Chirality in the backbone

Unfortunately, no transition metal complex was synthesised, although the combination of a pendant OH functionality and chirality in the backbone of the imidazolidin ring holds great promise for asymmetric homogenous catalysis. 

When coordinated to the metal, the chiral ligand plays an important role in the control of enantioselectivity during the course of the catalysis reaction. These ligands can contain chirality in the backbone (e.g.. CHIRAPHOS, 1), at the phosphorus atom (e.g., DIP AMP, 2), or atropisomerically from C2 symmetric axial configurations (e.g., BINAP, 3). Typically, most chiral ligands possess di-phenylphosphine moieties (Figure 1). 

Helical columns of bifunctional ureidotriazines have also been created in water.40 In this solvent the aromatic cores of compound 39 stack and create a hydrophobic environment that favors the formation of intermolecular hydrogen bonds. The chiral side chains can express their chirality within the columnar polymer because of the helicity generated by the backbone. In contrast, for monofunctional 68 water interferes with the hydrogen bonding and 68 does not stack to form a column. As a consequence the chiral side chain does not express its chirality in the aromatic system. For 39, the bifunctional nature allows for a high local concentration of stacking units. A comparison might be made here to the individual DNA bases that also do not dimerize and stack in water, unless they are connected to a polymer backbone. 

In chiral ligand 24, the two cyclopentane rings restrict the conformational flexibility of the nine-membered ring, and the four stereogenic centers in the backbone dictate the orientation of the four R-phenyl groups. Scheme 6 15 shows the application of Rh-24 in the asymmetric hydrogenation of dehy-droacylamino acids. 

The reaction is quite sensitive to the chiral ligand used. Diphosphines with an axially disymmetric biaryl moiety in the backbone give the best results. The effectiveness of p-Tol-BINAP as ligand, for example, is similar to that of BINAP. The related atropisomeric ligand BIPHEMP can also be used [9]. Among chiral aliphatic diphosphines tested, CyDIOP, which only differs from DIOP in the type of P-substituents, also gives satisfactory results. 

A related group was developed by Gravel et al., for the protection ofketones. Thus, a diol derivative was used to form a ketal (under the usual acidic conditions), which was quite stable under acidic conditions (Scheme 13.6) [28, 29] but was, unfortunately, degraded under basic conditions. The introduction of a second aromatic group in the backbone, and provision of a single enantiomer of the diol (thus allowing the protection of chiral ketones without making pairs of diastereoisomers) partially solved the base-stability problem [30]. 

In conclusion, while the first chiral imidazolinylidenes tested in asymmetric catalysis only gave a moderate chiral induction, more recent results have clearly indicated that the encoding of chiral information in the backbone of the heterocycle may give rise to highly efficient stereodirecting ligands. The potential versatility of this approach is apparent in a recent contribution... 

In most of these ligands the chiral center is far removed from the site where the prochiral substrate coordinates to the transition metal, so that little diastereo-differentiation might be expected. However, the chirality of the backbone controls the conformation of the bulky diarylphosphine groups and hence generates a chiral pocket around the metal, with aryl groups in axial and equatorial positions. This imposes C2 symmetry on the complex, as shown in (22-X). Viewed from the side, such a complex can schematically be divided into sterically hindered and open quadrants (22-XI). A prochiral substrate will then naturally bind with the jr-face that leads to the product with the least steric repulsion. 

As we have seen in Chapter 1, it is very difficult to introduce chirality in the inamedi-ate vicinity of the carbene centre [23,24,46], An elegant way to circumnavigate this is to introduce a functional group on the carbene that can act as the carrier of chirality in the metal complex (see Figure 2.6). Excellent examples are a Cp scaffold for planar chiraUty [47 9] or the binaphthyl group for axial chirahty [50-52], The tether itself can be used as the chiral backbone as is the case in functionalised carbenes derived from 1,2-diamino cyclohexane [53,54],... 

A more conventional approach towards a sulphur functionalised NHC ligand is presented by Seo et al. [273] and follows the traditional phosphane route. Indeed, the thioether functionality takes the place of the phosphino group (see Figure 4.90). The final sulfur functionalised NHC ligand has already two chiral elements, an asymmetric carbon centre in the backbone and planar chirality associated with the Fc group. In addition, the thioether functionality is prochiral and becomes asymmetric upon coordination to a transition metal. 

Advantage Sterically more demanding wingtip groups than mesityl can be introduced into the carbene alongside chiral centres in the backbone (O and O). 

So far, we have considered protocols that result in chiral centres in the C and position (actnally always with the same substiment). Let us now turn to satnrated carbenes that have only one chiral centre in the backbone. Figure 5.15 shows a procedure that utilises a chiral diamine derived from proline, a naturally occurring a-amino acid. Reaction with aniline to the corresponding amide and reduction with LiAlH yields the diamine used [60]. The actual synthesis of the chiral carbene then calls for reaction of the proUne derived diamine with thiophosgene and subsequent S/Cl exchange with oxalyl chloride [50]. The... 

Another interesting and more general methodology to a carbene with only one chiral carbon atom in the backbone was introduced by Hahn et al. [61] (see Figure 5.16). Here, an arylamine is treated with n-BuLi and carbon disulfide to the corresponding thiocarbonic acid amide. Second deprotonation with 5ec-BuLi and subsequent reaction with an asymmetrically substituted Schiff base affords the imidazolidinone that can be reduced with Na/K alloy to the respective carbene. Chirality is introduced via the prochiral N=C bond of the Schiff base and the prodnct is usually a racemate since no chiral discriminator is present in the formative step. 

Figure 5.16 Synthesis of a chiral carbene with only one asymmetric centre in the backbone.

---