Chiral introduction

The enantioselective introduction of chiral centres into an achiral molecule can nowadays be achieved most easily using chiral reductants or oxidants. 

A similar effect occurs in highly chiral nematic Hquid crystals. In a narrow temperature range (seldom wider than 1°C) between the chiral nematic phase and the isotropic Hquid phase, up to three phases are stable in which a cubic lattice of defects (where the director is not defined) exist in a compHcated, orientationaHy ordered twisted stmcture (11). Again, the introduction of these defects allows the bulk of the Hquid crystal to adopt a chiral stmcture which is energetically more favorable than both the chiral nematic and isotropic phases. The distance between defects is hundreds of nanometers, so these phases reflect light just as crystals reflect x-rays. They are called the blue phases because the first phases of this type observed reflected light in the blue part of the spectmm. The arrangement of defects possesses body-centered cubic symmetry for one blue phase, simple cubic symmetry for another blue phase, and seems to be amorphous for a third blue phase. 

One often encountered but usually undesirable consequence of backbone modification is the introduction of a chiral center at the phosphoms. Although chiral syntheses are being explored, all commonly used synthetic methods yield a mixture of diastereomers having either R or configuration. 

In common with the naturally occurring carbapenem thienamycin (2), the introduction of the /n j -6-[l-(R)-hydroxyethyi] group had a profound effect on the biological properties of the penems. This, together with an indication from an early study (93) that, as with other P-lactams, the 5(R)-enantiomer was solely responsible for antibacterial activity, provided impetus for the development of methods for the synthesis of chiral penems. 

Aziridines have been prepared stereospecifically by the nucleophilic addition of the nitrogen residue to alkenes <80T73). Introduction of the nitrene is accomplished readily via a Michael-type addition with free diphenylsulfilimine (Scheme 12), and where a chiral sulfilimine is used the chirality is transferred to the aziridine with optical yields in excess of 25%. 

The introduction of a THP ether onto a chiral molecule results in the formation of diastereomers because of the additional stereogenic center present in the tetrahy-dropyran ring (which can make the interpretation of NMR spectra somewhat troublesome at times). Even so, this is one of the most widely used protective groups employed in chemical synthesis because of its low cost, the ease of its installation, its general stability to most nonacidic reagents, and the ease with which it can be removed. 

Asymmetric Diels-Alder reactions using a dienophile containing a chiral auxiliary were developed more than 20 years ago. Although the auxiliary-based Diels-Alder reaction is still important, it has two drawbacks - additional steps are necessary, first to introduce the chiral auxiliary into the starting material, and then to remove it after the reaction. At least an equimolar amount of the chiral auxiliary is, moreover, necessary. After the discovery that Lewis acids catalyze the Diels-Alder reaction, the introduction of chirality into such catalysts has been investigated. The Diels-Alder reaction utilizing a chiral Lewis acid is truly a practical synthetic transformation, not only because the products obtained are synthetically useful, but also because a catalytic amount of the chiral component can, in theory, produce a huge amount of the chiral product. 

A mechanism for this reaction has been proposed [75], The first key intermediate in the reaction is the copper(I) acetylide 42. The additional ligand may be solvent or H2O. The acetylene moiety in 42 is activated for a 1,3-dipolar cycloaddition with the nitrone to give intermediate 43, with introduction of chirality in the product. A possible route to ris/traws-41 might be via intermediate 44. Finally, the cis isomer is isomerized into the thermally more stable trans-41. It should be mentioned that the mechanism outlined in Scheme 6.32 was originally proposed for a racemic version of the reaction to which water was added. 

The introduction of synthetic materials into natural products, often described as adulteration , is a common occurrence in food processing. The types of compounds introduced, however, are often chiral in nature, e.g. the addition of terpenes into fruit juices. The degree to which a synthetic terpene has been added to a natural product may be subsequently determined if chiral quantitation of the target species is enabled, since synthetic terpenes are manufactured as racemates. Two-dimensional GC has a long history as the methodology of choice for this particular aspect of organic analysis (38). 

Chiral additives have been shown to be very effective for chiral separations by capillary electrophoresis (CE) [4, 5]. Indeed, it may be argued that there has been considerably more research activity in chiral separations by CE than by EC methods since the introduction of the former technique. Chiral additives in CE have several advantages, some of which are highlighted in Table 11-2. 

With chiral auxiliaries1,41 a remote chiral moiety is temporarily introduced into the substrate in order to direct the nucleophilic addition diastereoselectively. The chiral auxiliary can be removed from the initial addition product with complete conservation of the chirality of the desired product and also of the chiral auxiliary. The recovered chiral auxiliary can then be reused in further reactions. Therefore, chiral auxiliaries are used to chiralize an a priori achiral carbonyl substrate by the introduction of a covalently bound, but nevertheless easily removable, chiral source. 

In the more successful reagents, the ligands have been selected in such a way that the metal center remains nonstereogenic, this has been achieved mainly by application of chiral diols with C2 symmetry or by introduction of two of the same alkoxy residues. 

Introduction of substituents to the cyclopentadienyl ring of 7, or the use of complexes derived from other monodentate chiral alcohols, cause decreased enantioselectivity11,1 la,35a 36. 

In addition to ketone enolates, azaenolatcs with chiral auxiliary groups attached to the nitrogen atom are suitable for the introduction of an a-unsubstituted enolate of the keto-type into an aldehyde in a stereoselective manner (see Section D.1.3.5.). 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

The second option involves the incorporation of either chiral amines or chiral alcohols into the heteroatom-carbene side chain (R ), which represents the most versatile approach to diastereoselective benzannulation. The optically pure (2R,3R)-butane-2,3-diol was used to tether the biscarbene complex 37. The double intramolecular benzannulation reaction with diphenylbutadiyne allowed introduction of an additional stereogenic element in terms of an axis... 

From this discussion it is clear, that, independently of their redox properties, suitably modified electrodes offer themselves for the introduction of diastereo- or enantioselectivity into electrochemistry. Early reports of chiral inductions at modified electrodes include reactions at graphite and SnO surfaces derivatized with monolayers of (S)-(—)-phenylalanine. Asymmetric inductions at the chiral graphite electrode could, however, not be verified in other laboratories even after great efforts... 

Enzyme-mediated oxidation reactions offer highly diverse options for the modification of existing functional groups as well as for the introduction of novel function in chiral catalysis. Biooxidations often enable us to obtain complementary solutions to metal-assisted transformations and organocatalysis and are considered one of the important strategies of green chemistry . 

One 7i-bond of an aromatic ring can be converted to a cyclohexadiene 1,2-diol by reaction with enzymes associated with P. putida A variety of substituted aromatic compounds can be oxidized, including bromobenzene, chlorobenzene, " and toluene. In these latter cases, introduction of the hydroxyl groups generates a chiral molecule that can be used as a template for asymmetric syntheses. " ... 

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