Total Synthesis of (+)-Garajonone

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.

Publication History

Article published online:
20 December 2024