The Chiral Centre

A carbon atom to which four different groups are attached is known as a chiral centre. [Quite often it is also termed as chiral carbon, so as to make a clear cut distinction from chiral nitrogen, chiral phosphorus etc.]. 

Salient Features. There are a few salient features of a chiral centre, namely  

Explanation. A meso compound is one whose molecules are superimposable on their corresponding mirror images even though they contain chiral centres. Thus, a meso compound is optically inactive by virtue of the fact that the molecules are achiral the rotation caused by one molecule is cancelled by an equal and opposite rotation afforded by another molecule which is the mirror image of the first, as shown below  

3-Dichlorobutane Mirror images superimposable (A meso compound) 

Note Such achiral molecTiles invariably possess more than one chiral centre. In case, a molecule contains 

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Groups attached to the chiral centre are given an order of priority according to the sequence rules. For an enantiomeric carbon compound the group of lowest priority is... 

Proton-catalyzed olefin cyclizations of open-chain educts may give tri- or tetracyclic products but low yields are typical (E.E. van Tamelen, 1968, 1977 see p. 91). More useful are cyclizations of monocyclic educts with appropriate side-chains. The chiral centre to which the chain is attached may direct the steric course of the cyclization, and several asymmetric centres may be formed stereoselectively since the cyclizations usually lead to traas-fused rings. 

The ending caine stems from cocaine, the first clinically employed local anaesthetic. Procaine and tetracaine are ester-linked substances, the others are amides. Amide bonded local anaesthetics usually contain two i s in their name, ester-bonded only one. In the structure drawings, the lipophilic portion of the molecule is depicted at the left, the amine at the right. The asterisk marks the chiral centre of the stereoisomeric drugs. Lipid solubility is given as the logarithm of the water octanol partition coefficient, log(P). 

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). 

From a geometrical point of view, it is evident that all molecules having an aU-trans conformation in the alkyl chain close to the chiral centre (see mark in... 

Answer The required disconnection is (13a) which clearly needs optically active epoxide (15). This must be made from (14) without inverting the chiral centre so reduction of the COgEt group and conversion to a leaving group are needed. 

Example Optically active acid (16) was needed (p T 107 ) for the synthesis of an ant alarm pheromone. The branch point ( in 16) is also the chiral centre so it is better to avoid disconnections there. The 1,2 C-C disconnection (16a) is ideal as it gives synthon (17), for which we use a malonate ester, and halide (18), available from optically active alcohol (19), a major by-product from fermentation. 

Optically active ketone (6) was needed for a study of asymmetric induction It could be made from acid (7) by a Friedel Crafts route or from nitrile (8) by Grignard addition, but neither of these compounds could be made by alkylation as the branchpoint is on the 3 carbon ( in each). The 1,3 C-C disconnection, e.g. (6b) is not good as it destroys the chiral centre. 

The chiral centre first appears in cyanide (11) but the acid (10) is the ideal compound for resolution as it can form a salt with a naturally-occurring optically active base. 

The per acid first adds to the ketone to give adduct (30) which rearranges via a transition state (31) which is electron-deficient around the former carbonyl group. Consequently,the group which can best supply electrons to combat the deficiency migrates best. It does so with retention as it is a one step reaction in which the chiral centre ( in 30) never becomes detached. 

As far as I am aware, neither of these compounds has been synthesised. Can you devise routes Stereochemical control is essential lor (69) but the chiral centre to which the vinyl group is attached in (68) is unimportant as both epimers are natural products. 

As before, the chiral centre renders Ha and Hb non-equivalent and for the reasons already covered, Hx will couple to both with all three couplings (Ha-Hb, Ha-Hx and Hb-Hx) likely to be different. So the classical presentation of an ABX system is that of three multiplets, each of four lines. (Note that in Spectrum 6.2, the size of the Ha-X and the Hb-X couplings are almost identical so the X proton appears as an approximate triplet. This is quite common.). The AB part indicates that the geminal pair are likely to be relatively close in terms of chemical shift, whilst the X proton is someway distant from both. Obviously, the scope for variation in the appearance of ABX systems is enormous. The difference in chemical shift between Ha and Hb is a major factor in this but we have also come across ABX systems... 

Differences in the spectra of diastereoisomers are generally most noticeable in the region of the chiral centres. Spectrum 6.4 shows a typical example. 

The use of TFAE is demonstrated in Spectrum 7.4, which shows the appearance of proton b , before and after the addition of 30 mg of (+)TFAE to the solution. (This is the region of interest - it is usually protons nearest the chiral centre, which show the greatest difference in chemical shifts in the pair of... 

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 ... 

One of the most widespread theories is the theory of enolisation mechanism put forward by Beckmans in the last century and explains beautifully racemisation in compounds containing a carbonyl group next to the chiral centre ... 

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. 

Chiral centres encountered in anaesthetics usually have carbon or quaternary nitrogen as the chiral centre. Any compound which contains more than one chiral centre is termed a diastereoisomer by definition. 

The conformational kinetic control of the chiral centres present in a molecule may be exemplified by the rran -diaxial opening of an epoxide i rf a polycyclic system [7]. In this case, the less stable conformation is also "frozen" by forming an auxiliary lactone bridge, which reverses temporarily the conformations of the rings and the substituents. 

In all the examples commented upon so far, we have dealt with reactions with internal diastereoselective induction. However, when a chiral centre is already present in one of the components [12] we must refer then to a relative diastereoselective induction, and Cram s rule [13] must be taken into account when the chiral centre is present at the a-position of the aldehyde (28). For instance, in the reaction shown in Scheme 9.7 of the four possible diastereomers only two are formed, the Cram-i yn-aldol 30a being the predominant diastereomer (see below 9.3.3). 

Having established the origin of the rotamers Gl, G2 and G3, the splitting within each of these groups into further components due to the chiral centres in the amide side-chains was to be examined. These polyhydroxylated side-chains contain solely the threo (RS) form of 3-amino-butane-1,2,4-triol as a racemate (Fig. 19). Accordingly, from the possible 8 chiral centres only 4 have to be taken into consideration. These would lead - without considering other types of isomerism - to 16 isomers (8 pairs of isomers). Including (E)I(Z) isomerism, 48 isomers can be expected. 

These observations may refiect the proximity of the chiral centre to the part of the molecule that binds with the receptor site. 

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