Axially-chiral biphenyls

Interestingly, the hydroformylation results obtained with ligands 2b and 2d, which have conformationally flexible axially chiral biphenyl moieties, are similar to those obtained with ligand 2m, which have conformationally rigid binaphthyl moieties. This indicates that diphosphite ligands that contain the conformationally flexible axially chiral biphenyl moieties predominantly exist as single atropoisomer in the [RhH(CO)2 (diphosphite)] complexes... 

Welseloh, G. Wolf, C. Konig, W.A. New technique for the determination of interconversion processes based on capillary zone electrophoresis Studies with axially chiral biphenyls. Chirality 1996, 8, 441-445. 

Atropisomerism is significant because it introduces an element of chirality in the absence of stereogenic atoms. Axial chirality is observed with stereoisomers (or atropisomers) that result from hindered rotation about a single C—C or C—N bond. The barrier of rotation between atropisomers must be high enough to allow for their isolation. A minimum of three or/ho-substituents are generally required for an axially chiral biphenyl to have substantial stability toward racemization at room temperature. For general definitions and descriptions, see references [3-5]. 

Morimoto T, Yoshikawa K, Murata M, Yamamoto N, Achiwa K. Preparation of axially chiral biphenyl diphos-phine ligands and their application in asymmetric hydrogenation. Chem. Pharm. Bull. 2004 52(12) 1445-1450. 

Oxidation of aknadinine with silver nitrate gave a pair of dimeric compounds, one of which was identical to the naturally occurring bisaknadinine (8) and the other assumed to be a stereoisomer arising from an axial chirality concerning the mode of biphenyl linkage (21,22). It was impossible, however, to determine from ORD and CD measurements whether the isomer is of natural bisaknadinine (8). Therefore, unambiguous proof of the stereochemistry was achieved, using the X-ray diffraction method, and the... 

As shown in Scheme 8-11, nucleophilic entry from the a-face (24a) may be hindered by the sterically bulky substituent R2 on the oxazoline moiety therefore entry from the / -face 24/ predominates. Free rotation of the magnesium methoxy bromide may be responsible for the sense of the axial chirality formed in the biaryl product. If the azaenolate intermediate 25 is re-aromatized with a 2 -methoxy substituent complexed to Mg, (iS )-biphenyl product is obtained. Upon re-aromatization of azaenolate 25B, (R)-product is obtained. 

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... 

The absolute configuration of axially chiral (phenylmethylene)cyclobutane derivative 6 is similarly determined from the exciton Cotton effect due to the coupling of the styrene and l,f-biphenyl chromophore transition dipoles144. 

Besides BINAP or p-TolBINAP, optically active peraryldiphosphines with axial chirality based on the biphenyl groups (6,6 -dimethylbiphenyl-2,2 -diyl)bis(diphenylphosphine) and its analog are also effective ligands for the asymmetric isomerization as expected [21],... 

Research utilizing the thiepine skeleton in material science has been reported. For example, liquid crystals with chiral dihydrodibenzo[c,i ]thiepines were studied. The enantiomerically pure (-)-(i )-3,9-bis[4-(dodecyloxy)benzoyl-oxy]-5,7-dihydro-l,l l-dimethyldibenzoR,f]thiepine 80 and (—)-(R)-3,9-bis[4-(dodecyloxy)benzoyloxy]-5,7-dihydro-1,1 l-dimethyldibenzoR,f]thiepine dioxide 82 display smectic C mesophases by a rigid twisted biphenyl core and axial chirality <1998JOC3895>. 

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

Optical activity can also be induced on achiral azobenzene units when they are incorporated into the polymer main chains through covalent bonding to chiral subunits (34-37 in Fig. 14) [88-92]. Axially chiral amino- or carboxy-substituted biphenyl and binaphthyl and tartaric acid derivatives were used as the optically... 

The heterocyclic hemi-aminal 44 was formed as a model for the synthesis of the marine alkaloids zoanthamine and zoanthenol and is derived from the cyclic imine formed by the reduction of an appropriated substituted azide <07H(72)213>. A pyrrolidine-fused azepine has been isolated from the venom of the ant Myrmicaria melanogaster and assigned as 45 based upon GC and FT-IR comparison with synthetic material <07JNP160>. The axially chiral doubly bridged biphenyl azepine 46 has been synthesised and used with oxone as an epoxidation catalyst in a biphasic system <070BC501>. 

Berger, U. Vetter, W. Gotsch, A. Kallenbom, R., Chromatographic enrichment and enantiomer separation of axially chiral polybrominated biphenyls in a technical mixture J. Chromatogr. A 2002, 973, 123-133. 

It is not strictly necessary to introduce the 1,1 -binaphthyl backbone. For axial chirality, the biphenyl scaffold is sufficient, provided that rotation around the phenyl-phenyl axis is sufficiently hindered. Hoveyda combined this reduced axial chiral motif with additional central chirality in the imidazole backbone (O and C ) [6,7], Synthetically, the task is accomplished by Buchwald-Hartwig amination of enantiomerically pure (H ,21 )-diphenylethylenediamine with 1-methoxy-I -iodo-biphenyl and subsequent reaction with mesityl bromide to introduce the bulky wingtip group on the second amino group of the chiral starting material. Ring closure reaction with triethyl orthoformate and hydrolysis of... 

Figure 5.21 Synthesis of a chiral hydroxy functionalised imidazolium salt on an axially chiral i, 1 -biphenyl scaffold.

The other primary application of asymmetric Grignard coupling reactions has been in the synthesis of axially chiral binaphthyl and biphenyl derivatives. Hayashi performed a binaphthyl synthesis (equation 6) in 95% ee using a nickel catalyst and ligand (7), a P-O chelating analog to (3). For a similar synthesis of chiral biaryls (equation 7) ligand, (8) was found to yield the most successful results (93% ee). ... 

Ring closing methodology was also used to access the axially chiral dibenz-fused lactams 39 and 40 from the unsymmetrically substituted biphenyls 38 and (7f)-phenylglycinol high yields and diastereselectivities were obtained. The relative stereochemistry of the minor diastereomer 40 was established via a NOES Y experiment <03 JOC9517>. 

Tetrasubstituted biphenyls (46) exhibit axial chirality because of geometric constraints needed to reduce steric hindrance of the substituent groups. Addition of Eu(tfc)3, Pr(tfc)3 and Pr(hfc)3 to derivatives of 46 with suitable donor groups caused enantiomeric discrimination in the H NMR spectra. The ( l-isomer typically exhibited larger shifts in the spectrum . 

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