Cryogenic Organometallic Carbon-Fluoride Bond Functionalization with Broad Functional Group Tolerance
D Lucas Kane1, Bryan C Figula1, Kaluvu Balaraman1
1Georgetown University, Chemistry Department, Washington, D.C. 20057, United States.
Journal of the American Chemical Society
|February 6, 2025
Summary
This study introduces a novel method for functionalizing the robust carbon-fluorine (C-F) bond under mild cryogenic conditions. This breakthrough enables selective carbon-carbon bond formation using alkyl fluorides, previously challenging due to the C-F bond
Area of Science:
- Organic Chemistry
- Organometallic Chemistry
- Synthetic Chemistry
Background:
- Fluorinated organic compounds possess unique properties valuable in chemical and pharmaceutical sciences.
- The high stability of the carbon-fluorine (C-F) bond limits its synthetic utility compared to other alkyl halides.
- Existing methods for C-F bond functionalization are often limited in scope or require harsh conditions.
Purpose of the Study:
- To develop a practical and high-yielding method for functionalizing the Csp³-F bond under mild conditions.
- To achieve selective carbon-carbon bond formation with unactivated alkyl fluorides.
- To demonstrate the broad applicability and functional group tolerance of the new method.
Main Methods:
- Utilized cryogenic temperatures (as low as -78 °C) for Csp³-F bond cleavage.
- Employed fluorophilic organoaluminum compounds to activate the C-F bond.
- Leveraged fast nucleophile transfer of intermediate ate complexes for bond formation.
Main Results:
- Achieved practical and high-yielding functionalization of primary, secondary, and tertiary alkyl fluorides.
- Demonstrated exceptional chemoselectivity, tolerating a wide range of other functional groups.
- Successfully forged new carbon-carbon bonds via arylation, alkylation, alkenylation, and alkynylation reactions.
Conclusions:
- The developed method selectively targets the strong C-F bond, overcoming previous synthetic limitations.
- This approach offers a complementary strategy for late-stage functionalization, expanding synthetic possibilities.
- The stability of the Al-F bond serves as a key thermodynamic driver for the observed reactivity.
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