the last two decades optically active sulfur compounds have found wide application in asymmetric synthesis. This is mainly because organic sulfur compounds are quite readily available in optically active form. Moreover, the chiral sulfur groupings that induce optical activity can be removed from the molecule easily, under fairly mild conditions, thus presenting an additional advantage in the asymmetric synthesis of chiral compounds. This section deals with reactions in which asymmetric induction in transfer of chirality from sulfur to other centers was observed. This subject has been treated only in a cursory manner in recent reviews on asymmetric synthesis (290-292). 

Bennani, Y. L. Hanessian, S. trani-l,2-Diaminocyclohexane derivatives as chiral reagents, scaffolds, and ligands for catalysis Applications in asymmetric synthesis and molecular recognition. Chem. Rev. 1997, 97, 3161-3195. 

Berkessel A, Groger H (2005) Asymmetric organocatalysis - from biomimetic concepts to applications in asymmetric synthesis. Wiley, Weinhem... 

The use of tartrate esters was an obvious place to start, especially since both enantiomers are readily available commercially and had already found widespread application in asymmetric synthesis (Figure 11) (e.g.. Sharpless asymmetric epoxidation).23.24 Reagents 36-38 are easily prepared and are reasonably enantioselective in reactions with achiral, unhindered aliphatic aldehydes (82-86% ee) typical results are given in Figure 12.3c,h Aromatic and a,p-unsaturated aldehydes, unfortunately, give lower levels of enantioselection (55-70% e.e.). It is also interesting to note that all other C2 symmetric diols that we have examined (2,3-butanediol, 2,4-pentanediol, 1,2-diisopropylethanediol, hydrobenzoin, and mannitol diacetonide, among others) are relatively ineffective in comparison to the tartrate esters (see Table ll).25... 

With respect to practical applications in asymmetric synthesis, the four stereo-chemically distinct dihydroxyacetone phosphate (DHAP, 1)-dependent enzymes had been particularly appealing to us because these enzymes control the creation of two new asymmetric centers at the termini of a newly formed C-C bond, thus allowing an effective stereocombinatorial synthesis of stereoisomers (Scheme 2.2.5.1) [1, 3]. The individual aldolases are involved in the reversible cleavage of... 

Berkessel, A. and Groger, H. (2005) Asymmetric Organocatalysis from Biomimetic Concepts to Applications in Asymmetric Synthesis, Wiley-VCH Verlag GmbH, Weinheim. 

An asymmetric C-C coupling, one of the most important and challenging problems in synthetic organic chemistry, seems to be most appropriate for the creation of a complete set of diastereomers because of the applicability of a convergent, combinatorial strategy [38-40]. In Nature, such reactions are facilitated by lyases which catalyze the (usually reversible) addition of carbo-nucleophiles to C=0 double bonds, in a manner mechanistically most often categorized as aldol and Claisen additions or acyloin reactions [41], The most frequent reaction type is the aldol reaction, and some 30 lyases of the aldol type ( aldolases ) have been identified so far [42], of which the majority are involved in carbohydrate, amino acid, or hydroxy acid metabolism. This review will focus on the current state of development of this type of enzyme and will outline the scope and limitations for their preparative application in asymmetric synthesis. 

Reviews have appeared on the use of cycloaddition reactions in organic synthesis1 and on asymmetric cycloaddition reactions and their application in asymmetric synthesis of natural products.2... 

However, in spite of its wel 1-documented applicability in asymmetric synthesis, no fully detailed paper has been published so far, concerning the preparation and isolation of enantio- and diastereomerically pure (-)-8-phenylmenthol. ... 

Reductive amination reactions of keto acids are performed with amino acid dehydrogenases. NAD-dependent leucine dehydrogenase from Bacillus sp. is of interest for the synthesis of (S)-fert.-leucine [15-17]]. This chiral compound has found widespread application in asymmetric synthesis and as a building block of biologically active substances. The enzyme can also be used for the chemoenzy-matic preparation of (S)-hydroxy-valine [18] and unnatural hydrophobic bran-ched-chain (S)-amino acids. NAD-dependent L-phenylalanine dehydrogenase from Rhodococcus sp. [19] has been used for the synthesis of L-homophenyl-alanine ((S)-2-Amino-4-phenylbutanoic acid) [9]. These processes with water-soluble substrates and products demonstrate that the use of coenzymes must not... 

Diorganozinc reagents display an enhanced chemical reactivity compared to alkylzinc halides and furthermore, they are better suited for applications in asymmetric synthesis.38,39... 

Related Amino Alcohols and Their Applications in Asymmetric Synthesis.121... 

RELATED AMINO ALCOHOLS AND THEIR APPLICATIONS IN ASYMMETRIC SYNTHESIS... 

P. Knochel, New Preparations of Polyfunctional Dialkylzincs and Their Application in Asymmetric Synthesis, Chemtracts Organic Chemistry 1995, 8, 205. 

Y. L. Bennani, S. Hanessian, "Trans-]. 2-l)iammocyclohcxanc Derivatives as Chiral Reagents, Scaffolds, and Ligands for Catalysis Applications in Asymmetric Synthesis and Molecular Recognition, Chem. Rev. 1997, 97,3161-3195. 

Although N-amino derivatives of oxazolidinones were sporadically reported in the literature [41-43], no applications in asymmetric synthesis were known prior to our... 

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