Unsymmetrical chiral biaryls

The cross coupling reactions of aryl halides or aryl triflates with arylmetals catalysed by palladium(O) has found extensive use in the synthesis of unsymmetrical biaryls (ref. 27). A recent application of this coupling approach in the presence of chiral planar chromium complexes (ref. 25) has proved fruitful in the synthesis of chiral biaryls. Furthermore, Cr(CO)3-complexed biaryls can be isomerised under thermodynamic control, providing access to both atropisomers. Heating a solution of the complexed biaryl 37 in xylene under reflux resulted in a 1 99 ratio favouring the isomerised biaryl chromium complex 38 (ref. 28)... 

Recently, the use of a chiral catalysts in the asymmetric biaryl synthesis has received some attention. Unsymmetrical chiral binaphthyls can be obtained in high enantiomeric excess by SnAt reactions of naphthylimines such as 39 with lithium bromide free 1-naphthyllithium catalysed by a chiral ether ligand 40 (ref. 29). Another example is the Ni(0) catalysed cross coupling of naphthyl Grignard reagents and naphthyl bromides in the presence of a chiral ferrocene ligand (ref. 30). 

Using other chiral 1,2-diols such as 1,2-diphenyl-1,2-ethanediol or 2,3-butanediol, the Lipshutz approach allows to rich very high diastereoselectivity [19]. Among reactions that have been used in the diastereoselective synthesis of unsymmetrical axially chiral biaryls, beside Ullmann and Lipshutz reactions, are the Suzuki-Miyaura and Meyers synthesis of biaryls. 

Nishii et al. reported metal-mediated benzannulation reaction of diaryl(gm-dichlorocyclopropyl)methanols to synthesize unsymmetrically substituted a-arylnaphthalenes [61]. In particular. The reaction of optically active alcohol 145 in the presence of 1 equiv of HCU at —78 °C afforded chiral biaryl 146 with an excellent level of stereo induction (Scheme 27.48) [62]. It should be noted that chi-raUty exchange from sp central chiraUty to axial chirality takes place in this process. This methodology has been employed successfully for total synthesis of natural lignin lactones, justicidin B, and dehydrodesoxypodophyllotoxin (Scheme 27.49) [63]. 

Carbanion-induced ring transformations of pyran-2-ones include their conversion into unsymmetrical biaryls <07TL7283>, axially chiral quateraryls <07JOC7765>, 2-amino-isophthalonitriles <07T10971>, arylated indans <07T10300> and pyrano[3,4-c]pyran-l,8-diones <07TL8998>. 

An unsymmetrical salen ligand bearing a Lewis base catalyses Ti(OPr-i)4-promoted addition of TMSCN to benzaldehyde with as little as 0.05 mol% loading, quantitative conversion is achieved in 10 min at ambient temperature. Another salen catalyst - a bifunctional salen-phosphine oxide-Ti(IV) combination - promotes enantioselective cyanosilylation of aldehydes. Fine tweaking of the structure of another series of bifunctional chiral salen-Ti(IV) complexes allows the enantioselectivity to be reversed. Biaryl-bridged salen-titanium complexes are also highly efficient catalysts, one example giving 87% ee at room temperature. ... 

---