Chiral biaryls examples

Van Leeuwen s studies using diphosphite ligands 2 and 18 indicated that the stability and catalytic performance of the [RhH(CO)2(diphosphite)] species depends strongly on the configuration of the 2,4-pentanediol ligand backbone and the chiral biaryl phosphite moieties. Thus, for example, ligands 2b, 2d and 2m, which form well defined stable bis-equatorial (ee)... 

However, a more exciting application of this reaction is the oxazoline-directed synthesis of axially chiral biaryls. The oxazoline system not only activates the ortho-methoxy group for nucleophilic displacement but also determines the stereochemical outcome of the reaction. This provides a convenient method for the introduction of axial-chirality. Meyers group continues their earlier lead on this subject with reports of the stereoselective synthesis of tetrasubstituted biphenyls 391,392 examples are shown in Table 8.29 (Scheme 8.154). The best... 

Three types of reaction systems have been designed and applied for the enantioposition-selective asymmetric cross-coupling reactions so far. First example is asymmetric induction of planar chirality on chromium-arene complexes [7,8]. T vo chloro-suhstituents in a tricarhonyl("n6-o-dichlorobenzene)chromium are prochiral with respect to the planar chirality of the 7t-arene-metal moiety, thus an enantioposition-selective substitution at one of the two chloro substituents takes place to give a planar chiral monosubstitution product with a minor amount of the disubstitution product. A similar methodology of monosuhstitution can be applicable to the synthesis of axially chiral biaryl molecules from an achiral ditriflate in which the two tri-fluoromethanesulfonyloxy groups are enantiotopic [9-11]. The last example is intramolecular alkylation of alkenyl triflate with one of the enantiotopic alkylboranes, which leads to a chiral cyclic system [12], The structures of the three representative substrates are illustrated in Figure 8F.1. 

The enantioselective complexation technique can also be applied as one step in the reaction sequence, providing chiral substrates for the next step. We will now discuss the example of Gabriel synthesis between potassium phthalimide 41 and alkyl bromide 42, which leads to optically active amines (Scheme 1) [51], Instead of the complicated preparation of chiral alkyl bromides (halides), imides (43), which are reaction intermediates, have been resolved. Upon treatment with hydrazine and KOH, these gave optically active amines. The chiral host (S,S)-(-)-6 or the chiral biaryl host (,S>(-j-40 was used for the effective resolution of the intermediates 43. Racemic mixtures 43a-d were resolved by complex formation with the host (S,S)-(-)-6 in a mixture of diethyl ether and light petroleum. 

None of these derivatives has been shown to provide higher levels of selectivity for the KR of aryl alkyl sec-alcohols than Fu s catalyst 4b, although several are more readily prepared. For example, the axially chiral biaryl DMAP 12a developed by Spivey [81-90] is relatively readily prepared but provides only modest levels of selectivity for the KR of aryl alkyl sec-alcohols s < 30 at —78 °C over 8-12 h or s < 15 at rt in 20 min (Table 8.3) [91]. 

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. ... 

In a study of catalytic asymmetric cross-cyclotrimerization leading to axially chiral biaryls, one example was reported for 3-(l-naphthyl)pyri-dine derivative 269, without mentioning the chirality of the obtained compound (07CEJ1117). 

A review by Bringmann, Breuning et al. (05AG(1E)5384) entitled Atroposelective synthesis of axially chiral biaryl compounds contains a few examples of heteroaromatic compounds but methodologically it is of... 

Chiral allenes are another example of molecules that are chiral, but that do not contain a chirality center. Like the chiral biaryl derivatives that were described in Section 7.9, chiral allenes contain an axis of chirality. The axis of chirality in 2,3-pentadiene is a line passing through the three carbons of the allene unit (carbons 2, 3, and 4). 

The efficacy and the chiral leaving group-induced enantioselectivity in the Meyers synthesis of axially chiral biaryls of some selected examples are given in the Table 1. 

Biaryls with axial chirality are potentially important as chiral ligands for asymmetrical reactions and also as intermediates for synthesizing biologically active natural biaryl compounds, for example, michellamine in Eq. 66. (ii -Disubstituted arene)chromium tricarbonyl complexes exist in two enantiomeric forms based on planar chirality. Biaryl coupling provides a new approach to synthesizing both optically pure atropisom-ers starting from a single chiral arene chromium complex (Eq. 75). ... 

The transition metal-catalyzed [2+2+2] cycloaddition has been applied to the atroposelective biaryl synthesis. The first example is the chiral cobalt(I) complex-catalyzed [2+2+2] cycloaddition of aryl-diynes with nitriles to produce axially chiral arylpyridines [19a]. Subsequently, the enantioselective synthesis of axially chiral biaryl phosphine oxides has also been achieved (Scheme 21.16) [19b]. 

Bringmann and co-workers have reported highly efficient atropo-enantioselective reduction using OABs as chiral inducers to give one atropisomer with high enantiose-lectivities [76]. For example, the reduction of biaryl lactones 51 with BH3 THF (4 equiv.) in the presence of 2b (3 equiv.) in THF at 30 °C provided chiral biaryl alcohol 52 with up to 97% ee (Scheme 11.15). 

Synthetic highlights The Cu-promoted catalytic decarboxylative, biaryl synthesis of valsartan is an example of biomimetic, aerobic decarboxylation and enables C-C bond formation in aqueous solution. The chiral variant of biaryl synthesis is exemplified by the stereoselective approach to the axially chiral biaryl system present in vancomycin. 

The enantioselective completely intramolecular [2 + 2 + 2] cycloaddition also furnishes Cz-symmetric axially chiral biaryls. Shibata et al. reported the cationic rhodium(I)/tol-BINAP complex-catalyzed enantioselective [2 + 2 + 2] cycloaddition of symmetric hexaynes 58 to give Cz-symmetric axially chiral biaryls 59 with good yields and ee values (Scheme 9.21) [21]. This is the first example of an axially chiral bis(biphenylene) skeleton. 

Selected examples of naturally occurring axially chiral biaryl-compounds, which as a result of restricted rotation about the C—C-bond exist as two atropisomers, are illustrated in Figure 1.25. Among them, vancomycin (a glycopeptide antibiotic used in prophylaxis and in the treatment of... 

FIGURE 1.25. Selected examples of naturally occurring axially chiral biaryl compounds. 

Chiral bisphosphine ligands have found extensive applications in asymmetric catalysis, which is an important reaction in the synthesis of natural products. In 2003, Fujihara reported the first example of bisphosphine-stabihzed Pd nanoparticles [50], 2,2 -Bis(diphenylphosphino)-l,T-binaphthyl (BINAP), a chiral biaryl... 

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