Total Synthesis of (+)-Bufogargarizin B

Key words

(+)-bufogargarizin B - [5+2] cycloaddition - Mukaiyama hydration - retro-aldol-aldol reaction - Suzuki–Miyaura coupling

Significance

Li and co-workers report the total synthesis of the abeo-steroid (+)‑bufogargarizin B from commercially available sitolactone (A). Their synthetic strategy features a Ru-catalyzed [5+2] cycloaddition to forge the seven-membered ring. This transformation, which was pioneered by Wender and Trost, was adopted by the authors to convert silyl enol ether cyclopropane-ynes into cyclohept-3-en-1-ones.

Comment

Ketone B is converted into the silyl enol ether, which in situ undergoes the [5+2] cycloaddition. Retro-aldol-aldol reaction mediated by DBU in refluxing THF rearranges the carbon skeleton to F under high diastereocontrol. The 2‑pyrone moiety is installed by a Suzuki–Miyaura coupling of enol triflate G with boronic ester H. After seven consecutive operations, (+)‑bufogargarizin B is obtained. The authors also report the total synthesis of (–)-bufogargarizin A using ketone D as a common intermediate.

Publication History

Article published online:
17 March 2023