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

Zhenjie Yang; Hong-Gang Cheng; Ruiming Chen; Liming Cao; Qiang Wei; Qingqing Wang; Qianghui Zhou

doi:10.1055/a-1799-0459

Synthesis, Table of Contents

Synthesis 2022; 54(21): 4691-4702
DOI: 10.1055/a-1799-0459

special topic

Asymmetric C–H Functionalization

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

Zhenjie Yang

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

,

Hong-Gang Cheng∗

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

,

Ruiming Chen

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

,

Liming Cao

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

,

Qiang Wei

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

,

Qingqing Wang

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

,

Qianghui Zhou∗

^aSauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Opto-Electronic Materials, College of Chemistry and Molecular Sciences, Wuhan University, 430072, Wuhan, P. R. of China

^bThe Institute for Advanced Studies, Wuhan University, 430072, Wuhan, P. R. of China

^cState Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, 345 Ling Ling Rd, Shanghai 200032, P. R. of China

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Abstract

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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

Full Text

References

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Supplementary Material

Supporting Information