Synthetic Study of Biologically Active Chiral Biaryls for Drug

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Axially chiral biaryls are significantly important not only as chiral ligands or auxiliaries in asymmetric reactions but also for biologically active natural products. For the asymmetric synthesis of axially chiral biaryls, we have investigated the cross-coupling of the planar chiral arylhalide chromium tricarbonyl complexes with arylboronic acids. Thus, palladium (0)-mediated Suzuki-Miyaura cross-coupling of planar chiral (2, 6-disubstituted bromobenzene) chromium complexes with o-substituted arylboronic acids gave stereoselectively axially chiral mono Cr(CO)3-complexed biaryls. The axial stereochemistry of the cross-coupling products was found to be largely dependent on the steric bulkiness of ortho substituent of arylboronic acids and reaction conditions. The overall process gives a promising approach for the preparation of both atropisomers stereoselectively starting from a single planar chiral (arene)chromium complex. By utilizing these methodologies, biologically active axially chiral natural products, steganone, korupensamine and axially chiral A-B ring system of vancomycin were stereoselectively synthesized.