Synthesis of the Troponoid Natural Product Nezukone Via Sequential Rearrangement of Two Isomeric Precursors

Abstract

Nezukone (1) has been synthesized in seven steps from the readily available Δ³-trinorcarene (4). Key features of the sequence used include formation of the bicyclic isomer (2) of compound (1). Base-promoted isomerization of compound (2) followed by acidic workup then produced the isolable but highly unstable heptafulvenol (3), an extended enolic tautomer of nezukone (1). Under mildly basic conditions compound (3) rearranged to give the natural product (1). The X-ray crystal structure of the ring-fused cyclobutanone (8) is reported.