Chiral non racemic C2-symmetric biphenyls by desymmetrization of 6,6',2,2'-tetramethoxy-1,1'-biphenyls

Regioselective bromination of the title biphenyl 1 at the 3 and 3% positions and simultaneous desymmetrization of the biphenyl has been achieved. Metal-halide exchange at the 3,3% positions facilitated the introduction of functional groups in good yield. Regioselective reduction was obtained by using (CH3)3SiI, L-Selectride and HI according to the functional groups on the biphenyls. Resolution of 6,6%,2,2%-tetramethoxy-3,3%-dimethyl-1,1%-biphenyl 3 was achieved by its conversion to the corresponding phosphorothioamidate diastereomers of the (S)-(-)-a-methylbenzylamine. The absolute configuration of (M)-(+)-3 was confirmed by X-ray analysis of the corresponding diastereomer.