Optically active products stereoselective synthesis

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

Photolysis of solutions of C6o(OH)ig at low solute concentration leads to [C6o(OH)i8] by electron transfer from Me2C(OH) radicals or from hydrated electrons, and this has enabled the reduction potential of the C6o(OH)ig/ [C6o(OH)ig] couple to be estimated. The kinetics of the photoreduction of hexanal using RhCl(PMe3)2CO as catalyst have been measured and the feasibility of a photocatalytic synthesis of hexanol from pentane, CO, and H2 in the presence of rhodium complexes has been demonstrated. Irradiation of a chiral bimolecular crystal of acridine and R-(-)- or S-(+)-2-phenylpropionic acid induces photodecarboxylation followed by stereoselective condensation to give a mixture of three optically active products, and the 3-0-S-methyl dithiocarbo-nate derivatives of oleanolic and ursolic methyl esters have been used as models for the photodeoxygenation of alcohols. ... 

Rahman and Fraser-Reid used a sugar-based approach for their synthesis of actinobolin [12], and hence an optically active product was assured. Therefore the challenge, as with the use of L-threonine in Sects. 1.3 and 1.4, was to make the most efficient use of the chiron [27]. In this context, efficiency can be equated with stereoselectivity, and as such, it is the direct outcome of synthetic design. 

A possible way to induce selectivity in the photodecarboxylation process could be through photosensitized reactions in the soHd state. In fact, when a two-component molecular crystal of phenanthridine and 3-indoleacetic acid is irradiated at low temperature (-70°C), 3-methyHndole is formed in high yield as the sole product by contrast, when the same reaction is carried out in acetonitrile solution, four products are obtained.Furthermore, irradiation of two-component molecular crystals of arylalkyl carboxylic acids with stoichiometric amounts of electron acceptor causes decarboxylative condensation between the two components with important selectivities. " Thus, irradiation of (S)-naproxen in a chiral crystal with 1,2,4,5-tetracyanobenzene produces a decarboxylated condensation product retaining the initial chirality." Photolysis of an enantiomorphous bimolecular crystal of acridine with the R or S enantiomer of 2-phenylpropionic acid causes stereoselective condensation to give three optically active products. An absolute asymmetric synthesis has also been achieved by the enantioselective decarboxylative condensation of a chiral molecular crystal formed from achiral diphenylacetic acid and acridine (Scheme 9). ... 

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

An excellent method for the diastereoselective synthesis of substituted amino acids is based on optically active bislactim ethers of cyclodipeptides as Michael donors (Schollkopf method, see Section 1.5.2.4.2.2.4.). Thus, the lithium enolates of bislactim ethers, from amino acids add in a 1,4-fashion to various a,/i-unsaturated esters with high diastereofacial selectivity (syn/anti ratios > 99.3 0.7-99.5 0.5). For example, the enolate of the lactim ether derivative 6, prepared from (S)-valine and glycine, adds in a highly stereoselective manner to methyl ( )-3-phenyl-propenoate a cis/trans ratio of 99.6 0.4 and a syn/anti ratio of 91 9, with respect to the two new stereogenic centers, in the product 7 are found105, los. 

RhH(PPh3)4 (1 mol%) exhibited higher catalytic activity and promoted a complete reversal in stereoselectivity to provide the trans isomer of 24 and 25 as the major reaction product. The czs-cyclopentane 29, derived from optically active 28, was converted to the differentially protected cyclopentane triol 29, which, in turn, converted to the differentially protected tetrad 30, a key intermediate in the synthesis of enantiopure bioactive carbo-cyclic nucleosides [19]. 

The chiral lactone alcohol derivative (178)181) can be readily prepared from natural (S)-glutamic acid, the cheapest chiral a-amino acid. Lactone (178) was alkylated to yield optically active 3-substituted lactone alcohol derivatives, (179) and (180), which were intermediates in the stereoselective synthesis of various natural products 182). 

Spiroannulations with diphenylsulfonium cyclopropanide have also been performed with polycyclic systems. Optically active 4-methyladamantan-2-one (21b),7 and the all-ds configurated tetraquinanes 23,72 73 and 2574 reacted stereoselectively with formation of syn- and endo,enclo-configurated cyclobutanones 22b, 24 and 26, respectively. The last two products 24 and 26 have been further elaborated in a successful75 and a prospective74 synthesis of dodecahcdrane. 

Asymmetric intramolecular Wittig reaction. Trost and Curran2 have examined eight readily available optically active phosphines in a stereoselective synthesis of the ilikctone (2), a useful intermediate to several natural products. Of these, CAMP is dearly the most efficient phosphine for this purpose (equation I). 

The extent of stereoselectivity in the chiral synthesis can be checked by determining the enantiomeric excess of the optically active olefins in the products. The optical purity was determined by gas chromatographic resolution of enantiomers by means of an optically active column. Thermostable substituted cyclodextrins are well suited as asymmetric phases (206). The trimer, 2,4-dimethyl-l-heptene, was resolved into its enantiomers by capillary gas chromatography with an octakis(6-0-methyl-2,3-r/-0-pentyl-)-7-cyclodextrine phase. 

The synthesis of optically active selenium-containing reagents as well as their application to stereoselective synthesis is of high current interest. Several products also contain a selenium functionality and their use as chiral ligands and catalysts in asymmetric reaction is promising. Various reactions of this type are known and some recent developments in this novel area are summarized here. 

In principle, three approaches may be adopted for obtaining an enantio-merically pure compound. These are resolution of a racemic mixture, stereoselective synthesis starting from a chiral building block, and conversion of a prochiral substrate into a chiral product by asymmetric catalysis. The last approach, since it is catalytic, means an amplification of chirality that is, one molecule of a chiral catalyst produces several hundred or a thousand molecules of the chiral product from a starting material that is optically inactive In the past two decades this strategy has proved to be extremely useful for the commercial manufacture of a number of intermediates for biologically active compounds. A few recent examples are given in Table 9.1. 

Tatsui G (1928) Synthesis of carboline derivatives. J Pharm Soc Jpn 48 453 159 Taylor MS, Jacobsen EN (2004) Highly enantioselective catalytic acyl-pictet-spengler reactions. J Am Chem Soc 126 10558-10559 Terada M, Uraguchi D, Sorimachi K, Shimizu H (2005) Process for production of optically active amines by stereoselective nucleophilic addition reaction of imines with C nucleophiles using chiral phosphoric acid derivative. PCT Int Appl WO 2005070875 2005-08-04... 

For complexes of type 10 (with a hydrogen at the carbene carbon) a synthesis was worked out in which a formamide is first reacted with K2[Cr(CO)j] followed by reaction with TMSCI [7]. This way, the non-racemic formamide 12 leads to the chirally modified amino carbene complex 13, which serves as starting material for the diastereoselective synthesis of various optically active yff-lactams [8]. An example is the (formal) total synthesis of 1-carbacephalothin 16, a carbon analog of the cephalosporins (Scheme 5) [8b]. In this case, the complex 13 is irradiated in the presence of in situ prepared imine 14 to afford the /(-lactam with high dia-stereoselectivity but only in modest yield. The product (15) could (in principle) be converted in to the target compound 16. 

Changing the transition-metal from palladium to rhodium (equation 62) makes possible, in addition to the straight-chain alkylation product (243), the regio- and stereoselective synthesis of amino acid derivatives with a terminal double bond (242), starting from optically active branched allylic substrates 241 (Table 21)" . Remarkably, the substitution products were obtained with high enantiomeric excesses, what might result from a slow isomerization of the intermediary formed allyl rhodium complexes ". 

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