Tetramethyldihydroxanthenes constitute a large class of natural products wherein a 6-member ring triketone moiety is linked to an aromatic moiety. Progress toward the syntheses of six biologically active natural products isolated from these genus species; rhodomyrtone A, rhodomyrtosones A and B, tomentosones A and B, and bullataketals A and B, are described. These compounds possess challenging structures and interesting bioactivities making them attractive targets. Isolation, structure elucidation and biosyntheses of rhodomyrtone A, rhodomyrtosone A and B, tomentosones A and B, and bullataketals A and B are discussed. To accomplish their total syntheses, several new methodologies have been developed. A nickel-mediated catalytic 1,4-conjugate addition was developed. Literature precedents showcasing the use of nickel-mediated 1,4-conjugate addition and previously reported nickel-mediated enantioselective catalytic systems are presented herein along with our work. The challenges met during the development of a regioselective dehydrative cyclization for the syntheses of rhodomyrtone A and rhodomyrtosone B are discussed and strategies designed to overcome this synthetic challenge are presented in detail. Our studies to develop a flow photochemistry-mediated process to access endoperoxides, as well as generation and trapping of active vinyloxocarbenium intermediates are presented along with relevant literature precedents.