Synthesis of (+)-Asteriscanolide

Key words

(+)-asteriscanolide - [4+4] cycloaddition - Brinkmeyer reduction - Claisen rearrangement - cyclooctadiene synthesis - hydroalumination - Swern oxidation

Significance

Wender and co-workers report the first total synthesis of sesquiterpinoid lactone (+)‑asteriscanolide. Key to their approach is a nickel-catalyzed [4+4]-cycloaddition methodology, which was developed in their group. They successfully establish the first asymmetric synthesis of a cyclooctane-containing terpenoid.

Comment

The synthesis commences with construction of acid F through a Claisen rearrangement. Asymmetric Brinkmeyer reduction of ketone H with LAH in presence of Darvon alcohol (I) as a chiral ligand gives rise to J with excellent enantioselectivity. Tetraene M was accessed by a hydroalumination stannylation sequence followed by lithiation and carboxylation. The key nickel-catalyzed intramolecular [4+4] cycloaddition forged cyclooctadiene N.

Publication History

Article published online:
16 August 2023