Optically active compound synthesis cyclopropanes

The (ri" -diene tricarbonyliron)-substituted diazocarbonyl compounds 25 have been found to undergo 1,3-dipolar cycloaddition with methyl acrylate in high yield, but with little or no diastereoselectivity (56). Nevertheless, the facile chromatographic separation of the diastereomeric products 26a,b and 27a,b (Scheme 8.8), permits the synthesis of pure enantiomers when optically active diazo compounds (25) [enantiomeric excess (ee) >96%] are employed. When the reaction of 25 (R = C02Et) with methyl acrylate was carried out at 70 °C, cyclopropanes instead of A -pyrazolines were formed. The enantiomerically pure... 

These complexes can be isolated in some cases in others they are generated in situ from appropriate precursers, of which diazo compounds are among the most important. These compounds, including CH2N2 and others, react with metals or metal salts (copper, palladium, and rhodium are most commonly used) to give the carbene complexes that add CRR to double bonds.1063 Optically active complexes have been used for enantioselective cyclopropane synthesis.1064... 

Brunner et al. reported core-functionalised dendrimer metal catalysts ("dendri-zyme ) for use in enantioselective catalysis [lb, 10, 11]. Optically active dendrimer ligands were used, for example for the reaction of styrene with ethyl diazoacetate in a Cu(I)-catalysed enantioselective cyclopropanation. The starting compound for the preparation of these ligands was L-aspartic acid. However, (IS,2 S)-2-amino-1-phenyl-1,3-propanol can also serve as reactant for the synthesis of optically active dendrimer ligands. 

Preparative Methods substituted 2,3-methanoamino acids are difficult to prepare. Unfortunately, most of the reported syntheses give racemic materials whereas stereochemically pure compounds are required for studies of cyclopropane-based peptidomimetics. The only 2,3-methanologs of protein amino acids prepared in optically active form are ( )- and (Z)-cyclo-Phe and -Tyr, all four stereoisomers of cyc/o-Met, (Z)-cyclo-Arg and (25,35)-(Z)-cyc/o-Trp, although several routes to enantio-enriched 2,3-methanologs of simple nonproteogenic amino acids have been reported. " The most practical synthesis of the title compound is that based on a diastereoselective, rhodium-catalyzed cyclopropanation reaction. ... 

For the more reactive allylic halides 4 a and 4 b the salt of diethyl hydrazinodicarboxylate was used as the nucleophile in preference to hydrazine.Deazetization of the resultant 4,5-dihydro-37/-pyrazoles 5 gave a mixture of alkylidenecyclopropanes 6 and 7. It should be noted that attempts to make 4-isopropylidene-4,5-dihydro-37/-pyrazole (5 b) by the more obvious route (by the reaction of diazomethane with 3-methylbuta-l,2-diene) failed. This route has been modified for the synthesis of various deuterated derivatives of 5 and used to make optically active (3/ ,57 )-3,5-dimethyl-4-methylene-4,5-dihydro-3/f-pyrazole, but all of the cyclopropanes produced from thermolysis of this compound were racemic. A similar route has also been used in the synthesis of 7,7-dimethyl-6b,7a-dihydro-7//-cycIopropa[fl]acenaph-thylene. ... 

The diazo reaction with olefins as shown previously is still the fastest method to get hold of mixtures of diastereomers, often, however, with moderate yields due to the lack of reactivity of the olefins. Several nor-chrysanthemic esters [479], alkoxycyclopro-pane carboxylic esters [480,481], which are interesting because of their photostabihty and insecticidal activity [482], and 2,2,3,3-tetramethylcarboxyhc ester [483] were prepared by this route. Asymmetric synthesis using optically active iron carbonyl-olefin complexes afforded 1-R-configurated esters, i.e. precursors for caronaldehyde [484]. The addition of diazopropane across the double bond of olefinic esters via pyrazolines [485, 486] also provides a rapid access to sometimes more complex cyclopropane carboxylic esters with questionable purity, from which the pure compounds can be separated. 

In contrast to the aforementioned diazoalkanes and aryldiazomethanes, whose instability and high explosiveness have diminished their general utility as a monomer for polymer synthesis, diazocarbonyl compounds have been known to be rather stable and frequently used as a reagent for organic synthesis [35, 36], In particular, transition metal catalyzed cyclopropanation of diazocarbonyl compounds with C=C double bonds has been extensively investigated and established as a very useful method for the formation of cyclopropane frameworks, where application for asymmetric synthesis using various optically active ligands has been successfully achieved. 

Halogenated ligands were also employed in the asymmetric cyclopropanation reaction. For example, a rhodium complex with brominated TTL ligand 185 promoted the chiral synthesis of cyclopropanes from active methylene compounds in the presence of iodosylbenzene (Scheme 1.86) [132]. Cyclopropanes 186 were obtained in good optical purity. 

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