Nondynamic and Dynamic Kinetic Resolution of Lactones with Stereogenic Centers and Axes: Stereoselective Total Synthesis of Herbertenediol and Mastigophorenes A and B

Abstract

The stereoselective total synthesis of the sesquiterpene herbertenediol (3) and of its naturally occurring dimers, mastigophorenes A [(P)-1] and B [(M)-1], is described. Following the “lactone concept”, the configuration at the biaryl axis was atropo-divergently induced to be P or, optionally, M, by stereocontrolled reductive ring cleavage (diastereomeric ratio up to 97:3) of the configurationally unstable joint biaryl lactone precursor 17 using the oxazaborolidine−borane system, through dynamic kinetic resolution. Mechanistic considerations of the lactone coupling suggested interference by a methoxy group next to the halogen substituent and led to an improvement of the coupling yield from 39 to 87% (to give the lactone 37). As a new, likewise highly efficient variant of the lactone method, we report for the first time thenow nondynamickinetic resolution of a structurally related, but centrochiral “aliphatic−aromatic” lactone, (rac)-10. Its highly efficient (krel > 300) enantiomer-differentiating Corey−Bakshi−Shibata reduction delivers the centrochiral building block (R,R)-10 in good chemical yield and with excellent stereochemical purity (enantiomeric excess > 99.9%; enrichment of the starting matrial). The new synthesis of natural herbertenediol (3) confirms its absolute stereostructure as well as that of its dimers, (P)-1 and (M)-1.