One Intermediate, Many Fates: Divergent Synthesis from Tricarbonylmethane Scaffolds

Tricarbonylmethane scaffolds (1,2)¹ are privileged structural-motifs found in natural products, valuable synthetic-intermediates, and numerous bioactive-compounds exhibiting antibacterial, antifungal, antiparasitic, anticancer, and anti-inflammatory activities. Their remarkable reactivity also enables the construction of structurally-diverse molecular frameworks with potential applications in medicinal chemistry.^2-4 Herein, we report a divergent synthetic-platform that converts cyclic-1,3-diones (A, 5 starting-materials) into distinct families of tricarbonylmethane-derivatives. α-Hydroxymethylene- or α-methoxymethylene-1,3-diones (R₁ = HO or CH₃O, B, 10 compounds) were prepared as key intermediates and selectively transformed into α-aminomethylene-1,3-diones (C, 40 compounds, e.g., 3, bottom-left of GA) or dihydroquinazolinones (C, 5 compounds, e.g. 4, bottom-center in GA) through 8 complementary synthetic strategies depending on the reagents and the desired products.¹ This approach afforded 55 compounds, including 20 previously-undescribed derivatives, demonstrating broad substrate scope and functional-group tolerance.¹  These results establish tricarbonylmethane derivatives as valuable entry-points for diversity-oriented-synthesis and as a practical platform for constructing structurally varied compounds of synthetic and biological interest.