Cis-Diastereomer

Turning to cyclic compounds we see that there are three not four stereoisomeric 1 2 dibromocyclopropanes Of these two are enantiomeric trans 1 2 dibromocyclo propanes The cis diastereomer is a meso form it has a plane of symmetry... 

The reaction is somewhat selective for the cis diastereomer. The use of chiral additives in this reaction leads to aziridines enantioselectively. 

The differential in chelation capacity between BF3 and SnCl4 was used to control the stereochemistry of the cyclization of the vinyl silane 10." With BF3, the reaction proceeds through a nonchelated TS and the stereochemistry at the new bond is trans. With SnCl4, a chelated TS leads to the cis diastereomer. 

Incubation % Radioactivity as (-)-cis and (-)-trans diastereomers % Radioactivity as (+)-cis diastereomer % Radioactivity as (+)-trans diastereomer... 

The lifetimes of the 9 main thymidine hydroperoxides 5-7 that were determined in pure aqueous solutions at 37 °C were found to vary from 1 h for the two trans diastereomers of 6-hydroperoxides (Table 1) to several weeks for 5-(hydroperoxymethyl)-2 -deoxyuridine. It may be added that the cis diastereomers are more stable than the trans homologues, irrespective of the pair of diastereomeric hydroperoxides. Interestingly, at neutral or slightly acidic pH values a specific hydrolytic decomposition pathway was observed for the two classes of hydroxyhydroperoxides. Thus, it was found that the trans and... 

Pulse radiolysis experiments have shown that "OH radical adds preferentially at C5 of the uracil moiety, giving rise to the reducing 5-hydroxy-5,6-uracil-6-yl radical. Interestingly, the two cis diastereomers of 6-hydroperoxy-5-hydroxy-5,6-dihydrouridine, two of the expected final products of the latter radicals in aerated aqueous solutions, have been prepared by trifluoroacetic acid treatment of uridine (3, R = H, = ribose) in the presence of H202 (equation 14). The mechanism of the reaction that involves transient formation of an epoxide-type intermediate followed by nucleophilic attack by a perhy-droxyl group at C6 presents similarities with the substitution of thymine bromohydrin by... 

Introduction of the C2 sulfonamide is accomplished via sulfonylation with chlorosulfonic acid, conversion to the sulfonyl chloride using thionyl chloride, and amidation using concentrated ammonium hydroxide in tetrahydrofuran. Reduction of the 4-acetamido compound using borane-tetrahydrofuran complex provides the 4-ethylamino derivative. The 45,65-frans diastereomer is selectively crystallized as its maleate salt from acetone in the presence of the unwanted 4R,6S-cis diastereomer. Neutralization of the maleate salt and extraction of the free base in ethyl acetate, followed by formation of the hydrochloride salt, yields crude dorzolamide hydrochloride. 

Several cyclodipeptides have been subjected to base-catalyzed epimerization (EtOH/NaOEt at 30-75°C) and the ratio of cis-to-trans isomers at equilibrium has been determined (74JA3985). The results have been correlated with the conformation of the molecules. Thus, cyclo(Pro-Pro) NMR studies (73JA6142) have indicated a boat form in the cis and a planar form in the trans diastereomer. In the latter, the pyrrolidine rings take up a half-chair conformation, which is greatly strained as long as the amide bonds are planar. This renders the trans less stable than the cis diastereomer. Consequently, at equilibrium, only cis diastereomer is found the trans isomer occurs to the extent of less than 0.5%. 

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)-... 

Rearrangement of (3-lactams, bearing a bromo-iso-alkyl group at C4, to y-lactams via A-acyliminium intermediates has been described by De Kimpe [142-144]. Besides the major trans y-lactam product 187 and 188, respectively, traces of the corresponding cis diastereomer and minor quantities of the dehydro-halogenated (3-lactam, are also obtained (Scheme 57). Application to the synthesis of bicyclic y-lactams from monocyclic (3-lactams has been described [144]. 

Cis diastereomer greater increase in crowding when carbon changes from sp2 to sp3 formed more slowly... 

Molecular mechanics calculations also led to an explanation of the diastereose-lective course of the reaction. Several assemblies of the imino ester, 44, and the zwitterionic enolate were investigated [52]. In accordance with the experimental results it was found that the assembly leading to the cis diastereomer was of lowest energy. Because the lowest-energy trans assembly is several kilocalories higher, or-ganocatalytic / -lactam formation proceeds with an excellent cis diastereoselectivity. 

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