Axial chiral compounds

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. 

Recently, two new axially chiral compounds 44 and 45 have been prepared [44, A-acryl-A-allyl-o-t-butylanilide 45, A-(o-t-butylphenyl)-2-methyl-maleimide]. This represents the first instance of using nonbiaryl axially chiral ligands in asymmetric Dield-Alder reactions. In the presence of iodine, high endo-facial and diastereofacial selectivities have been obtained in 44/45-medi-ated reactions.10... 

This survey deals with organic structures possessing a plane of chirality (see 1.2.) and reviews the more recent results covering approximately the last ten years. Whereas obviously it would be an impossible task to deal with centro or even axial chiral compounds in one review, the field of planar chiral structures can still be surveyed, especially as there is some excellent background material covering several aspects10 18) (but to date no comprehensive survey has been published). These reviews will serve as the basis for some discussions presented in this article. 

Introduction of the allene structure into cycloalkanes such as in 1,2-cyclononadiene (727) provides another approach to chiral cycloalkenes of sufficient enantiomeric stability. Although 127 has to be classified as an axial chiral compound like other C2-allenes it is included in this survey because of its obvious relation to ( )-cyclooctene as also can be seen from chemical correlations vide infra). Racemic 127 was resolved either through diastereomeric platinum complexes 143) or by ring enlargement via the dibromocarbene adduct 128 of optically active (J3)-cyclooctene (see 4.2) with methyllithium 143) — a method already used for the preparation of racemic 127. The first method afforded a product of 44 % enantiomeric purity whereas 127 obtained from ( )-cyclooctene had a rotation [a]D of 170-175°. The chirality of 127 was established by correlation with (+)(S)-( )-cyclooctene which in a stereoselective reaction with dibromocarbene afforded (—)-dibromo-trans-bicyclo[6.1 0]nonane 128) 144). Its absolute stereochemistry was determined by the Thyvoet-method as (1R, 87 ) and served as a key intermediate for the correlation with 727 ring expansion induced... 

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. 

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). 

Scheme 5.22 Pd-catalyzed C—H bond iodination to synthesize axially chiral compounds reported hy Gu and You.

Certain heterocycles, e.g. pyridines or quinolines, bearing of an electron-withdrawing group such as oxazoline, undergo the Michael-type nucleophilic 1,4-addition accompanied with loss of aromaticity to give the new C-C bond. Thus formed dihydropyridine or benzodihydropyridine can be oxidatively aromatized with conservation of chirality, primary induced by an influence of chiral oxazoline moiety. In this manner, Meyers and coworkers [27] described the Michael-type addition of 1-naphthyllithium (609) to the oxazoline 610 at low temperature to form 611 in 90% yield. The latter was oxidatively aromatized to the naphthylquinoline 612 in 87% yield with 88 12 ratio of two diastereomers. Diastereoselectivity in this reaction remained on the same level as obtained by the nucleophilic addition of 609 to 610 indicating the virtually complete conservation of chirahty, from sp -type in the compound 611 to the axially chiral compound 612, Scheme 11. 

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

The absolute configuration of axially chiral compounds can alternatively be specified by M and P which also apply to planar chiral compounds see reference [1],... 

Many axially chiral compounds are Privileged Chiral Ligands . It means that it is highly probable that their application will lead to high enantioselectivity and/or activity of the resulting chiral catalysts. It is no wonder that many efforts have been made in order to attach axially chiral substiments, for example easily available... 

Scheme 7.22. Kinetic resoiution of racemic aidehydes to give axially chiral compounds.

The synthesis of axially chiral compounds via the transition-metal-catalyzed enan-tioselective [2 - - 2 - - 2] cycloaddition is described in this chapter. Cobalt-, iridium-, and rhodium-based catalysts are currently available for this purpose. The characteristic of these three catalysts may be summarized as follows. 

The author is well aware of the fact that many chemists still advocate use of the traditional RIS symbols also for at least some, if not all, compound types with helical stereogenic units, even if these are not in concordance with the proper helicity descriptors as in the case of axially chiral compounds where A M and A P. For the sake of consistency,... 

Finally, a conceptually new approach is the application of cycloisomerization processes to the enantioselective synthesis of axially chiral compounds. The method has been introduced by Tanaka [25]. It involves 1,5-enynes with an... 

Fig. 10.13 Enantioselective construction of axially chiral compounds by enyne cycloisomerization [25]...

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