Total Synthesis of (–)-Berkelic Acid

Key words

(–)-berkelic acid - Catellani reaction - oxa-Michael reaction - nickel catalysis - reductive coupling

Significance

Qu, Zhou, and co-workers report a concise total synthesis of (–)-berkelic acid, which was isolated in 2006 from an extremophilic Penicillium species. Their synthesis relies on a Catellani ­reaction followed by an oxa-Michael addition performed in a one-pot operation and a late-stage Ni-catalyzed reductive coupling.

Comment

The synthesis commences with the preparation of enone B, which is accessed from ­ketone A in four steps. A Catellani reaction/oxa-­Michael cascade gives rise to F. Benzyl deprotection followed by spiroacetalization gives ketal G in good yield and excellent diastereoselectivity, setting four stereocenters from only one existing chiral center. Iodide H is then coupled with acid chloride J in a Ni-catalyzed reductive coupling to give methyl ester K. (–)-Berkelic acid is obtained by selective saponification in the presence of (Bu₃Sn)₂O.

Publication History

Article published online:
16 February 2021