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Access to the Enantiopure Axially Chiral Cyclophane Isoplagiochin D through Atropo‐diastereoselective Heck Coupling
Author(s) -
Meidlinger Daniel,
Marx Lisa,
Bordeianu Catalina,
Choppin Sabine,
Colobert Françoise,
Speicher Andreas
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201803677
Subject(s) - enantiopure drug , cyclophane , heck reaction , chemistry , stereochemistry , combinatorial chemistry , molecule , enantioselective synthesis , organic chemistry , palladium , catalysis
Macrocyclization is typically the key step in the syntheses of cyclophane‐type natural products. Considering cyclophanes with axially chiral biaryl moieties, the control of atroposelectivity is essential with biological activity and is synthetically challenging. We report an atroposelective approach involving Heck cyclization, which for the first time enables the total synthesis of an enantiopure macrocyclic bis(bibenzyl), namely isoplagiochin D. An enantiopure sulfinyl auxiliary in the ortho position of a biaryl axis (still flexible) was used to induce an atropo‐diastereoselective Heck coupling (up to 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.