Achiral compounds

Our journey begins with the photo-induced union of 3,4-dimethylfuran (19) and / -(benzyloxy)-propanal (18) (see Scheme 5). Irradiation of a solution of these two simple, achiral compounds in benzene with a 450 W Hanovia lamp equipped with a vycor filter results in the exclusive formation of head-to-head, exo photoadduct 17 in 63% yield. As a cw-fused dioxabicyclo[3.2.0]heptene system, intermediate 17 possesses a folded molecular framework to which access is obstructed on the concave face. In the presence of mCPBA, the less hindered convex face of the enol ether double bond is oxidized in a completely diastereoselective fashion, affording intermediate 16 in 80% yield after regioselective opening of... 

They react at different rates with other chiral compounds. These rates may be so close together that the distinction is practically useless, or they may be so far apart that one enantiomer undergoes the reaction at a conveni t rate while the other does not react at all. This is the reason that many compounds are biologically active while their enantiomers are not. Enantiomers react at the same rate with achiral compounds. ... 

It is often possible to convert an achiral compound to a chiral compound by (1) addition of a chiral group (2) running an asymmetric synthesis, and (3) cleavage of the original chiral group. An example is conversion of the achiral 2-pentanone to the chiral 4-methyl-3-heptanone (50). In this case, >99% of the product was the (5) enantiomer. Compound 49 is called a chiral auxiliary because it is used to induce asymmetry and then is removed. 

If the beam of plane-polarized light passes through a solution of an achiral compound ... 

Compound 72 was shown to display enantioselectivity in the extraction of chiral potassium salts from water into the organic phase.105 The supramolec-ular polymer possesses a homochiral helical architecture onto which one of the anionic enantiomers preferentially binds. Intriguingly, for some of the anions the octamer and polymer showed opposite selectivity, illustrating the difference in supramolecular chirality of the two systems. Furthermore, the polymer was capable of inducing a Cotton effect in the achiral compound potassium A-(2,4-dinitrophenyl)glycinate. Since the apolar side chains would... 

Enantiomers have identical chemical and physical properties in the absence of an external chiral influence. This means that 2 and 3 have the same melting point, solubility, chromatographic retention time, infrared spectroscopy (IR), and nuclear magnetic resonance (NMR) spectra. However, there is one property in which chiral compounds differ from achiral compounds and in which enantiomers differ from each other. This property is the direction in which they rotate plane-polarized light, and this is called optical activity or optical rotation. Optical rotation can be interpreted as the outcome of interaction between an enantiomeric compound and polarized light. Thus, enantiomer 3, which rotates plane-polarized light in a clockwise direction, is described as (+)-lactic acid, while enantiomer 2, which has an equal and opposite rotation under the same conditions, is described as (—)-lactic acid. 

An interesting example of the above difference is l-DOPA 4, which is used in the treatment of Parkinson s disease. The active drug is the achiral compound dopamine formed from 4 via in vivo decarboxylation. As dopamine cannot cross the blood-brain barrier to reach the required site of action, the prodrug 4 is administered. Enzyme-catalyzed in vivo decarboxylation releases the drug in its active form (dopamine). The enzyme l-DOPA decarboxylase, however, discriminates the stereoisomers of DOPA specifically and only decarboxylates the L-enantiomer of 4. It is therefore essential to administer DOPA in its pure L-form. Otherwise, the accumulation of d-DOPA, which cannot be metabolized by enzymes in the human body, may be dangerous. Currently l-DOPA is prepared on an industrial scale via asymmetric catalytic hydrogenation. 

Prelog and Helmchen (5) defined pseudoasymmetry as the duality resulting from the two ways with which one can combine two enantiomorphic ligands with two enantiotopic spaces (Fig. 4). This represents an innovation because it limits pseudoasymmetry to achiral compounds (35). This follows from the fact that enantiotopic spaces can exist only if the molecule possesses an element of... 

PLATE I Determination of the enantiomeric purity of active pharmaceutical ingredient (main compound = MC, peak I is the enantiomeric impurity). Conditions lOOmM sodium phosphate buffer pH = 3.0, lOmM trimethyl -cyclodextrin, 60 cm fused silica capillary (effective length 50 cm) X 75 pm I.D., injection 10 s at 35 mbar, 25°C, 20 kV (positive polarity) resulting in a current of approximately lOOpA, detection UV 230 nm. The sample solution is dissolved in a mixture of 55% (v/v) ethanol in water. (A) Typical electropherogram of an API batch spiked with all chiral impurities, (B) overlay electropherograms showing the selectivity of method toward chiral and achiral impurities, a = blank, b = selectivity solution mixture containing all known chiral and achiral compounds, c = API batch, d = racemic mixture of the main compound and the enantiomeric impurity. 

This reaction was first studied in the case of a achiral compound and then applied to the optically active model. ... 

Absolute asymmetric synthesis refers to the situation in which an asymmetric induction occurs in the absence of an externally imposed source of chirality [5]. Such reactions are invariably carried out in the crystalline state, where the asymmetric influence governing the enantioselectivity derives from the spontaneous crystallization of an achiral compound in a chiral space group. This phenomenon, which is analogous to the spontaneous crystallization of racemates as... 

Pharmacokinetics may also form the basis of a decision on the choice of compound from a series for development. It is not uncommon for a company to take three or four compounds of a series as far as the first study in man and to choose for development the compound that is most attractive from the pharmacokinetic point of view. Similarly, the development of achiral compounds rather than racemic mixtures is generally preferred and it may be necessary to establish whether stereoselective metabolism occurs in man and, if so, which enantiomer has the more desirable profile. 

The reaction became particularly interesting for synthetic purposes when enantiose-lective variants were elaborated. Thus, the deprotonation of meio-epoxides like 89 converts an achiral compound into a chiral one, the carbenoid 90. If the lithiation has been carried out with a differentiation of the enantiotopic protons, the subsequent transannular... 

The third approach is the main topic of this volume. According to the definition given above it involves enantiomerically pure starting materials which at some point must be provided by resolution or ex-chiral-pool synthesis. It is more or less equivalent to the term asymmetric synthesis defined by Marckwald in 19047 as follows Asymmetric syntheses are those reactions which produce optically active substances from symmetrically constituted compounds with the intermediate use of optically active materials but with the exclusion of all analytical processes . In today s language, this would mean that asymmetric syntheses are those reactions, or sequences of reactions, which produce chiral nonracemic substances from achiral compounds with the intermediate use of chiral nonracemic materials, but excluding a separation operation. 

The determination of enantiomeric purity (ee) by NMR spectroscopy is usually carried out with the help of a nonracemic chiral auxiliary compound. NMR methods not requiring a chiral auxiliary compound are also known and are based on self-association of the enantiomers or on their reaction with a bifunctional achiral compound (see Section 3.1.4.7.). 

Chemical Transformations Affecting the Chiral Units 4.3.4.2.2.I. Degradation to Achiral Compounds... 

A typical case is summarized below. An intramolecular Diels-Alder reaction of achiral compound 1 yielded a cyclization product with four stereogenic centers. For structural assignment two structures were taken into consideration (i) 2, which would have been formed via an exo-transition slate, and (ii) 3, the en[Pg.486]

TABLE 3. Asymmetric autocatalysis in reaction of 87 initiated by chiral inorganic crystals, inorganic-organic hybrid materials and chiral cocrystals of achiral compounds... 

A unique feature of the transition-metal-catalyzed allylic alkylation is its ability to convert starting materials of various symmetry types, such as racemic, meso- and achiral compounds, into optically pure material, Strategies to effect such transformations derive from recognition of the stereochemical courses in each step of the catalytic cycle and analysis of symmetry elements in the substrate or intermediate. Figure 8E.1 summarizes potential sources of enantio-discrimination in transition-metal-catalyzed allylic alkylation. 

Most of the isomeric guests are achiral compounds, and therefore achiral hosts with variable properties are effective enough to selectively form a molecular complex with one of these hosts. 2,2/-Dihydroxy-l,l/-binaphthyl 17, has been found to... 

An interesting phenomenon whereby achiral compounds occupy chiral cavities has been reported. Steroidal host compounds give rise to the attachment of definite chiral conformations of achiral compounds within cavities, making it possible to observe solid-state circular dichroism spectra. Gdaniec and Polonski reported this type of property for the inclusion compounds of DCA and CA with various aromatic ketones [40a] and benzil [40c], Furthermore, it is possible for the selected conformers to maintain their chiral state temporarily in solution. That is, soon after the inclusion compounds are dissolved, the chirality may be retained for some time. /V-Nitrosopiperidines were found to display this type of dynamic chiral recognition in DCA and CA inclusion compounds [40b], In this case, one can observe the decay of the circular dichroism signal after dissolution of these inclusion compounds in methanol. 

The asymmetric crystallization of achiral compounds is stimulated by autoseeding with the first crystal formed. Although the chiral sense of the spontaneously formed chiral crystals cannot be predicted, seed crystals of the preferred chirality can be added in a more practical procedure to obtain one enantiomorph of a crystal. 

Analytical Properties Resolution of enantiomers such as trans- 1,3-cyclohexene dibenzoate, 3,5-pentylene dibenzoate, 3,5-dichlorobenzoate, triacetylacetonates, and racemic compounds having phosphorus as a chiral center this phase will also resolve achiral compounds Reference 45, 46... 

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