INTRAMOLECULAR REGIOSELECTIVE INSERTION INTO UNACTIVATED PROCHIRAL CARBON-HYDROGEN BONDS WITH DIAZOACETATES OF PRIMARY ALCOHOLS CATALYZED BY CHIRAL DIRHODIUM(II) CARBOXAMIDATES - HIGHLY ENANTIOSELECTIVE TOTAL SYNTHESIS OF NATURAL LIGNAN LACTONES

Intramolecular insertion into unactivated prochiral C-H bonds of 3-ary l-1-propyl diazoacetates catalyzed by dirhodium(II) tetrakis[methyl 1- (3-phenyl propanoyl)imidazolidin-2-one-4(R or S)-carboxylate], Rh-2(4R -MPPIM)(4) or Rh-2(4S-MPPIM)(4), occurs in 91-96% ee and with virtuall y complete regiocontrol for the formation of beta-benzyl-gamma-butyrol actones. This methodology has been applied to the total synthesis of d ibenzylbutyrolactone lignans (-)- and (+)-enterolactone, (-)- and (+)- hinokinin, and (+)-arctigenin from substituted cinnamic acids in 19-27 % overall yields. Aryltetralin lignan (+)-isodeoxypodophyllotoxin was prepared from the reactant 3,4-(methylenedioxy)cinnamic acid in 36% yi eld overall, and the lactone precursor to (+)-isolauricerisinol was fo rmed in 96.5% ee and 23% yield overall. Applications of the chiral Rh- 2(MPPIM)4 catalysts to fully aliphatic systems resulting in the format ion of beta-substituted-gamma-butyrolactones with high regiocontrol an d with 93-96% ee have demonstrated the generality of this methodology. A model that provides accurate predictions of beta-substituted-gamma- butyrolactone absolute configurations in these asymmetric metal carben e transformations is described.