Terpenoids to Terpenoids: Enantioselective Construction of 5,6-, 5,7-, and 5,8-Fused Bicyclic Systems. Application to the Total Synthesis of Isodaucane Sesquiterpenes and Dolastane Diterpenes

Abstract

The prevalence of a C12 common core (10) in C15-C30 terpenoids has been recognized. Construction of two “chirons” ((−)-11 and (−)-12a,b), corresponding to 10, from abundantly available ((R)-(+)-limonene has been achieved through diastereoselective [3s.3s] sigmatropic processes 16 → 11 and 19 → 12, respectively. Chirons 11 and 12 have been successfully annulated to bicyclic hydrindanones 21, 23, and 30, hydrazulenoids 31–33, and 5,8-fused system 42 through methodologies that are short and practical. Thus, these enantiomerically pure bicyclics are available as advanced building blocks for higher terpene synthesis. One of the hydrazulenoids ((−)-31) has been elaborated to isodaucane sesquiterpenes (+)-aphanamol I (2) and (+)-2-oxoisodauc-5-en-12-al (46) through a novel restructuring protocol (31 50). The stereo- and enantioselective synthesis reported here has established the absolute stereochemistry of isodaucane sesquiterpenes. The hydrazulenoid (−)-31 has also been deployed for the first enantioselective synthesis of oxygenated dolastane diterpenes (+)-isoamijiol (63) and (+)-dolasta-l(15),7,9-trien-14-ol (64). The key step in this venture was the stereoselective annulation of a six-membered ring through radical-induced alkyne-carbonyl cyclization (67 → 68). © 1991, American Chemical Society. All rights reserved.