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Three‐Step Total Synthesis of Ramelteon via a Catellani Strategy
Author(s) -
Gao Shijun,
Qian Guangyin,
Tang Hao,
Yang Zuo,
Zhou Qianghui
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201901355
Subject(s) - chemistry , reductive amination , combinatorial chemistry , total synthesis , aldehyde , amide , alkylation , agonist , amination , organic chemistry , stereochemistry , catalysis , receptor , biochemistry
Ramelteon is the first medicine in human history that treat insomnia as a melatonin receptor agonist. Herein, we report an efficient three‐step synthetic route to access it from commercially available 2,3‐dihydrobenzofuran‐4‐amine, which represents as the shortest racemic synthesis to date with a 26 % overall yield. Key to the success is the application of the intermolecular Catellani‐type alkylation and intramolecular redox‐relay Heck cyclization cascade for preparation of the key indane‐containing aldehyde. The unique primary amide‐involved reductive amination of aldehyde is another feature of this route. New process of ramelteon can be developed based on this chemistry.