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Silver-Promoted Fluorination Reactions of α-Bromoamides
Satoshi Mizuta1, Kanami Kitamura1, Ayako Kitagawa1
1Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo, Nagasaki, 852-8521, Japan.
Abstract:
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 AgI is also demonstrated. Examples of reactions of α-bromoamides with O nucleophiles are presented.
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