Atroposelective Synthesis of Isoriccardin C through a C−H Activated Heck Type Macrocyclization

Macrocyclization is typically the key step in syntheses of cyclophane‐type natural products. Considering compounds with axially chiral biaryl moieties, the control of atroposelectivity is essential for biological activity and is synthetically challenging. Herein we report on atroposelective macrocyc...

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Bibliographic Details
Published in:European journal of organic chemistry 2021-03, Vol.2021 (9), p.1351-1354
Main Authors: Marx, Lisa, Lamberty, Daniel, Choppin, Sabine, Colobert, Françoise, Speicher, Andreas
Format: Article
Language:English
Subjects:
Atropisomerism
Biaryls
Biological activity
Chemical Sciences
C−H activation
Directing group
Natural cyclophanes
Natural products
Organic chemistry
Synthesis
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Summary:Macrocyclization is typically the key step in syntheses of cyclophane‐type natural products. Considering compounds with axially chiral biaryl moieties, the control of atroposelectivity is essential for biological activity and is synthetically challenging. Herein we report on atroposelective macrocyclization involving an oxidative Heck type process and enabling the first atropo‐enantiopure synthesis of isoriccardin C. A chiral sulfinyl auxiliary in the ortho‐position of a biaryl axis (still flexible) was used to induce a C−H activated atropodiastereoselective oxidative Heck coupling (>98 % de). The traceless character of the sulfinyl auxiliary enables the introduction of a hydroxy group to give the target molecule with >98 % ee as well. A chiral sulfinyl auxiliary group in ortho‐position of a biaryl axis is directing in the adjacent aryl moiety an atropo‐diastereoselective ortho’‐Fujiwara‐Moritani Heck coupling with dynamic kinetic resolution and can finally be transformed into a hydroxyl function of a natural occurring cyclophane type bisbibenzyl.
ISSN:1434-193X
1099-0690
DOI:10.1002/ejoc.202100017