Spiranes, chirality

The property of chirality is determined by overall molecular topology, and there are many molecules that are chiral even though they do not possess an asymmetrically substituted atom. The examples in Scheme 2.2 include allenes (entries 1 and 2) and spiranes (entries 7 and 8). Entries 3 and 4 are examples of separable chiral atropisomers in which the barrier to rotation results from steric restriction of rotation of the bond between the aiyl rings. The chirality of -cyclooctene and Z, -cyclooctadiene is also dependent on restricted rotation. Manipulation of a molecular model will illustrate that each of these molecules can be converted into its enantiomer by a rotational process by which the ring is turned inside-out. ... 

Among other types of compounds that contain the system illustrated in Figure 4.2 and that are similarly chiral if both sides are dissymmetric are spiranes (e.g., 21) and compounds with exocyclic double bonds (e.g., 22). 

A very impressive example of the synthetic utility of this chemistry is the one-pot enantioselective double G-H activation reaction of 86 to generate chiral spiran 87 (Equation (73)).172 In this case, the phthalimide catalyst Rh2(enantiotopically selective aromatic C-H insertions of diazo ketoesters (Equation (74)).216 Moreover, dirhodium(n) tetrakisIA-tetrafluorophthaloyl- )-/ /-leucinate], Rh2(hydrogen atoms of the parent dirhodium(n) complex are substituted by fluorine atoms, dramatically enhances the reactivity and enantioselectivity (up to 97% ee). Catalysis... 

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. 

In addition to this nonequivalence, the imprecise definition of the chirality axis and difficulties in dealing with stereogenic centers in polycyclic structures led to confusion in the case of certain adamantanes, cyclohexanes and spiranes (see Section 1.1.5.3.3.). These problems were solved in the late 1970s and it was recommended1 that the PjM rather than the obsolete aR/aS description be used. This use is recommended as it leads to a considerable simplification of static Stereochemistry. 

Spiranes have caused many problems. The stereomodel 3, of general type 3a, is a good example of where the obvious necessity of specifying stereogenic centers was circumvented by the chirality axis despite too low a symmetry of the skeleton (C2v). 

The chirality observed in this kind of substituted allene is a consequence of dissymmetry resulting from restricted rotation about the double bonds, not because of a tetrahedral atom carrying four different groups. Restricted rotation occurs in many other kinds of compounds and a few examples are shown in Table 13-3, which includes trans-cycloalkenes (Section 12-7), cycloalkyli-denes, spiranes, and ort/zo-substituted biphenyl compounds. To have enantiomers, the structure must not have a plane or center of symmetry (Section 5-5). 

Both the cis- and the trans-disubstituted spiranes resulted, in different ratios, depending on the reaction conditions. Clearly, the trans spiranes are chiral. The first conjugate addition to the Michael acceptors 75a-c is intermolecular in nature and defines the sense of chirality at the first chiral center. Subsequent intramolecular ring closure to the spiranes 76 defines the cis or trans configuration of the product. When cyclohexane-1,3-dione (74a) was reacted with dibenzalacetone (75a) in the presence of ca 5 mol% (—)-quinine (3a, Scheme 4.3), a 2.5 1 trans/cis mixture resulted, with the trans isomer 76 having optical purity of ca 30% (Scheme 4.37) [61] (the absolute configuration of the predominant enantiomer was not assigned). 

Among the several molecular assemblies able to display axial chirality, well known examples include allenes (XXXI), spiranes (XXXII), and biphenyls (XXXIII). 

Molecules that do not possess an asymmetric center may still have nonsuperimposable mirror images and exist as enantiomers. These molecules contain a chiral plane or chiral axis and are dissymmetric with respect to either that plane or axis. The structures of the enantiomers of the sedative-hypnotic methaqualone are presented in Fig. 4. In this molecule there is a chiral axis between the nitrogen atom (N-1) and phenyl ring (C-1). The dissymmetry of the two forms of the molecule is a result of hindered rotation around this axis, which is due to steric interactions between methyl groups (M-1 and M-2). Other axially dissymmetric molecules include allene, biaryls, alkylidenecyclohexanes, and spiranes. Planar dissymmetric molecules are exemplified by molecules such as tra s-cycloalkenes. 

Axial chirality (e.g., spiranes with cyclic skeleton)... 

In this reaction the spirane can be formed but its stereostructure was unknown. The spirane molecule can be chiral only in that case when the two five-membered rings are perpendicular to each other. Optical rotation of the spirane received in this reaction confirmed the structure of the supposed spirane Thus, over Ni-/-quartz catalyst, spirane 3 with assg = -0.066°,... 

Chirality may exist in many molecules that do not possess a chiral center. Such compounds may possess a chiral plane or a chiral axis, and are said to be dissymetric with respect to either that plane or that axis. Certain optically active allenes, biaryls, alkylidenecyclohexanes, and spiranes provide examples of axially dissymmetric molecules (chiral axis), irons-Cycloalkenes exemplify planar dissymmetry in molecules. The configurations of these classes may be specified by the Cahn-Ingold-Prelog convention using the usual R and 5 descriptors. Special subrules, which we will not describe here, are applied to this purpose. The interested reader is referred to references 8 (see p. 43) and 9 for details. Scheme 2.1 presents some molecules that are optically active because of planar or axial dissymmetry, and for which the absolute configurations have been determined. 

Another interesting group of compounds where chirality often occurs is spir-anes (Figure 2.17). It is sufficient to substitute any two hydrogen atoms in both spirane rings with any substituents (they can be identical) to make this molecule optically active. 

Compounds containing nitrogen atom that are capable of forming four bonds and having different substituents may be optically active. In such compounds, there is a certain analogy to a chiral tetrahedral carbon atom. This type of compounds includes ammonium salts, amine oxides, and spiranes where nitrogen atom is a central one (Figure 2.26). 

Axial chirality the atoms are placed in two perpendicular planes that are nonsymmetrical and cannot rotate freely (allenes, cumulenes, spiranes, and substituted ortho-biphenyls). 

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