Chiral centres configuration

Meso compound A symmetrical compound containing two chiral centres configured so that the chirality of one of the centres is equal and opposite to the other. Such internal compensation means that these compounds have no overall effect on polarised light (e.g., meso tartaric acid). 

The R, S convention is a scheme which has largely superseded the D, i. system to denote configuration about a chiral centre in a molecule. The convention allows unequivocal designation of the absolute configuration in a description of the positions in space of ligands attached to a chiral centre, in relation to an agreed standard of chirality like a right-hand helix. 

The achiral triene chain of (a//-rrans-)-3-demethyl-famesic ester as well as its (6-cis-)-isoiner cyclize in the presence of acids to give the decalol derivative with four chirai centres whose relative configuration is well defined (P.A. Stadler, 1957 A. Escherunoser, 1959 W.S. Johnson, 1968, 1976). A monocyclic diene is formed as an intermediate (G. Stork, 1955). With more complicated 1,5-polyenes, such as squalene, oily mixtures of various cycliz-ation products are obtained. The 18,19-glycol of squalene 2,3-oxide, however, cyclized in modest yield with picric acid catalysis to give a complex tetracyclic natural product with nine chiral centres. Picric acid acts as a protic acid of medium strength whose conjugated base is non-nucleophilic. Such acids activate oxygen functions selectively (K.B. Sharpless, 1970). 

The absolute configuration of any chiral centre can be unambiguously specified using the RS notation. 

Note. In cyclic forms of sugars, the configuration at the anomeric chiral centre is defined in relation to the anomeric reference atom (see 2-Carb-6.2). 

If sequences of chiral centres are separated by non-chiral centres, the non-chiral centres are ignored, and the remaining set of chiral centres is assigned the appropriate configurational prefix (for four centres or less) or prefixes (for more than four centres). 

If the carbonyl group(s) divides the sequence of chiral centres, the configurational prefixes are assigned in the normal manner (see 2-Carb-8.4) for all chiral centres the non-chiral centres are ignored. 

If the CH2 group divides the chiral centres into two sets, it is ignored for the purpose of assigning a configurational prefix the prefix(es) assigned should cover the entire sequence of chiral centres (see 2-Carb-8.4). 

Asymmetric conjugate addition of dialkyl or diaryl zincs for the formation of all carbon quaternary chiral centres was demonstrated by the combination of the chiral 123 and Cu(OTf)2-C H (2.5 mol% each component). Yields of 94-98% and ee of up to 93% were observed in some cases. Interestingly, the reactions with dialkyl zincs proceed in the opposite enantioselective sense to the ones with diaryl zincs, which has been rationalised by coordination of the opposite enantiofaces of the prochiral enone in the alkyl- and aryl-cuprate intermediates, which precedes the C-C bond formation, and determines the configuration of the product. The copper enolate intermediates can also be trapped by TMS triflate or triflic anhydride giving directly the versatile chiral enolsilanes or enoltriflates that can be used in further transformations (Scheme 2.30) [110],... 

As the absolute configuration of the asymmetric carbon atom is known to be S, it can be concluded from the relative configuration 56) of both chiral centres that (82)B is the S,S-isomer. As far as we know, this is the first absolute configuration... 

Enantiomer One stereo-structure around a chiral centre - the left- or right-hand configuration of a molecule. 

These compounds show typical s+rans-1,3-butadiene absorption bands between 230 and 235 nm, with emax 30000. In correspondence, the CD spectra show an intense (Ae 3-5) Cotton effect, positive for the (S) absolute configuration of the chiral centres. It is noteworthy that if one considered (E)-(S)-6 as a half of (E, E)-(3S,8S)-7 a value of Ae of about 0.4 would be predicted the actual Ae of +3 is one order of magnitude larger ... 

The absolute configuration of primary amines containing the chiral centre at the a-position has been correlated with the relative H shifts (upheld or downfield) observed in the NMR spectra of the amides formed with (5 )-0-methylmandelic acid, PhCH(0Me)C02H316. 

The two co-ordination sites, however, are equivalent due to the C2 symmetry of the diphosphine complex. This reduces the number of diastereomers from four to two. In Figure 4.5 the two enantiomeric intermediate alkene adducts have been drawn. Note that the faces are indicated by si, si and re, re because the configurations of two carbon atoms have to be assigned. After hydrogenation, only one chiral centre has formed at the a-carbon atom, because the (3-carbon atom now carries two hydrogen atoms and thus does not form a chiral centre. 

Now, if we allow one enantiomer of the chiral aldehyde 59 to react with the two enantiomers of the chiral enolate M, in one case the two chiral reagents will both promote the same absolute configuration at the two new chiral centres (65a ). However, no such effect will be observed in the other possible combination (c/. 65) (Scheme 9.21). In the first case, the effective "Cram s rule selectivity" shown by the aldehyde will be greater than in its reactions with achiral enolates. For the selectivities chosen the "Cram anti-Cram ratio" should be in our example of the order of 100 1 (see below 9.3.4., Masamune s "double asymmetric induction"). 

Caryophyllenes, as an example of two naturally occurring isomeric sesquiterpenes containing a medium-sized ring, in which the success of the total syntheses lies in the stereoselective control of a chiral centre, in a common synthetic key intermediate, which governs the configuration (JE or Z) of the double bonds present in each one of the two isomers. In this context, a brief reference to Cecropia Juvenile Hormone synthesis by the Syntex group, as well as to Johnson s cationic cyclisation of unsaturated polyolefins to fused polycyclic compounds, is made. 

Swainsonine is a trihydroxylated bicyclic indolizidine alkaloid with four chiral centres, whose relative stereochemistry was determined by X-ray crystallographic analysis and the absolute configuration was deduced on the basis of biosynthetic and asymmetric induction studies, and then confirmed by an enantiospecific synthesis from D-mannose [2a]. 

Let us look at the common substracture of the penicillin antibiotics, namely 6-aminopenicillanic acid, to illustrate some aspects of working out whether a chiral centre is allocated the I or 6 configuration. 

Configurational isomers with several chiral centres... 

Configurational isomerism involving one chiral centre provides two different structures, the two enantiomers. If a structure has more than one chiral centre, then there exist two ways of arranging the groups around each chiral centre. Thus, with n chiral centres in a molecule, there will be a maximum number of 2" configurational isomers. Sometimes, as we shall see in Section 3.4.5, there are less. 

Now the other three of the possible four stereoisomers are the (15,25), (l/f,2/f), and (15,2/f) versions. These are also shown, and mirror image relationships are emphasized. The (15,2/f) isomer is the mirror image of (—)-ephedrine, which has the (l/f,25) configuration. Therefore, it is the enantiomer of (—)-ephedrine, and can be designated (+)-ephedrine. Note that the enantiomeric form has the opposite configuration at both chiral centres. 

The other two isomers are the (15,25) and (IR,2R) isomers, and these two also share a mirror image relationship, have the opposite configuration at both chiral centres, and are, therefore, a pair of enantiomers. From a structure with two chiral centres, we thus have four stereoisomers that consist of two pairs of enantiomers. Stereoisomers that are not enantiomers we term diastereoisomers, or sometimes diastereomers. Thus, the (15,25) and (1R,2R) isomers are diastereoisomers of the (l/f,25) isomer. Other enantiomeric or diastere-omeric relationships between the various isomers are indicated in the figure. 

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