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A General Catalytic Method for Highly Cost‐ and Atom‐Efficient Nucleophilic Substitutions
Author(s) -
Huy Peter H.,
Filbrich Isabel
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800588
Subject(s) - chemistry , catalysis , stereoselectivity , combinatorial chemistry , alkyl , halogen , nucleophile , organic chemistry
A general formamide‐catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT‐mediated dihydroxychlorination of an OH‐containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E‐factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional‐group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one‐pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold S N 2 inversion, which demonstrates the high practical value of the presented method.