Chirality without chiral centres

The second type of compound is called an allene these compounds contain two double bonds involving the same carbon. These compounds exist, but are often difficult to prepare and are very reactive. It is the concept of chirality which is more important here than the chemistry of the compounds. If a carbon atom is 

The third example of chirality without a chiral centre is provided by spiro compounds, which we shall meet later when we consider the stereochemistry of polycyclic systems (see Section 3.5.1), but at this stage it is worth noting that they provide a third example of chirality 

However, it is also possible to visualize spiro compounds with groupings that are not aU different, where enantiomeric forms exist because mirror image compounds are not superimposable. The diamine shown is chiral, in that the mirror image forms are not superimposable, even though only two types of ring. 

The concept of torsional asymmetry is not jnst an interesting abstract idea. Some years ago, fertility in some Chinese rnral commnnities was found to be below normal levels, and this was traced back to the presence of gossypol in dietary cottonseed oil. Gossypol acts as a male contraceptive, altering sperm matnration, spermatozoid motility, and inactivation of sperm enzymes necessary for fertilization. Extensive trials in China have shown the antifertility effect is reversible after stopping the treatment, and it has potential, therefore, as a contraceptive for men. 

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A major trend in organic synthesis, however, is the move towards complex systems. It may happen that one needs to combine a steroid and a sugar molecule, a porphyrin and a carotenoid, a penicillin and a peptide. Also the specialists in a field have developed reactions and concepts that may, with or without modifications, be applied in other fields. If one needs to protect an amino group in a steroid, it is advisable not only to search the steroid literature but also to look into publications on peptide synthesis. In the synthesis of corrin chromophores with chiral centres, special knowledge of steroid, porphyrin, and alkaloid chemistry has been very helpful (R.B. Woodward, 1967 A. Eschenmoser, 1970). 

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. 

This is a member of an interesting class of compounds which are chiral, without actually containing a defined chiral centre. They are chiral because their mirror images are non-superimposable. In the case of this molecule, there is no rotation about the bond between the two naphthol rings because of the steric interaction between the two hydroxyl groups, d and T forms can be isolated and are perfectly stable (Optical purity determination by H NMR, D. R Reynolds, J. C. Hollerton and S. A. Richards, in Analytical Applications of Spectroscopy, edited by C. S. Creaser and A. M. C. Davies, 1988, p346). 

Cyclic ketene acetals, which have utility as co-polymers with functional groups capable of cross-linking, etc., have been prepared by the elimination of HX from 2-halomethyl-l,3-dioxolanes. Milder conditions are used under phase-transfer conditions, compared with traditional procedures, which require a strong base and high temperatures. Solid liquid elimination reactions frequently use potassium f-butoxide [27], but acceptable yields have been achieved with potassium hydroxide and without loss of any chiral centres. The added dimension of sonication reduces reaction times and improves the yields [28, 29]. Microwave irradiation has also been used in the synthesis of methyleneacetals and dithioacetals [30] and yields are superior to those obtained with sonofication. 

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. 

This is essentially the same as the tartaric acid example, without the conformational complication. Thus, there are two chiral centres, and the groups around each centre are the same. Again, we get only three stereoisomers rather than four, since the cis compound is an optically inactive meso compound. There is a plane of symmetry in this molecule, and it is easy to see that one chiral centre is mirrored by the other, so that we lose optical activity. 

Gossypol is a biphenyl system with ortho substituents, so there is restricted rotation about the bond joining the aromatic rings, creating torsional asymmetry and the existence of enantiomers without a chiral centre. We are only asked about the shape, and this will have the planar aromatic systems at right angles to minimize interaction between the ortho substituents. 

This type of chemistry has not been developed further into an efficient peptide synthesis involving A-terminal addition of amino acid residues to peptide esters. The main problems are concerned with the removal of the synthesized peptide from the cobalt(III) ion without causing racemization of chiral centres or hydrolysis of peptide linkages. 

Cram finished his synthesis by making and reducing the amide 6. Both steps go in excellent yield and, more importantly, without any racemisation as the chiral centre is not involved in either step. These principles are involved in all classical resolutions. 

In the crossed aldol reaction between acetaldehyde and propiophenone, two chirality centres are created and consequently, four stereoisomers will be produced. Compounds A and B are enantiomers of each other and can be described with the stereo descriptor u. Similarly, C and D are enantiomers and are /-configured. Since both starting materials are achiral, without the use of a chiral base or chiral auxiliary, racemates will be produced. Likewise the choice of base, the addition of a Lewis acid and the reaction conditions used to form the enolate can control which diastereomer is preferentially formed. If the Z enolate is formed, the u product is the preferred product, whilst the E enolate yields predominately the / product. 

Glycine is the only a amino acid without a chiral centre, but replacing one of the two protons on the central carbon with, say, deuterium creates one the CH2 carbon is prochiral. Similarly, converting malonate derivate into its monoesler makes a chiral centre where there was none the central C is prochiral. ... 

Revision of chirality without a chiral centre from Chapter 16 (pp. 398-9) and further exploration of pyridoxal reactions. 

Methylphenidate (MPH, Ritalin ) is a central nervous system stimulant that is used for the treatment of attention deficit disorders, with and without hyperactivity, and narcolepsy. MPH has two chiral centres and is marketed as a racemic mixture. It is known that d-threo-MP is pharmacologically more active than l-threo-MPH. The drag is rapidly metabohzed in humans to the inactive ritalinic acid. High-throughput analysis with chiral selectivity is demanded for the bioanalysis of MPH and its major metabolite. 

Compound 6, as with disubstituted allenes such as 4, illustrates the minimum requirements for chirality, but alkylidenecyclohexanes are known in which four different substituents occupy the key positions. Interestingly, the carboxylic acid 7 was the first example of this type of compound to be resolved into enantiomers, and this feat was achieved over 25 years before the resolution of an allene. One can, of course, consider other than six-membered rings in the context of chirality without stereogenic centres, and examples of alkylidenecyclobutanes are well documented (see Rossi and Diversi1 and Runge2). 

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