Abstract
<jats:p>A concise 11-step total synthesis of roussoellatide is disclosed. This structurally unprecedented marine fungal metabolite, characterized by the unusual linkage of a dichlorinated cyclopentenone and a densely functionalized cyclohexene, was assembled in a highly convergent manner. Strategic recognition of hidden symmetry in the cyclohexenyl domain, combined with a redox-neutral Ni-catalyzed radical cross-coupling (RCC) of a meso-diene with an aromatic fragment, enabled rapid construction of the core skeleton while establishing the relative configuration of all key stereocenters. Subsequent chemoselective operations—including a challenging arene perchlorination, diester differentiation, Julia–Kocienski olefination, and a biomimetic oxidative ring contraction—completed the synthesis with minimal protecting group manipulations. A simple resolution of the hydrazine adduct further delivered enantioenriched material, with efficient recycling of the undesired enantiomer. The route highlights the power of radical-based fragment coupling in overcoming electronic and steric barriers in complex natural product synthesis.</jats:p>