Alcohol to Fluoro / Carbonyl to Difluoro using Deoxofluor (BAST)

Reaction, Reagents
& Mechanism

Reaction & Reagents info

Deoxofluor or BAST [N,N-Bis(2-methoxyethyl)aminosulfur trifluoride]:

  • Deoxofluor or BAST [N,N-bis(2-methoxyethyl)aminosulfur trifluoride], is a nucleophilic fluorinating agent, similar to DAST
  • However, Deoxofluor is more thermally stable than DAST and also results in higher yields.
  • Deoxofluor or BAST, (N,N-bis(2-methoxyethyl)aminosulfur trifluoride, is a nucleophilic fluorinating agent, similar to DAST
  • Deoxofluor reacts with water violently, releasing highly corrosive HF gas. Hence, all operations of Deoxofluor is to be handled in dry atmosphere, with appropriate PPE

Advantages:

  • It is more thermally stable and hence large-scale reactions could be performed and reported in literature

Disadvantages:

  • Deoxofluor reacts with water violently, releasing highly corrosive HF gas
  • Deoxofluor is required in excess amounts (usually 3 eq. is used)

Deoxofluor or BAST – Functional Group Conversions

Sulfur-based Deoxyfluorinating reagents

  • Stable Fluorinating Reagent with Ease of Handling (FLUOLEAD®) – A safer substitute for DAST

Useful Links on Reagent & Reaction:


For review papers and other articles, 
refer to the tab "References"

Mechanism

Additional details

Scheme & Procedure

General Procedure:

To a solution of alcohol or carbonyl compound (1 eq.) in anhydrous dichloromethane (20 Vol) is added Deoxofluor (3 eq.) dropwise at –0 oC under nitrogen atmosphere and stirred at room temperature for overnight. The reaction is monitored by TLC. The reaction mxture is quenched with saturated solution of NaHCO3 and extracted with dichloromethane two times. The combined organic layer is successively washed with water (10 Vol x 2) and brine solution (5 Vol), dried over sodium sulphate, filtered and concentrated under reduced pressure. The crude product is purified by column chromatography.

Note:

  • The most preferable solvent is DCM. The addition of Deoxo is usually done at 0 oC and the reaction continued at RT.
  • Deoxofluor or BAST, (N,N-bis(2-methoxyethyl)aminosulfur trifluoride, is a nucleophilic fluorinating agent,
  • Deoxofluor is more thermally stable fluorinating agent, unlike DAST
  • Deoxofluor reacts with water violently, releasing highly corrosive HF gas. Hence, all operations of Deoxofluor is to be handled in dry atmosphere, with appropriate PPE

Safer alternative to Deoxofluor:

  • Stable Fluorinating Reagent with Ease of Handling (FLUOLEAD®) – A safer substitute for DAST

For more details on reactions and reagents, 
refer to the tab "Reaction, Reagents and Mechanism"

Typical Procedure:

For more details on large-scale reactions and OPRD procedures, 
refer to the tab "Scale-up & Green Chem"

WO2016011390, page No. 382 (to change)

Scale-up &
Green Chem.

Deoxofluor has been used on large scale reactions and several OPRD articles have been reported

  • Deoxy-Fluor or BAST recations have been performed in Hastelloy C 276 equipment, as HF is generated during the reaction (Ref: OPRD, 2010, 14, 623–631)

Safer alternatives to Deoxofluor:

  • Stable Fluorinating Reagent with Ease of Handling (FLUOLEAD®) – A safer substitute for DAST

Scale-Up Typical Procedure:

Green Chemistry Aspects:

Reaction Tree

References

Deoxofluor – References:

General Fluorination – References:

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