Chiral compounds biaryls

Axial Chirality. For a system with four groups arranged out of the plane in pairs about an axis, the system is asymmetric when the groups on each side of the axis are different. Such a system is referred to as an axial chiral system. This structure can be considered a variant of central chirality. Some axial chiral molecules are allenes, alkylidene cyclohexanes, spiranes, and biaryls (along with their respective isomorphs). For example, compound 7a (binaphthol), which belongs to the class of biaryl-type axial chiral compounds, is extensively used in asymmetric synthesis. Examples of axial chiral compounds are given in Figure 1-5. 

The hindered biaryls are examples of a different type of chiral compound due to their rotational restriction around a C C single bond. As long as the ortho-substituents in a compound such as 23 are bulky enough, the compound can exist in two forms, 23 and its enantiomer 23, which are not interconvertible. 

Reactions like these, in which stereoselectivity is the consequence of steric hindrance to bond rotation, are most well known among the biaryls, and derivatives of binaphthyl have provided chemists with a valuable range of chiral ligands [4-6]. But the biaryls are only a small subset of axially chiral compounds containing two trigonal centres linked by a rotationally restricted single bond. Many others are known, some with much greater barriers to rotation than Fuji s enol ether [7]. Yet until quite recently there were no reports of reactions in which nonbiaryl atropisomers were the source, conveyor, or product of asymmetric induction. 

Other Compounds. In theory, any chiral compound with a reactive functional group can be derivatized with (5)- or (R)-MTPA in order to assess its enantiomeric purity. An example is the derivatization of cyclic carbamates, followed by H NMR analysis (eq 1). Similarly, axially chiral biaryls bearing amine or alcohol substituents, e.g. (16) and (17), have been analyzed via the corresponding MPTA derivatives. ... 

The alkaloids have also been used for the resolution of various phosphoric and carboxylic adds 4—10, including axially chiral compounds, such as biaryl derivatives 4, 5 and 7 [13], allenic acids 9, and planar chiral naphthalenophane carboxylic acids 10 (Figure 13.5). 

Chiral ligand 651 is obtained from the appropriate natural amino-acid phenylalanine, whereas the corresponding derivatives of valine or leucine proved to be slightly less effective [46], Axially prochiral, enantiotopic, biaryl-2,6-diols have been converted to the respective chiral compounds via enzymatic desymmetrization. Thus Pseudomonas cepacia lipase (PCL) catalysed the atropisomerically-selective hydrolysis of diacetate 654 to give monoacetate 655 in 67% yield and 96% e. e. [47], Scheme 24. 

The two most important classes of axially chiral compounds which will be considered here are the allenes and hindered biaryls. 

Axes of chirality compounds showing atropisomerism Biaryls X5-X7... 

The [2 -I- 2 -I- 2] cycloaddition reaction can give rise to chiral compounds, especially biaryls [3q]. Control of the enantioselectivity in such transformations is of prime importance, notably because biaryls can be used as ligands in asymmetric catalysis. This topic is covered in detail in Chapter 9. Nowadays, cobalt still looks like a poor relation in this field, which is largely dominated by rhodium. Nevertheless, a report from Heller et al. shows for the first time that phosphorus-bearing axially chiral biaryls 9 can be formed by enantioselective benzene formation using the neomenthyl-indenyl cobalt complex II as a catalyst (Scheme 1.3) [7]. Good yields... 

Axes of Chirality compounds showing atropisomerism Biaryls X4 ... 

The nomenclature for biaryl, allene, or cyclohexane-type compounds follows a similar rule. Viewed along the axis, the nearer pair of ligands receives the first two positions in the order of preference, and the farther ligands take the third and fourth position. The nomination follows a set of rules similar to those applied in the central chiral system. In this nomination, the end from which the molecule is viewed makes no difference. From whichever end it is viewed, the positions remain the same. Thus, compound 7a has an ( -configuration irrespective of which end it is viewed from. 

Preparation of the chiral biphenyls and binaphthyls with high enantiose-lectivity can be achieved via substitution of an aromatic methoxyl group with an aryl Grignard reagent using oxazoline as the chiral auxiliary.38 Schemes 8-10 and 8 11 outline the asymmetric synthesis of such chiral biaryl compounds. 

The use of diazodicarboxylates has been recently explored in Cinchona alkaloid catalyzed asymmetric reactions. Jprgensen [50] reported the synthesis of non-biaryl atropisomers via dihydroquinine (DHQ) catalyzed asymmetric Friedel-Crafts ami-nation. Atropisomers are compounds where the chirality is attributed to restricted rotation along a chiral axis rather than stereogenic centers. They are useful key moieties in chiral ligands but syntheses of these substrates are tedious. 

In a tour de force in 1956, Cahn, Ingold and Prelog introduced the terms chirality axis (descriptors aR/aS) and chirality plane (descriptors pRjpS) in order to deal with compounds such as allenes, biaryls and cyclophanes. Rules for assigning the chirality sense were devised ad hoc. In 1966 the helieity concept was introduced and it was recognized that its use allows the corresponding models to be treated in an alternative way. The specific proposals, as illustrated in Table 1, however, were only published in 19821. 

Substituted dibenzothiophenes 156 react with Grignard reagents to give products of the thiophene ring cleavage. With a chiral Ni catalyst, axially chiral biaryl compounds 157 can be obtained in high enantioselectivities (equation 93) . ... 

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