A versatile synthetic protocol involving the room temperature direct arylation of benzothiazole with a wide variety of iodoarenes under Ag-promoted Pd-catalyzed conditions in HFIP as the reaction solvent has been presented. A sequential HFIP-promoted selective iodination of arenes followed by Pd-catalyzed direct arylation of benzothiazole has also been disclosed. The utility of the developed protocol has been demonstrated by the synthesis of anti-tumor agents, PMX-610 and CJM-126 (precursor).