Diastereomer derivatives reaction conditions

The validity of the model was demonstrated by reacting 35 under the same reaction conditions as expected, only one diastereoisomer 41 was formed, the structure of which was confirmed by X-ray analysis. When the vinylation was carried out on the isothiazolinone 42 followed by oxidation to 40, the dimeric compound 43 was obtained, showing that the endo-anti transition state is the preferred one. To confirm the result, the vinyl derivative 42 was oxidized and the intermediate 40 trapped in situ with N-phenylmaleimide. The reaction appeared to be completely diastereoselective and a single diastereomer endo-anti 44 was obtained. In addition, calculations modelling the reactivity of the dienes indicated that the stereochemistry of the cycloaddition may be altered by variation of the reaction solvent. 

The aforementioned observations have significant mechanistic implications. As illustrated in Eqs. 6.2—6.4, in the chemistry of zirconocene—alkene complexes derived from longer chain alkylmagnesium halides, several additional selectivity issues present themselves. (1) The derived transition metal—alkene complex can exist in two diastereomeric forms, exemplified in Eqs. 6.2 and 6.3 by (R)-8 anti and syn reaction through these stereoisomeric complexes can lead to the formation of different product diastereomers (compare Eqs. 6.2 and 6.3, or Eqs. 6.3 and 6.4). The data in Table 6.2 indicate that the mode of addition shown in Eq. 6.2 is preferred. (2) As illustrated in Eqs. 6.3 and 6.4, the carbomagnesation process can afford either the n-alkyl or the branched product. Alkene substrate insertion from the more substituted front of the zirconocene—alkene system affords the branched isomer (Eq. 6.3), whereas reaction from the less substituted end of the (ebthi)Zr—alkene system leads to the formation of the straight-chain product (Eq. 6.4). The results shown in Table 6.2 indicate that, depending on the reaction conditions, products derived from the two isomeric metallacyclopentane formations can be formed competitively. 

ABSTRACT The acid-catalysed epimerization reaction of bioactive indole alkaloids and their derivatives is reviewed. The three mechanisms, which have been proposed for the (J-carboline-type indole alkaloids, are discussed. Through recent developments, evidence for all three mechanisms has been obtained, which shows the complexity of the epimerization reaction. The epimerization seems to depend on structural features and reaction conditions making it difficult to define one universal mechanism. On the other hand, the isomerization mechanism of oxindole alkaloids has been widely accepted. The acid-catalysed epimerization reaction provides a powerful tool in selectively manipulating the stereochemistry at the epimeric centre and it can also have a marked effect on the pharmacology of any epimerizable compound. Therefore, examples of this reaction in die total synthesis of indole alkaloids are given and pharmacological activities of some C-3 epimeric diastereomers are compared. Finally, literature examples of acid-catalysed epimerization reactions are presented. 

Staudinger reaction of imine 8 derived from 7-oxanorbomenone with 2-alkoxy-acetyl chlorides in the presence of Et3N (toluene, RT), afforded (3-lactams 9 (Scheme 3). These were obtained as single diastereomers, and no traces of the corresponding isomeric exo-(3-lactams were detected in the crude reaction products [50]. It is worth mentioning that this stereochemical outcome of (3-lactam formation with acid chlorides under Staudinger reaction conditions was opposite to the one expected from a simple [2+2]-cycloaddition reaction, which should have taken place from the exo face of compound 8. 

General reaction conditions IMes HCI (0.05 mmol), DBU (0.05 mmol), THF (2.5 ml), cinnamaldehyde derivative (0.5 mmol), ketone (1.0 mmol), 16 h at rt. Yield given for the isolated mixture of diastereomers b Determined by GC-MS... 

As a final illustration, an unprecedented approach was discovered, wherein an in situ aza-Michael reaction was used that allowed the development of bridged tetrahydroquinoline-based tricyclic architectures under very mild reaction conditions [30]. In a typical example, enantio-enriched compound 52 (Figure 17.12) was converted to 53 in a series of steps. Following the acetonide and the N-Alloc removal, to our surprise there was no sign of the free amine derivative 54. Instead, compound 55 was obtained as single diastereomer. Under these mild reaction conditions, the in situ aza-Michael cyclization produced the bridged architectures. 

Using insights deriving from the studies of double asymmetric reactions summarized in Eqs. (11.40)-(11.43), Marshall demonstrated that with judicious choice of reaction conditions, one can obtain all four possible diastereomers selectively... 

J23-22-Acetoxycholcstcrol derivatives can be converted stereoselectively with bis(aceto-nitrile)dichloropalladium(II) as a catalyst to 24-hydroxycholesterol derivatives435. The (225,23 )- and (225,23Z)-diastereomers react more rapidly than the (22i ,23 >isomer, and the (22i ,23Z)-compound does not rearrange under the reaction conditions. The difference in the reactivity is attributed to the different conformations of the side chains of the 22-hydroxy-cholesterol derivatives, as the coordination of the palladium complex with the 7t-electrons of the double bond from the side opposite the acetoxy group is sterically hindered in the less reactive derivative. 

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