A sulfur-based strategy for synthesis of otonecine is described. Key steps include the thio-Diels-Alder trapping of thioketone 8 by the Danishefsky diene, followed by conversion into the enone 27 and internal Michael addition to afford bicyclic thioaminal 28. Selective C-S bond cleavage was achieved after conversion to alcohol 36 or its derivatives 38, resulting in the azocine ring system. The successful route proceeded from 40b via 49a and sulfoxide elimination to the alkene 50a. The final conversions to otonecine were accomplished via low-temperature osmylation of 56, a crucial OsO4-mediated oxidation of diol 58 to ketol 60/61, and Burgess elimination to 68/69. Several of the intermediates in late stages of the synthesis exist largely in the bicyclic valence bond tautomer form that is characteristic of the otonecine ring system.