UC Irvine

Described in this dissertation work are the paths, dead-ends and detours involved in eventually securing an enantiospecific formal synthesis of (+)-7,20-diisocyanoadociane (DICA) via Corey’s dione, a project spanning early 2012 to early 2016. Highlighted is the isolation and biological background to DICA and isocyanoterpenes in general, in addition to the prior synthetic art for the preparation of cycloamphilectane and isocycloamphilectanes. Initial attempts at an entry into the DICA framework included a polyene cyclization, Diels–Alder/aldol condensation and reductive enone coupling strategy. Although these routes were unsuccessful they served as essential evolutionary precursors to the eventual completion of Corey’s dione. Efforts to utilize Swaminathans oxy-Cope/transannular Michael cascade to construct the perhydropyrene scaffold of DICA led to a structural reassignment. Further mechanistic investigations into this reaction elucidated that the transannular Michael reaction was in fact under kinetic control. A phenanthrenone reduction route led to an unexpected stereochemical outcome that could be useful for predictive control of either cis or trans outcomes. An enantiospecific formal synthesis of DICA was eventually secured through a dihydronaphthalene reduction. A general approach to multiple C7-isocyano(iso)cycloamphilectanes is also discussed.