Towards the rubromycins: An efficient synthesis of a suitable isocoumarin precursor, its lactam analogue, and palladium-catalyzed couplings

6-Iodoisocoumarin 4 and its aza-analogue, 6-iodo-I-oxo-isoquinoline 29, were efficiently prepared from vanillin in seven and six steps, respectively. Key transformations in their syntheses were achieved by directed ortho-lithiation and variations of Horner-Wadsworth-Emmons reactions. Both 6-Iodoisocoumarin 4 and its aza-analogue were designed for insertion into syntheses of rubromycin type target structures via palladium-catalyzed coupling reactions. For the isocoumarin subunit, this plan could be confirmed through Heck, Sonogashira, and Suzuki reactions of our building block with various substrates.