Synthetic approaches to cularines. II: Ullmann condensation

The first total syntheses of O-methylcularicine 9b and sarcocapnine 9c are described together with a new synthesis of cularine 9a using the Ullmann condensation reaction of the appropriate 2′-bromo-8-hydroxy-tetrahydrobenzylisoquinoline formed by phase-transfer alkylation of Reissert compound 2. When this strategy was combined with the lead tetraacetate treatment of the tetrahydrobenzylisoquinoline it yielded 4-hydroxycularines, from which highly oxidized members of the family can be obtained. This is exemplified by the first synthesis of 4-hydroxysarcocapnine 19 and its transformation to the 3,4-dioxoisocularine yagonine 20, rearrangement of which afforded the aristoisocularine aristoyagonine 21.