GENERAL METHOD FOR ASYMMETRIC SYNTHESIS OF SUBSTITUTED 2,2'-BIARYLDIOLS VIA ASYMMETRIC DESYMMETRIZATION OF 2,2',6,6'-TETRAHYDROXYBIPHENYL WITH L-MENTHONE

摘要

Asymmetric desymmetrization of prochiral 2,2',6,6'-biphenyltetrol by acetalization with l-menthone affords isomenthonide 5b of S-axial chirality. A variety of (S)-6,6'-dialkoxy-2,2'-biphenyldiols of high enantiomeric purities are synthesized by using 5b as an intermediate. Thus, etherification of the hydroxy groups of 5b followed by hydrolysis of the isomenthonide moiety give the corresponding 6,6'-dialkoxy-2,2'-biphenyldiols (12). Intermolecular cyclization of 5b with 1,omega-dibromoalkanes followed by hydrolysis yields 2,2'-biphenyldiols 13 with alkylenedioxy bridges at the 6 and 6' positions. Regioselective functionalization of 13 leading to 3,3'-dimethyl, -diphenyl, and -bis(TBS) derivatives is achieved either via directed lithiation of a carbamate derivative or via regioselective bromination reaction of 13. Origin of the stereoselectivity in acetalization reaction as well as thermal stability of the axial chirality of 2,2'-biphenyldiols is also discussed. (C) 1997 Elsevier Science Ltd. [References: 54]