Commercially viable synthesis of cantharidin and bioactive cantharidin derivatives

A process comprising:

• a) providing a first compound of formula (1):
• wherein X is selected from the group consisting of S, O, CH2, CHR1, CR1R2, NH, NR1, and NR1R2, wherein said R1 and R2 are each independently selected from alkyl, aryl, heteroaryl, alkoxy, amine, alcohol, and halogen or together are a carbonyl, alkenyl, imine, or oxime, wherein said R1 and R2 are each optionally independently substituted;
• and
• b) forming a second compound having formula (2):
• wherein X is selected from the group consisting of S, O, CH2, CHR1, CR1R2, NH, NR1, and NR1R2, wherein said R1 and R2 are each independently selected from alkyl, aryl, heteroaryl, alkoxy, amine, alcohol, and halogen or together are a carbonyl, alkenyl, imine, or oxime, wherein said R1 and R2 are each optionally independently substituted;
• wherein said second compound is formed by reacting said first compound with furan in the presence of at least one Lewis acid selected from the group consisting of bis(cyclopentadienyl)zirconium(IV) bis(trifluoromethanesulfonate)tetrahydrofuran complex, bis(cyclopentadienyl)titanium(IV) bis(trifluoromethanesulfonate), and trimethylsilyl trifluoromethanesulfonate.