Qiao J-B,
Meng L,
Pei J-Y,
Shao H,
Zhao Y-M.
*
Shaanxi Normal University, Xi’an, P. R. China
Total Synthesis of Ryanodane Diterpenoids Garajonone and 3-
epi-Garajonone.
Angew. Chem. Int. Ed. 2024;
DOI:
10.1002/anie.202417647
Keywords
(+)-garajonone - ryanodane diterpenoid - 1,2-addition - Babler–Dauben reaction - carbonylative
Heck reaction - Weitz–Scheffer epoxidation - Mukaiyama hydration
Significance
Zhao and co-workers report the synthesis of the ryanodane diterpenoid ( + )-garajonone
as well as its non-natural epimer 3-epi-garajonone. Key to the synthesis is a 1,2-addition and carbonylative Heck reaction
to construct the carbocycle of the natural product. From a common intermediate, both
( + )-garajonone and 3-epi-garajonone were accessed.
Comment
Allylic alcohol C was obtained through 1,2-addition of metalated arene B to enone A. Subsequent Babler–Dauben reaction gave rise to vinyl bromide D, which underwent a Pd-catalyzed carbonylative Heck reaction furnishing ester F. Upon debenzylation, ester hydrolysis, and phenol oxidation, dienone I was obtained. Weitz–Scheffer epoxidation of I was used to mask the bridging olefin and enable regioselective hydrogenation with
concomitant epoxide opening. The obtained alcohol was inverted through elimination
and Mukaiyama hydration furnishing tertiary alcohol K.
