Chiral compounds, Amino acids Epoxides

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Chiral homoallylamines are valuable intermediates for the preparation of compounds such as amines, P-amino acids, 1-amino-3,4-epoxides, and 1,3-amino alcohols.24 High 1,3-asymmetric induction has been achieved during the allylation of imines derived from chiral auxiliaries such as P-amino alcohols and a-amino acid esters.25 Drawbacks of these methods are the limited availability... 

Alder reactions, 1,3-dipolar cycloadditions (Jen et al. 2000), and conjugate additions of electron rich aromatic and heteroaromatic compounds can be catalyzed using chiral amino acid derived imidazolidinones as catalysts (Scheme 17 Eqs. 35-38 Paras and MacMillan 2001, 2002 Austin and MacMillan 2002 Brown et al. 2003b). In addition, highly enantioselective epoxidations (Marigo et al. 2005b) and cyclopropana-tions (Kunz and MacMillan 2005) have recently been developed. 

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... 

If the molecule is chiral, decide whether or not it is enantiomerically pure. You will often have to know more about the reaction than is evident in the scheme. For instance, fran.v-stilbene oxide 56 is always chiral but may or not be racemic. It is not evident in the scheme below and it could easily be either. It all depends how it was made. If only achiral starting materials and reagents were used, the epoxide 56 must be racemic. If asymmetry was present somewhere, it may be a single enantiomer. But had we put optically pure stilbene oxide 56 into the reaction then we could expect to get an optically pure product 57 at the end. Amino acid 54 is likely to be enantiomerically pure anyway (as are other compounds from the chiral pool) and if we were in any doubt it has been drawn as a single enantiomer. In other situations we need to know the context to be sure. 

The HIV protease inhibitor palinavir 13 (from Bio-Mega/Boehringer, Quebec) is a complex molecule that can be disconnected simply to five components. Two of these (14 and 18) are simple achiral aromatic compounds and two can be derived from the chiral pool (chapter 25) the amino acid valine 15 and an epoxide 16 derived from phenylalanine. The fifth 17 is the subject of this section. This compound has two chiral centres so we must first produce the right (syn-) diastereo-isomer and then the right enantiomer. 

Occasionally, a chiral diol can serve as host for one optical isomer (e.g., an epoxide), allowing the other one to be distilled out. The guest optical isomer can then be recovered by stronger heating. A quaternary ammonium salt, derived from the amino acid leucine, has been used to resolve 1,1 - bi-2-naphthol (7.4) by formation of an inclusion compound.57... 

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. 

In Chapter 7, we briefly mentioned that there were a number of biological methods for resolution of racemic mixtures of chiral compounds. Because enzymes, biological catalysts, are composed of chiral amino acids, they will generally accept only the natural enantiomer of a compound as their substrate. Some enzymes are very specific as to their substrate, but others can be used with whole classes of substrate, even where these are not very close in overall structure to their natural substrates. The simplest form of resolution involves a racemate, where one enantiomer is transformed by the enzyme and the other is not. This is called kinetic resolution, since it depends on the relative rates of enzymatic catalysis of the reactions of one enantiomer over the other. Our first example is shown in Figure 15.22. When the epoxide is opened by the Grignard reagent, only the tra s-product is formed, but this is a racemic mixture. The alcohol is converted to an ester, which is then hydrolyzed enzymatically using a lipase enzyme from Pseudomonas fluorescens. Notice the very mild conditions for... 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

Enantiopure organic compounds, which can easily be obtained from natural sources, e.g., D- and L-tartaric acid, D-mannitol, L-lactic acid, and L-amino acids, have served as precursors for chiral oxiranes through multistep syntheses. New chemical methods allowing for the desymmetrization of achiral epoxides have been reviewed recently [15]. 

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