Zhong L.-P,
Feng R,
Wang J.-J,
Li C.-C.
*
Southern University of Science and Technology, Shenzhen, P. R. of China
Asymmetric Total Synthesis of Twin Bufogargarizins A and B.
J. Am. Chem. Soc. 2023;
145: 2098-2103
DOI:
10.1021/jacs.2c13494
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.
