Optically active centres

These reactions follow first-order kinetics and proceed with racemisalion if the reaction site is an optically active centre. For alkyl halides nucleophilic substitution proceeds easily primary halides favour Sn2 mechanisms and tertiary halides favour S 1 mechanisms. Aryl halides undergo nucleophilic substitution with difficulty and sometimes involve aryne intermediates. 

In principle, all of the elements of the periodic table can be used to iucorporate foreign ions in crystals. Actually, only a number of elements have been used for optically active centres in crystals in other words, only a number of elements can be incorporated in ionic form and give rise to energy levels within the gap separated by optical energies. The most relevant centers for technological applications (although not the unique ones) are based on ions formed from the transition metal and rare earth series of the periodic table, so we will focus our attention on these centers. 

Natural optical activity is based on the structure of the molecules (optically active centres). Artificial optical rotation is found in magnetic fields the Faraday-Verdet effect or Magneto-Optic Effect, discovered by Michael Faraday in 1845. The theoretical basis for this effect was developed by James Clerk Maxwell in the 1860s and 1870s. From investigations on small molecules we know that the study of magneto-optical rotation offers interesting correlations with the chemical structure and that additive properties of the Verdet constant have been found. 

The carbohydrates also have a lot of OH groups, which means a lot of hydrogen bonding. Note also how many possible optically active centres (asymmetric carbon atoms) there are in the molecules. 

Rhoeagenine diol (228) has also served to confirm the structure of the alkaloid 14-demethoxyrhoeadine (230).227 Treatment of (228) with 2M-HC1 for 2 hours on the steam bath gave a quantitative yield of (230). Further evidence for structure (230) was obtained by exhaustive Hofmann methylation and spectroscopic studies. On the basis of comparison of optical rotations for rhoeadine (223 R1 = R4 = Me, R2 + R3 = CH2) and 14-demethoxyrhoeadine (230), the contribution of the optically active centre at C(14) in the former was determined to be [a]l2 +396° (chloroform).227... 

Other 1,4-Eliminations Fluoride ion induced desilylation is a very mild method that allows generation of heterocyclic o-quinodimethanes at ambient temperature and is suitable for inter- and intramolecular Diels-Alder adduct formation (Scheme 17). However, the presence of F can be a problem, leading to epimerisation of optically active centres <85CJC3526>. Long routes required for the synthesis of the silylated precursors and purification problems detract somewhat from this otherwise excellent method. 

The existence of exchange in such a way prompts the speculation that it may also occur with other molecules, but remain undetected because no optically active centre is present. 

Pantothenic acid has an optically active centre and only those compounds derived from the D-form possess vitamin activity. Since the free acid is unstable, only its salts, the corresponding alcohol, panthenol. 

Also due to the high barrier of inversion, optically active oxaziridines are stable and were prepared repeatedly. To avoid additional centres of asymmetry in the molecule, symmetrical ketones were used as starting materials and converted to oxaziridines by optically active peroxyacids via their ketimines (69CC1086, 69JCS(C)2648). In optically active oxaziridines, made from benzophenone, cyclohexanone and adamantanone, the order of magnitude of the inversion barriers was determined by racemization experiments and was found to be identical with former results of NMR study. Inversion barriers of 128-132 kJ moF were found in the A-isopropyl compounds of the ketones mentioned inversion barriers of the A-t-butyl compounds lie markedly lower (104-110 kJ moF ). Thus, the A-t-butyloxaziridine derived from adamantanone loses half of its chirality within 2.3 days at 20 C (73JCS(P2)1575). 

The occurrence of two optically active forms of each of the acids, lysergic and wolysergic, implies the existence in each of one centre of asymmetry (C ). 

Blauer G (1974) Optical Activity of Conjugated Proteins. 18 69-129 Bleijenberg KC (1980) Luminescence Properties of Uranate Centres in Solids. 42 97-128 Boca R, Breza M, Pelikan P (1989) Vibronic Interactions in the Stereochemistry of Metal Complexes 71 57-97... 

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. 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

Reaction of optically active a-sulphinyl acetate 298a with prochiral carbonyl compounds proceeds with a high asymmetric induction - , the degree of which depends on the nature of substituents at the carbonyl group (equation 252 Table 22) . The jS-hydroxy sulphoxides 422 formed may be transformed to optically active p-hydroxycarboxylic esters 423 (equation 253) and optically active long-chain lactones 424 99 (equation 254). Corey and coworkers have used this method to introduce a chiral centre at C-3 in their synthesis of maytansin °°, and Papageorgiou and Benezra for the synthesis of chiral a-hydroxyalkyl acrylates 425 ° (equation 255). 

Optically active drugs now occupy centre stage status and some agrochemicals like (S)-metolachlor, have also been introduced as optically pure isomers, so that the ballast of the unwanted isomer is avoided. Asymmetric synthesis is a topic of great interest in current research, and there is a steady flow of articles, reviews and books on almost every aspect of this subject. Table 4.8 lists examples of industrially important asymmetric synthesis. 

Optical activity in metal complexes may also arise either if one of the ligands bound to the metal in the first co-ordination sphere is itself optically active or if the complex as a whole lacks a centre of inversion and a plane of symmetry. Thus all octahedral cts-complexes of the tris-or bis-chelate type have two isomeric forms related by a mirror plane, the d- and /-forms. These species have circular dichroism spectra of identical intensities but opposite in sign. The bands in the circular dichroism spectrum are, of course, modified if ligand exchange occurs but they are also exceedingly sensitive to the environment beyond the first co-ordination sphere. This effect has been used to obtain association constants for ion-pair formation. There also exists the possibility that, if such compounds display anti-tumour activity, only one of the mirror isomers will be effective. 

Prototropic interconversions have been the subject of much detailed study, as they lend themselves particularly well to investigation by deuterium labelling, both in solvent and substrate, and by charting the stereochemical fate of optically active substrates having a chiral centre at the site of proton departure. Possible limiting mechanisms (cf. SNl/SN2) are those (a) in which proton removal and proton acceptance (from the solvent) are separate operations, and a carbanion intermediate is involved, i.e. an intermolecular pathway and (b) in which one and the same proton is transferred intramolecularly ... 

Enantiomer A single form of an optically active compound. Optically active compounds usually (but not exclusively) contain one or more chiral centres. Enantiomers are defined by their ability to rotate the plane of beam of polarised light one way or the other and these are referred to as either D or L , or alternatively + or, depending on whether the polarised light is rotated to the right (Dextro) or the left (Levo). 

This point of view finds its justification in the following observations. Compounds 8 (pyrocalciferol) and 9 (isopyrocalciferol), having opposite absolute configurations of the stereogenic centres near the dienes, show lA —> 1B Cotton effects at about 275 nm of the same sign and intensity. The reason for this is that only the twist of the chromophore determines the optical activity in fact the diene moieties are distorted in the same sense in 8 and 9, as found by X-ray diffraction16. 

Although the tin hydride reductions of alkyl halides seem simple, one must be careful because these reactions occur by a free radical mechanism. This is important, because the carbon radical produced in the reaction can isomerize68,78 and one often obtains two different stereoisomers from the synthesis. Another problem is that chiral centres can be lost in tin hydride reductions when an optically active halide is reduced. One example of this is the reduction of benzyl-6-isocyanopenicillanate with tributyltin deuteride78 (Scheme 14). The amount of isomerization depends on the temperature, the concentration of the tin hydride and the presence of and /-substituents78-82. However, some authors have reported tin hydride reductions where no racemization was observed78. 

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