Synthetic studies towards the mannolides: Construction of the bowl-shaped B/C/D ring system

Abstract

The bowl-shaped tricyclo[6.3.1.0 4,12 ]dodecane moiety is the core feature of cephalotane-type diterpenoids. As part of our efforts directed towards a total synthesis of mannolide B, the bowl-shaped tricyclo[6.3.1.0 4,12 ]dodecane skeleton, a common intermediate of cephalotane-type diterpenoids bearing up to five contiguous stereocenters including two quaternary carbon centers had been constructed. The synthetic strategy was enabled by an efficient application of oxidative dearomatization/intramolecular Diels-Alder reaction to access highly functionalized building block with the tricyclo[5.2.2.0 2,6 ]undecane unit from commercially available materials. The key feature was firstly used the cyclic olefins with secondary alcohol as dienophile for the intramolecular inverse electron demand Diels-Alder reaction. Further synthetic studies led to construct ring D by a regioselective Aldol reaction. • Construction of the common core of cephalotane-type diterpenoids. • Decarboxylative aromatization facilitates polysubstituted phenol synthesis. • Oxidative dearomatization/Diels-Alder reaction constructs congested rings.