Methods for the construction of linear 1,7-diarylheptanoids; synthesis of di-O-methylcentrolobol and precursors (synthetic and biosynthetic) to the meta,meta-bridged biphenyls myricanol and myricanone

1,7-Diarylheptanoids area varied natural product class in which ‘linear’ types [e.g. (1), (2), and (7)] appear to be biosynthetic precursors to macro(carbo)cyclic (3), macro(oxa)cyclic (4), and condensed polycyclic (5) examples. Various methods (suitable for radiolabelling) are described for constructing ‘linear’ diarylheptanoids, including Grignard couplings (employing activated magnesium) with arylpropanals and oxazonium salts [(9e), (14d), (14h)+(10), (17)→(11a), (11h), (15a), and (15b)] and dithian alkylation [(19a)+(14e)→(15c)]. Alkyllithium treatment of the benzyloxydithian (19b) gave 1,2,3-triphenylcyclopropane. Syntheses via trialkylcyanoborates were frustrated by disproportionation of the intermediate trialkylboranes. The diarylheptanoids synthesised (11a–h) and (15a–e) include synthetic and biosynthetic precursors to meta,meta-bridged biphenyls and related macrocyclic ethers.