Illisimonin A was isolated from Illicium simonsii and has a previously unreported tricyclic carbon framework. It displayed neuroprotective effects against oxygen-glucose deprivation-induced cell injury in SH-SYSY cells. It incorporates a highly strained trans-pentalene ring system. We report the first synthesis of (+/-)-illisimonin A. Notable steps in the route include a 1,3-dioxa-2-silacyclohexene templated Diels-Alder cyclo-addition and type-3 semipinacol rearrangement to generate the trans-pentalene. The final step is an iron-catalyzed C-H oxidation. The synthetic route is robust, with 94 mg of racemic material prepared in a single pass. Resolving an intermediate enabled the synthesis of natural (-)-il-lisimonin A. The absolute configuration of (-)-illisimonin A was revised to 1S,4S,SS,6S,7R,9R,10R based on the X-ray structure of a heavy-atom analogue.