Racemization cis isomers

The structure of the simple hydroxamate complex tris(benzohy-droxamato) iron (III) (R = , R = H in Figure 1) has shown the most stable crystalline form of the solid to be the racemic cis isomer (11). (The convention for symbols of absolute configurations A and A are those of the IUPAC Proposal (12). The cis isomer is defined as the isomer... 

Even though the activation energy of this process may be less than that for other paths, a low frequency factor would allow other paths to compete at higher temperatures. This postulate would also explain the temperature dependence of the Bailar inversions. An alternate, oriented ion-pair mechanism has been suggested previously (P, 26 6S) but the observations with [CoCl2(en)2] in methanol ( 21 make this less probable because both the ion pair and the solvated ion appear to give trans and racemic cis isomers under the conditions studied. Some orientation effects would be expected for the ion-pair reaction if it were operative in the inversion reactions. 

A mechanism for this reaction has been proposed [75], The first key intermediate in the reaction is the copper(I) acetylide 42. The additional ligand may be solvent or H2O. The acetylene moiety in 42 is activated for a 1,3-dipolar cycloaddition with the nitrone to give intermediate 43, with introduction of chirality in the product. A possible route to ris/traws-41 might be via intermediate 44. Finally, the cis isomer is isomerized into the thermally more stable trans-41. It should be mentioned that the mechanism outlined in Scheme 6.32 was originally proposed for a racemic version of the reaction to which water was added. 

Optically active hydroperoxides 244 were found285 to oxidize prochiral sulphides into the corresponding sulphoxides in higher optical yields (up to 27%) in comparison with those observed with peracids (equation 132). Moreover, the optical purity of the sulphoxides formed may be enhanced by addition of Ti(OPr-i)4. The oxidation of racemic 2-methyl-2,3-dihydrobenzothiophene 246 with these peroxides gave a mixture of cis and trans-sulphoxides 247 (equation 133). In all cases of the oxidation with the hydroperoxide alone the formation of the trans-isomer was strongly preferred and the e.e. value (up to 42%) of the cis-isomer was always higher than that of the trans-isomer. Moreover, the addition of Ti(OPr-i)4 furthermore promoted the selective formation of the frans-sulphoxide 247 and remarkably enhanced the e.e. value of both isomers. 

Development of new synthetic routes to optically active (3-lactam derivatives is still an attractive problem in organic chemistry. As a synthetic approach to penicillin derivatives, photocyclization of oe-oxoamides 76 to (3-lactams has long been studied 41, 42). This reaction (Scheme 6), however, results in a complex mixture of racemic cis-and trans-isomers of (3-lactams 72 and of oxazolidin-4-ones 73, since the reaction proceeds via a zwitterionic intermediate 7143>. Of these isomers, only the optically... 

Mislow and co-workers (258) and Hammond (259) have shown that optically active diaryl sulfoxides, which are configurationally stable in the dark at 200°C, lose their optical activity after 1 hr at room temperature on irradiation with ultraviolet light. Similarly, an easy conversion of the trans isomer of thianthrene-5,10-oxide 206a into the thermodynamically more stable cis isomer takes place upon irradiation in dioxane for 2 hr. However, the behavior of a-naphthylethyl p-tolyl sulfoxide under comparable irradiation conditions is different, namely, it is completely decomposed after 4 min. These differences are not surprising because the photochemical racemization of diaryl sulfoxides occurs by way of the pyramidal inversion mechanism whereas decomposition of the latter sulfoxide occurs via a radical mechanism with the cleavage of the sulfur-carbon bond. It is interesting to note that photoracemization may be a zero-order process in which the rate depends only on the intensity of the radiation and on the quantum yield. 

A second example of the use of ionic chiral auxiliaries for asymmetric synthesis is found in the work of Chong et al. on the cis.trans photoisomerization of certain cyclopropane derivatives [33]. Based on the report by Zimmerman and Flechtner [34] that achiral tmns,trans-2,3-diphenyl-l-benzoylcyclopropane (35a, Scheme 7) undergoes very efficient (0=0.94) photoisomerization in solution to afford the racemic cis,trans isomer 36a, the correspondingp-carboxylic acid 35b was synthesized and treated with a variety of optically pure amines to give salts of general structure 35c (CA=chiral auxiliary). Irradiation of crystals of these salts followed by diazomethane workup yielded methyl ester 36d, which was analyzed by chiral HPLC for enantiomeric excess. The results are summarized in Table 3. 

The crystal structure of five members of the ferrioxamine family has been determined ferrioxamine Di , ferrioxamine E °, desferrioxamine E , the retro-isomer of fer-richrome E and ferrioxamine B . While all of the Fe(III)-ferrioxamine structures (Table 2) crystallize as racemic mixtures of A- and A-cis isomers , the configuration of the binary ferrioxamine-B in EhuD complex (2.0 A resolution) is A-C-trans,cis, indicating that the interaction between ferrioxamine-B and FhuD is enantioselective, and also exhibils geomelric seleclivily. 

Since (Z)- and ( )-stereoisomers of unsaturated oxazolones can be obtained using appropriate isomerization procedures, cis and trans isomers of cyclopropane derivatives can be obtained in a stereoselective manner, although special care must be taken with experimental conditions to obtain the best stereoselectivity. Both racemic cis- and fraui-l-amino-2-phenylcyclopropanecarboxylic acid 641 and 644 have been obtained from the corresponding (Z)- or ( )-4-benzylidene-2-phenyl-5(4//)-oxazolone 621 and 642 using diazomethane. Care was taken to affect the... 

For the cis isomer, the ratio of racemization to epimerization was found to be 107 at 274.5 °C, and the cis isomer was found to undergo racemization 16.2 times faster than the trans isomer. The ratio of racemization to epimerization for the latter was found to be only 6.6 at 274.5 °C. Thus, these experiments confirmed the computational predictions that in 9b and 9c, double methylene rotations are faster than any process that leads to net single methylene rotation, and the preferred mode of double rotation is disrotation, rather than conrotation. ... 

Scheme 4.26 Lipase PS-catalyzed acylation for resolution of the racemic cis- and frans-isomers of 4-acetoxy-3-pentyltetrahydropyran (Jasmal).

Sertraline is the active pharmaceutical ingredient (API) in Pfizer s antidepressant Zoloft [25]. The developed commercial process employs an SMB chromatographic resolution of tetralone (Scheme 13.10) in >99% ee followed by diastereoselective reductive amination to give 95% sertraline (cis-isomer) and 5% trans-isomer the (4R)-tetralone can be racemized with an alkoxide base [8]. Asymmetric processes to sertraline have been described [26]. Our studies started with the original patented process involving palladium-catalyzed reductive amination of a tetralone to give a mixture of 80% racemic-cis and 20% racemic-trans diastereomers [27]. The cis-diastereomer can be purified by selective crystallization from toluene followed by diastereomeric crystallization of the (lS,4S)-enantiomer using (R)-... 

Explain how the stereoisomeric butadienes 4.120 and 4.121 equilibrate without forming any of the isomer 4.122. Similarly explain how the enantiomerically enriched rrans-2,3-di-t-butylcyclopropanone 4.123 racemizes at 80°, but does not form even a trace of the cis isomer 4.125. 

The basic principle of the stereochemistry of the hydrogenation of the C=C bond is syn (cis) addition. Established already in the early 1930s, it means that both hydrogen atoms add from the same face of the double bond. One of the highest selectivities was observed in the hydrogenation of isomeric 2,3-diphenyl-2-butenes144 the mesa compound is formed from the cis isomer in 98% yield (equation 8), whereas the trans isomer gives the racemic compound in 99% yield (equation 9). 

Data in Table 6 show accumulation of the trans isomers of 4-alky Icy clohexanols (47, 48 and 49) in the crystalline complexes.The same tendency in combination with partial resolution of trans-50 and trans-51 can be observed at 2-alkylcyclohexanols. [39] Furthermore, cis isomer content of the solid complexes remained racemic, consequently DBTA is selective resolving agent of trans-50 and trans-51. Efficiency of this isomer enrichment method is moderate, but it gives a very simple route to break up cis-trans and racemic compositions of the products obtained by nonselective synthesis. 

The transformation of tetrasubstituted ethylenes into 1,2,4-trioxolanes may also be achieved if the ozonolysis is carried out in the presence of a foreign carbonyl compound as described in Section 4.33.3.4. With formaldehyde as added carbonyl compound, 3,3-disubstituted derivatives are obtained, whereas in the presence of excess ketone (e.g. by using the latter as solvent), the ozonolysis gives rise to tetrasubstituted 1,2,4-trioxolanes which are difficult to prepare by other methods. Reactions (163) -> (164) and (165) -> (166) provide two examples of this versatile 1,2,4-trioxolane synthesis. Unlike the parent system (2), alkyl- and/or aryl-substituted 1,2,4-trioxolanes generally are stable, non-explosive compounds. Mixtures of crossed ozonides (cf. Section 4.33.3.1.1) or of cis and trans isomers can be separated by thin layer, column or gas chromatography. The cis isomers of symmetrical 3,5-disubstituted 1,2,4-trioxolanes are meso forms, whereas the corresponding trans isomers represent racemates which in some cases have been resolved into their optical... 

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