Eight-Step Asymmetric Synthesis of (–)-Berkelic Acid

Abstract

We herein report an eight-step asymmetric synthesis of (–)-berkelic acid. This work features a sequential Catellani-type reaction/oxa-Michael addition with epoxides as dual-functionalized alkylating reagents for synthesizing the isochroman framework, a one-pot, acid-catalyzed deprotection/spiroacetalization process for the construction of a tetracyclic core intermediate, and a late-stage Ni-catalyzed reductive coupling reaction for the installation of the side chain. Remarkably, during the deprotection/spiroacetalization process, four new stereocenters are created with high stereocontrol from a single existing chiral center.

Key words

(–)-berkelic acid - total synthesis - Catellani reaction - C–H activation - spiroacetalization - reductive coupling

Publication History

Received: 25 February 2022

Accepted after revision: 15 March 2022

Accepted Manuscript online:
15 March 2022

Article published online:
19 May 2022

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