Relative configuration, determination

In considering the retrosynthetic analysis of juvabione, two factors draw special attention to the bond between C(4) and C(7). First, this bond establishes the stereochemistry of the molecule. The C(4) and C(7) carbons are stereogenic centers and their relative configuration determines the diastereomeric structure. In a stereocontrolled synthesis, it is necessary to establish the desired stereochemistry at C(4) and C(7). The C(4)-C(7) bond also connects the side chain to the cyclohexene ring. As a cyclohexane derivative is a logical candidate for one key intermediate, the C(4)-C(7) bond is a potential bond disconnection. 

Nuclear Magnetic Resonance Method for Relative Configuration Determination... 

Figure 11. Molecular modeling of aeanthifolin based on the skeletal structure and relative configuration determined by NMR left top tube model right top ball-and-stick model bottom space-filling model (H white C black 0 gray).

Chemical conversion of compounds to intermediates of known absolute configuration is a method routinely used to determine absolute configuration (86). This is necessary because x-ray analysis is not always possible suitable crystals are required and deterrnination of the absolute configuration of many crystalline molecules caimot be done because of poor resolution. Such poor resolution is usually a function of either molecular instability or the complex nature of the molecule. For example, the relative configuration of the macroHde immunosuppressant FK-506 (105) (Fig. 8), which contains 14 stereocenters, was determined by x-ray crystallographic studies. However, the absolute configuration could only be elucidated by chemical degradation and isolation of L-pipecoUc acid (110) (80). 

Table 2.14 summarizes the steps by which molecular structures can be determined using the NMR methods discussed thus far to determine the skeleton structure, relative configuration and conformation of a specific compound. 

Since the olefmic CC double bond is trisubstituted, the relative configuration cannot be determined on the basis of the cis and trans couplings of vicinal alkene protons in the H NMR spectrum. What is the relative configuration given the C NMR spectra 19 ... 

The degradation of 2,6-xylenol (2,6-dimethylphenol) by bacteria produces a metabolite with elemental composition C8///0O2 as determined by high-resolution mass spectrometry Which carbon skeleton and which relative configuration are deducible from the NMR experiments 44, all obtained from one 1.5 mg sample ... 

Although no absolute configuration was known for any substance until the midtwentieth century, organic chemists had experimentally determined the configurations of thousands of compounds relative to one another (their relative configurations) through chemical interconversion. To illustrate, consider (-l-)-3-buten-2-ol. Hydrogenation of this compound yields (i-)-2-butanol. 

The two stereoisomeric furanose forms of D-erythrose ae naned a-D-erythro-furanose and p-D-erythrofuranose. The prefixes a and p describe the relative configuration of the anorneric cabon. The configuration of the anorneric cabon is cornpaed with that of the highest numbered chirality center in the molecule—the one that determines whether the cabohydrate is d or l. Chemists use a simplified, informal version of the lUPAC rules for assigning a and p that holds for ca bohydrates up to and including hexoses. 

The structure of the product is determined by comparison with a known compound26-27. The relative configurations of the other Mannich bases arc assigned tentatively, presuming that little variations should not be able to invert the stereochemical course of the reaction totally. f When the reaction is performed undeT reflux (10 min) the Mannich base anti-4 is obtained in 71 % yield. The minor diastereomcr syn-4 cannot be detected by H NMR. 

Addition of the anion of l-(diphenylphosphinyl)-2-octene to 4-/er/-butoxy-2-cyclopentenone occurs exclusively opposite to the rwr-butoxy moiety to give a mixture of. syn- and twr/ -adducls. As discussed above, the geometry of the alkcnc in the allylic moiety determines the relative configuration of the newly created stereogenic centers1. 

The 1,4-addition of the anion of a racemic /1-oxo sulfoxide to racemic 2-cyclopentenone was reported to give a single diastereomeric adduct resulting from addition opposite to the y-ace-toxy group20, t he relative configuration of the exocyclic stereocenter was not determined. 

In addition the corresponding (Z)-isomers were found, the relative configuration was not determined. 

Aroulanda, C., Boucard, V., Guibe, F., Courtieu, J., Merlet, D. Weakly oriented liquid-crystal NMR solvents as a general tool to determine relative configurations. Chemistry 2003, 9, 4536-4539. 

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