CAS: 38078-09-0 | Formula: C4H10F3NS | MW: 161.19 g/mol
Category: Fluorinated Building Blocks
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What Is DAST and How Does It Convert Alcohols to Alkyl Fluorides?
DAST (CAS 38078-09-0) is a bench-stable deoxofluorination reagent that converts alcohols to alkyl fluorides with predictable stereochemical outcomes. With a molecular weight of 161.19 g/mol and the formula C4H10F3NS, bp 30-32 °C at 3 mmHg, density 1.22 g/mL at 25 °C [001][002].
The global market for this category of chemicals continues to grow, driven by demand from pharmaceutical R&D, agrochemical development, and materials science applications [003].
How Does DAST Compare to Deoxo-Fluor and Other Fluorinating Agents?
The fluorination mechanism proceeds through a two-step SN2-type pathway. The alcohol first displaces fluoride from DAST to form an alkoxyaminosulfur difluoride intermediate, releasing HF. In the rate-determining second step, fluoride (from HF or another DAST molecule) attacks the α-carbon of the alkoxy group, displacing the aminosulfinyl fluoride leaving group with inversion of configuration [001]. Secondary alcohols with good leaving group ability (benzylic, allylic, propargylic) give the highest yields (>80%), while unactivated secondary alcohols often require elevated temperatures and give more elimination [002].
What Substrates Are Compatible with DAST-Mediated Fluorination?
The physical properties of DAST dictate its handling protocol. As a moisture-sensitive liquid that fumes in air and decomposes exothermically above 90 °C, it must be stored under inert atmosphere (argon or nitrogen) at 2-8 °C [001]. The reagent is typically dispensed by syringe or cannula transfer under positive argon pressure. Glass syringes with Teflon-tipped plungers are recommended, as DAST attacks standard rubber plunger tips over time [002].
What Safety Precautions Are Essential When Handling DAST?
In radiochemistry, DAST has been adapted for ¹⁸F-labeling of PET (positron emission tomography) tracers. The ¹⁸F-DAST protocol enables nucleophilic ¹⁸F-fluorination of aliphatic alcohols with radiochemical yields of 10-40% and specific activities exceeding 50 GBq/μmol [001]. In medicinal chemistry, installing a single fluorine atom at a metabolically labile position using DAST is a standard strategy to block cytochrome P450 oxidation and extend the half-life of drug candidates [002].
How Can Common DAST Side Reactions Be Minimized?
The safety profile of DAST demands rigorous protocols. Upon contact with water, it releases HF gas — a deep-tissue penetrator that causes delayed, extremely painful burns [001]. All workstations must have calcium gluconate gel (2.5%) immediately accessible. DAST must be stored in a dedicated, clearly labeled secondary container within a flammable storage cabinet, separate from aqueous reagents, alcohols, and bases [002].
FAQ
Q: Why does DAST sometimes cause elimination instead of fluorination?
A: Elimination competes with substitution when the alcohol substrate has β-hydrogens and forms a stable carbocation intermediate. Tertiary and benzylic alcohols are particularly prone to elimination. Strategies to minimize this include: using DAST at -78 °C with slow warming, switching to Deoxo-Fluor (less acidic byproducts), or converting the alcohol to a better leaving group (mesylate/tosylate) before fluorination.
Q: What is the difference between DAST and Morpho-DAST?
A: Morpho-DAST (bis(2-methoxyethyl)aminosulfur trifluoride) replaces the diethylamino group with a bis(2-methoxyethyl)amino moiety. It is significantly more thermally stable than DAST (onset of decomposition ~140 °C vs ~90 °C) and produces fewer elimination byproducts with sensitive substrates. However, it is 2-3× more expensive and the byproducts are harder to remove by aqueous workup.
Q: Can DAST fluorinate carbonyl compounds?
A: Yes, DAST converts aldehydes and ketones to gem-difluorides (CF2 groups). The reaction proceeds through the same fluoro-sulfurane intermediate, but requires longer reaction times (12-24 hours at room temperature) and often catalytic amounts of HF or BF3·OEt2 to accelerate the conversion. Unactivated ketones may require DAST in refluxing DCM or 1,2-dichloroethane.
Q: How should DAST waste be quenched safely?
A: DAST reacts violently with water, generating HF. Quenching must be done by slow addition of the reaction mixture to ice-cold saturated NaHCO3 solution (NOT the reverse). The aqueous layer should be tested with pH paper before disposal — it must be alkaline (pH >8) to ensure all HF has been neutralized. Calcium gluconate gel should be available as an HF antidote at all workstations where DAST is used.
Key Statistics at a Glance
| Metric | Value | Source |
|---|---|---|
| Molecular Weight | 161.19 g/mol | |
| Boiling Point | 30-32 °C at 3 mmHg | |
| Density | 1.22 g/mL at 25 °C | |
| Formula | C4H10F3NS | |
| Decomposition Onset | ~90 °C | |
| Typical Reaction Temperature | -78 °C to 25 °C |
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Availability at CoreyChem: This product is not currently listed in CoreyChem's standard catalog.
The Role of DAST in PET Radiochemistry
Positron emission tomography (PET) imaging relies on ¹⁸F-labeled tracers with a 109.8-minute half-life, requiring rapid, high-yielding fluorination chemistry that can be completed within 2-3 half-lives [001]. DAST has been adapted for ¹⁸F-fluorination through the 'cold DAST, hot fluoride' strategy: non-radioactive DAST is pre-mixed with the alcohol substrate, and cyclotron-produced [¹⁸F]fluoride (as K[¹⁸F]F/K222 complex) is added to initiate the fluorination.
The sequence of events — fluoride activation (azeotropic drying with MeCN), DAST-mediated fluorination (5-15 min at 70-90 °C), HPLC purification, and formulation — must be completed in <60 minutes from end of bombardment (EOB) to patient injection [002]. Radiochemical yields of 15-40% (decay-corrected) and radiochemical purity >99% are achievable for model substrates.
Beyond PET, DAST has found niche applications in the synthesis of trifluoromethyl ethers (ROCX3) — increasingly important functional groups in agrochemicals (fluxapyroxad, fluopyram) and pharmaceuticals. The O-CF3 group combines the metabolic stability of fluorine with the conformational properties of an ether linkage, often improving both potency and pharmacokinetics simultaneously [001].
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DAST Alternatives: Deoxo-Fluor, XtalFluor, and Beyond
The safety limitations of DAST (thermal instability, violent hydrolysis) have driven the development of alternative deoxofluorination reagents [001]:
Deoxo-Fluor (Bis(2-methoxyethyl)aminosulfur Trifluoride). Decomposes at ~140 °C (vs ~90 °C for DAST), enabling reactions at higher temperatures and shorter times. The 2-methoxyethyl byproducts are water-soluble and easily removed by aqueous workup. Deoxo-Fluor has largely supplanted DAST in process chemistry applications due to its superior safety profile, though it costs 2-3× more [002].
XtalFluor-E and XtalFluor-M. These crystalline (aminosulfur trifluoride) reagents offer the convenience of a solid with reactivity comparable to DAST. XtalFluor-E (diethylaminodifluorosulfinium tetrafluoroborate) requires an exogenous fluoride source (Et3N·3HF or DBU·HF), while XtalFluor-M (morpholino analog) incorporates an internal fluoride donor. Both reagents are bench-stable solids for months when stored under argon at room temperature [001].
PyFluor and PhenoFluor. These N-tosyl-4-chlorobenzenesulfonimidoyl fluoride reagents developed by the Doyle group enable deoxyfluorination of alcohols through a different mechanism (sulfonimidate formation followed by fluoride displacement). They offer excellent functional group tolerance and are air-stable solids, though the cost (~USD 200-500/g) limits them to small-scale applications [002].
Glycosyl Fluoride Synthesis with DAST
DAST-mediated fluorination of protected carbohydrates provides glycosyl fluorides — versatile glycosyl donors for oligosaccharide synthesis [001]. The reaction of peracetylated or perbenzylated hemiacetals with DAST in THF or DCM at 0 °C to room temperature gives the corresponding glycosyl fluorides with retention or inversion of anomeric configuration depending on substrate structure, protecting group pattern, and reaction conditions:
- α-Configured Hemiacetals: Perbenzylated pyranoses with an axial anomeric hydroxyl (manno, talo configuration) give β-fluorides via SN2 displacement with 70-90% yield.
- β-Configured Hemiacetals: Perbenzylated pyranoses with an equatorial anomeric hydroxyl (gluco, galacto configuration) give α-fluorides as the major product, though the stereoselectivity is more variable (50-80% α) due to competing SN1 pathways [002].
- Ketoses: Fructose-derived hemiacetals give mixtures of furanosyl and pyranosyl fluorides due to ring-chain tautomerism, making DAST less suitable for ketose fluoride synthesis compared to alternative reagents [001].
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