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Silver‐Promoted Fluorination Reactions of α‐Bromoamides
Author(s) -
Mizuta Satoshi,
Kitamura Kanami,
Kitagawa Ayako,
Yamaguchi Tomoko,
Ishikawa Takeshi
Publication year - 2021
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.202004769
Subject(s) - chemistry , nucleophile , steric effects , amide , alkyl , primary (astronomy) , stereospecificity , medicinal chemistry , fluoride , proton , functional group , kinetics , nucleophilic addition , leaving group , organic chemistry , catalysis , inorganic chemistry , physics , polymer , quantum mechanics , astronomy
Silver‐promoted C−F bond formation in α‐bromoamides by using AgF under mild conditions is reported. This simple method enables access to tertiary, secondary, and primary alkyl fluorides involving biomolecular scaffolds. This transformation is applicable to primary and secondary amides and shows broad functional‐group tolerance. Kinetics experiments revealed that the reaction rate increased in the order of 3°>2°>1° α‐carbon atom. In addition, it was found that the acidic amide proton plays an important role in accelerating the reaction. Mechanistic studies suggested generation of an aziridinone intermediate that undergoes subsequent nucleophilic addition to form the C−F bond with stereospecificity (i.e., retention of configuration). The synthesis of sterically hindered alcohols and ethers by using Ag I is also demonstrated. Examples of reactions of α‐bromoamides with O nucleophiles are presented.