摘要：Department of Chemistry and the Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstr

转自：康龙化成

Catalytic Enantioselective α‑Fluorination of Ketones with CsF

Baocheng Wang, Shuaixin Fan,Chaoshen Zhang,* and Jianwei Sun*

Department 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, Kowloon 999077, Hong Kong SAR (China)

—J. Am. Chem. Soc., 2025, 147, 12, 10059–10065.

Recommended by Shi Li_MOC

KEYWORDS: Fluorination,asymmetric synthesis, organocatalysis, (反应类型), ketones, CsF (原料), α-fluoro ketones (产物), C(sp3)–F (成键类型), chiral HBD catalyst(其他)

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 Hydrogen bond donor (HBD)-enabled anion-binding.

Introduction

Condition Optimization

Synthetic scope

Proposed mechanism

C. Zhang, J. Sun and co-workers developed a catalytic enantioselective nucleophilic α-fluorination of ketones from sulfonium salts and CsF. This protocol is efficient for generating acyclic α-fluoro ketones bearing a tertiary stereogenic center, despite their configurational flexibility and labile chirality. A range of α-keto sulfonium salts participated smoothly in the stereocontrolled C−F bond formation with CsFunder mild conditions, furnishing diverse α-fluoro ketones with high efficiency and enantioselectivity. The products generated from our process are useful precursors to other valuable chiral fluorine molecules. Thisprotocol allowed for variation of the sulfaneleaving group to serve as an additional handle to tune enantioselectivity. Preliminary mechanistic studies support a phase transfer and dynamic kinetic resolution pathway operated by HBD-enabled anion binding.

来源：新浪财经