Asymmetric Total Synthesis of 7-Isocyanoisocycloamphilect-14-ene and 7,15-Diisocyanoadociane

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Herein we report the first asymmetric total synthesis of the antimalarial natural products 7-isocyanoisocycloamphilect-14-ene (7-ICA-14-ene, 2) and 7,15-diisocyanoadociane (7,15-DICA, 3). The densely stereodefined tetracyclic skeletons of these targets are efficiently constructed via two transformations, a bispyrrolidine diboronate (BPDB)-catalyzed intermolecular exo-selective asymmetric Diels–Alder reaction, which constructs the central cyclohexane ring embedded with four contiguous stereocenters in a single stereocontrolled operation, and a visible-light-induced bis(catecholato)diborane-mediated aerobic 1,2-carbohydroxylation cascade to concurrently forge C–C and C–O bonds, enabling precise regio- and stereoselective construction of the trans-fused tetracyclic framework. This efficient synthetic route enables rapid access to this family of bioactive metabolites and demonstrates the power of asymmetric cycloaddition and photoredox radical cascade chemistry in constructing architecturally intricate polycyclic scaffolds.