Nondynamic and dynamic kinetic resolution of lactones with stereogenic centers and axes: Stereoselective total synthesis of herbertenediol and mastigophorenes A and B

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, b y 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. Mec hanistic 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, like wise highly efficient variant of the lactone method, we report for the firs t time, the-now nondynamic-kinetic resolution of a structurally related, bu t centrochiral "aliphatic-aromatic" lactone, (rac)-10. Its highly efficient (k(rel) > 300) enantiomer-differentiating Corey-Bakshi-Shibata reduction d elivers the centrochiral building block (R,R)-10 in good chemical yield and with excellent stereochemical purity (enantiomeric excess > 99.9%; enrichm ent of the starting matrial). The ew synthesis of natural herbertenediol (3 ) confirms its absolute stereostructure as well as that of its dimers, (P)- 1 and (M)-1.