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.

 

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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.

 

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Publication History

Article published online:
20 December 2024