Cheng H.-G,
Yang Z,
Chen R,
Cao L,
Tong W.-Y,
Wei Q,
Wang Q,
Wu C,
Qu S,
*,
Zhou Q.
*
Wuhan University and Hunan University, Changsha, P. R. of China
A Concise Total Synthesis of (–)-Berkelic Acid.
Angew. Chem. Int. Ed. 2021;
DOI:
10.1002/anie.202014660
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.
