Catalytic Enantioselective α-Fluorination of Ketones with CsF
Baocheng Wang1, Shuaixin Fan1, Chaoshen Zhang1
1Department of Chemistry and the Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstruction, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, 999077, Hong Kong SAR (China).
Abstract:
Disclosed here is a catalytic enantioselective nucleophilic α-fluorination of simple ketones. A new hydrogen bonding donor catalyst was designed to not only overcome the competing catalyst deactivation but also enable efficient enantiocontrol in C-F bond formation between racemic α-keto sulfoniums and CsF. Careful condition optimization resulted in a general and mild protocol applicable for the configurational flexible acyclic α-fluoro ketones bearing a tertiary stereogenic center, thus complementary to the previous electrophilic fluorination methods that were only effective to cyclic ketones and/or tetrasubstituted stereogenic centers. Preliminary mechanistic studies support a phase transfer and dynamic kinetic resolution pathway operated by HBD-enabled anion-binding.
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