High Yield Synthesis of Curcumin and Symmetric Curcuminoids: A Click and Unclick Chemistry Approach

The worldwide known and employed spice of Asian origin, turmeric, receives significant attention due to its numerous purported medicinal properties. Herein, we report an optimized synthesis of curcumin and symmetric curcuminoids of aromatic (bisdemethoxycurcumin) and heterocyclic type, with yields going from good to excellent using the cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF (ca. 95%). The subsequent cleavage of the BF2 group is of significant importance for achieving a high overall yield in this two-step procedure. Such cleavage occurs by treatment with hydrated alumina (Al2O3) or silica (SiO2) oxides, thus allowing the target heptanoids obtained in high yields as an amorphous powder to be filtered off directly from the reaction media. Furthermore, crystallization instead of chromatographic procedures provides a straightforward purification step. The ease and efficiency with which the present methodology can be applied to synthesizing the title compounds earns the terms click and unclick applied to describe particularly straightforward, efficient reactions. Furthermore, the methodology offers a simple, versatile, fast, and economical synthetic alternative for the obtention of curcumin (85% yield), bis-demethoxycurcumin (78% yield), and the symmetrical heterocyclic curcuminoids (80-92% yield), in pure form and excellent yields.

Automated summary

In this study, an optimized synthesis of curcumin and symmetric curcuminoids was reported. The use of a cyclic difluoro-boronate derivative of acetylacetone prepared by reaction of 2,4-pentanedione with boron trifluoride in THF resulted in good to excellent yields. Subsequent cleavage of the BF2 group using hydrated alumina or silica oxides allowed for the direct filtration of the target heptanoids in high yields. Furthermore, crystallization provided an efficient purification step. The present methodology offers a simple, versatile, fast, and economical synthetic alternative for obtaining curcumin, bis-demethoxycurcumin, and symmetrical heterocyclic curcuminoids in pure form and excellent yields.