Synthetic radical chemistry. Total synthesis of (±)-isoamijiol

Abstract

A total synthesis of the dolastane diterpene (±)-isoamijiol (1), found in the brown seaweed Dictyota linearis, is described. The synthesis, which starts from cyclopentanone, uses just seven carbon-to-carbon bond forming reactions, four of which involve free radical intermediates. The 5,7-ring fused (azulene) portion in (1) was elaborated by an intramolecular [2 + 2]-photocycloaddition [viz. (16)→(17)]–intermolecular reductive coupling [viz. (17c)→(29)]–cyclobutane fragmentation [viz. (29)→(15)] sequence, and the 6-ring in compound (1) was annulated via intramolecular reductive coupling of the terminal acetylenic ketone intermediate (14)[to the tricycle (38)]. Oxidation of compound (38), using catalytic selenium dioxide in the presence of t-butyl hydroperoxide, then produced (±)-isoamijiol which showed spectral data identical with naturally derived material.