How to Bypass α-Fluoride Elimination: Bromine-Transfer Capture and Oxidative Coupling of α,α-Difluorobenzylic Anions
How to Bypass α-Fluoride Elimination: Bromine-Transfer Capture and Oxidative Coupling of α,α-Difluorobenzylic Anions
Introduction
Deprotonation is an important approach to carbon–hydrogen bond functionalization. After a base removes a proton from a carbon atom, a carbanion or organometallic species can be formed, which can subsequently react with an electrophile to construct a new carbon–carbon or carbon–heteroatom bond.
Whether such a method proceeds successfully depends on whether the resulting anionic intermediate can enter the subsequent reaction before decomposing. This issue is particularly important for α,α-difluoromethylarenes.
α,α-Difluoromethylarenes can be represented as:
Ar–CF₂H
where Ar represents an aryl or heteroaryl group. A base can promote deprotonation of the difluoromethyl group, but the resulting α,α-difluorobenzylic anionic species readily undergoes α-fluoride elimination, leading to decomposition of the fluorinated structure. Consequently, the conventional procedure of “first generating the carbanion and then adding the electrophile” is difficult to apply directly to this class of substrates.
In 2025, Hooker and Bandar reported a base-promoted oxidative coupling method in which 2-bromothiophene-derived reagents capture short-lived α,α-difluorobenzylic anions to form electrophilic Ar–CF₂Br intermediates in situ. Subsequent substitution by oxygen- or sulfur-based nucleophiles affords α,α-difluorobenzylic ethers or thioethers.[1]
The significance of this study lies not only in establishing a synthetic method for fluorinated compounds, but also in demonstrating a strategy for handling unstable intermediates: rather than requiring the intermediate to persist for an extended period, simultaneous capture and sequential conversion allow it to enter the desired reaction before substantial decomposition occurs.
1 Why Directly Use Ar–CF₂H to Construct Carbon–Oxygen and Carbon–Sulfur Bonds
α,α-Difluorobenzylic ethers and α,α-difluorobenzylic thioethers contain the following structures, respectively:
Ar–CF₂–OR
Ar–CF₂–SR
where R represents an alkyl, aryl, or other organic group. The inductive and stereoelectronic effects of the two fluorine atoms influence the molecular electron distribution, preferred conformation, lipophilicity, and stability. These structures have therefore attracted attention in medicinal chemistry, agrochemical research, and functional materials research.[1]
Traditional routes often begin with preconstructed esters, thioesters, or other carbonyl-containing precursors, followed by deoxofluorination or related steps to form the difluoromethylene unit. Some thioether routes also involve thiocarbonyl intermediates. Such methods require the carbon–oxygen or carbon–sulfur linkage to be established in advance and employ highly reactive fluorinating reagents. The number of synthetic steps and functional-group compatibility are therefore influenced by the specific substrate structure.[1]
From a route-design perspective, directly coupling Ar–CF₂H with an alcohol, phenol, or thiophenol can reduce reliance on preformed fluorinated intermediates:
Ar–CF₂H + H–Nu → Ar–CF₂–Nu
Here, Nu represents a nucleophilic group. H–Nu refers to a neutral compound such as an alcohol, phenol, or thiophenol. These compounds form nucleophiles upon base-promoted deprotonation and are therefore also described as pronucleophiles.
Although the reaction appears simply to replace the hydrogen atom of the difluoromethyl group with an oxy or thio group, it must in fact address two problems simultaneously: decomposition of the anionic intermediate and a mismatch in reaction polarity.
2 Two Chemical Obstacles to Direct Deprotonation
2.1 α,α-Difluorobenzylic anions readily undergo α-fluoride elimination
Under basic conditions, Ar–CF₂H can undergo deprotonation:
Ar–CF₂H —base-promoted deprotonation→ reactive Ar–CF₂ anionic species
The original paper notes that the actual form of Ar–CF₂⁻ remains unclear. It may be an organopotassium species or a hydrogen-bonded complex formed with the conjugate acid of the base. Ar–CF₂⁻ therefore mainly represents a reactive state in which negative charge is concentrated at the difluorobenzylic carbon; it does not imply that a free carbanion has been isolated or directly characterized.[1]
This anion belongs to the class of α-fluorinated carbanions. Because the negatively charged carbon center is directly bonded to fluorine atoms, it can readily enter a decomposition pathway through α-fluoride elimination. The key issue is therefore not whether the proton can be removed, but whether the anion formed after deprotonation can be captured before substantial decomposition occurs.[1]
A previous study used lithium diisopropylamide to deprotonate 3-(difluoromethyl)pyridine at −100 °C, followed by electrophilic trapping of the resulting species. However, that method showed a pronounced dependence on substrate structure and low-temperature conditions.[2] Another study used a combination of a strong Brønsted base and a weak Lewis acid to convert Ar–CF₂H into an isolable boron–nitrogen heterocyclic anionic adduct, which was subsequently reacted with electrophiles.[3]
2.2 A carbanion cannot directly form a bond with another nucleophile
Alcohols, phenols, and thiophenols form alkoxides, phenoxides, and thiophenolates, respectively, under basic conditions:
ROH + Base → RO⁻
ArOH + Base → ArO⁻
ArSH + Base → ArS⁻
These anions and Ar–CF₂⁻ are all nucleophilic. Two nucleophilic species generally cannot directly form the desired carbon–oxygen or carbon–sulfur bond.
The reaction design therefore cannot stop at “generating two anions.” The difluorobenzylic carbon must also be converted from a nucleophilic center into an electrophilic center capable of accepting nucleophilic attack.
3 How Halogen Transfer Achieves Intermediate Capture and Polarity Inversion
This method combines deprotonation, bromine transfer, and nucleophilic substitution within the same reaction process:
Ar–CF₂H
→ reactive Ar–CF₂ anionic species
→ Ar–CF₂Br
→ Ar–CF₂–Nu
The three steps perform different functions.
3.1 Deprotonation generates a reactive anion
The base removes a proton from Ar–CF₂H, producing a low concentration of the α,α-difluorobenzylic anionic species. Because this intermediate is prone to decomposition, it is not suitable for prolonged accumulation in the reaction mixture.
3.2 2-Bromothiophene-derived reagents transfer electrophilic bromine
The newly generated anion acquires bromine from a 2-bromothiophene-derived reagent and is converted into Ar–CF₂Br:
Reactive Ar–CF₂ anionic species + bromine-transfer reagent → Ar–CF₂Br
This process does not imply that free Br⁺ is present in solution. Rather, the 2-bromothiophene-derived reagent provides the nucleophilic carbon center with the equivalent of electrophilic bromine.
Formation of Ar–CF₂Br serves two functions:
① It rapidly converts the anion that is prone to α-fluoride elimination;
② It converts the nucleophilic difluorobenzylic carbon into an electrophilic carbon center.
Halogen transfer therefore functions both as an intermediate-capture step and as a polarity-inversion step.
3.3 Nucleophilic substitution forms carbon–oxygen or carbon–sulfur bonds
After formation, Ar–CF₂Br can undergo substitution with an alkoxide, phenoxide, or thiophenolate present in the system. The net transformation can be represented as:
Ar–CF₂Br + Nu⁻ → Ar–CF₂–Nu + Br⁻
Ar–CF₂Br does not need to be isolated, but instead undergoes further conversion in situ to the target product. The overall process therefore constitutes a sequence of “anion generation–halogenative capture–nucleophilic substitution.”[1]
This design builds on the research group’s previously developed base-promoted halogen-transfer reactions. Related studies have shown that 2-halothiophene-derived reagents can participate in halogen transfer and sequential substitution involving aryl or benzylic carbon–hydrogen bonds under basic conditions.[4]
4 Why the Three Steps Must Be Connected Within the Same Reaction System
The key to understanding this method is not the reactivity of any individual step in isolation, but the matching of the rates of the three steps.
4.1 The anion is captured promptly after it is generated
Conventional stepwise procedures generally use a strong base to generate an organometallic species before adding the electrophile. For a relatively unstable Ar–CF₂ anion, this procedure may allow α-fluoride elimination to occur before the electrophile is introduced.
In the halogen-transfer system, the base and bromine-transfer reagent are present simultaneously. Once the anion is formed, it can immediately enter the bromine-transfer process, reducing its accumulation in the reaction mixture.
4.2 Ar–CF₂Br continues to be consumed after it is formed
Halogen transfer is not the endpoint of the reaction. Once formed, Ar–CF₂Br is further consumed by oxygen- or sulfur-based nucleophiles in the system. This process both forms the desired carbon–heteroatom bond and reduces the opportunity for the halogenated intermediate to participate in other reactions.
Control experiments in the original paper showed that when the system contained Ar–CF₂H, a base, and a 2-bromothiophene-derived reagent but lacked a pronucleophile, the mass balance of Ar–CF₂H-derived species still decreased. This finding indicates that halogen transfer and nucleophilic substitution must be connected sequentially; addition of the halogen-transfer reagent alone is insufficient to sustain the desired transformation.[1]
4.3 The method changes the reaction pathway rather than the intrinsic stability of the anion
Halogen transfer does not demonstrate that the Ar–CF₂ anion itself becomes stable. Instead, the method relies on kinetic capture: the anion remains prone to decomposition, but after its formation it is rapidly converted into Ar–CF₂Br and then proceeds to the target product.
The central logic of this study can therefore be summarized as follows:
Control the generation and consumption of the unstable intermediate so that it is rapidly captured and further converted into the target product before substantial decomposition occurs.
5 How Substrate Acidity Affects the Choice of Base and Bromine-Transfer Reagent
Based on the difficulty of deprotonating Ar–CF₂H, the original study established two principal sets of reaction conditions.[1]
Substrate characteristics | Base | Solvent and additive | Bromine-transfer reagent |
Relatively acidic difluoromethylarenes or difluoromethyl heteroarenes | Potassium tert-butoxide (KOtBu) | N,N-Dimethylformamide (DMF) | 2-Bromothiophene or a related reagent |
Relatively less acidic difluoromethylarenes | Potassium bis(trimethylsilyl)amide (KHMDS) | Tetrahydrofuran (THF) and 18-crown-6 | 2-Bromo-3-phenylbenzo[b]thiophene |
5.1 Relatively acidic substrates
Electron-deficient heteroarenes such as difluoromethylpyridines are more readily deprotonated. For this class of substrates, potassium tert-butoxide and 2-bromothiophene form an effective reaction combination.
Potassium tert-butoxide not only promotes deprotonation of Ar–CF₂H, but also converts phenols, alcohols, or thiophenols into the corresponding nucleophilic anions.
5.2 Relatively less acidic substrates
4-(Difluoromethyl)biphenyl, (difluoromethyl)benzene, and electron-rich difluoromethylarenes are more difficult to deprotonate. When potassium tert-butoxide is used, 2-bromothiophene may undergo undesired consumption before the target anion is formed.
The researchers therefore used KHMDS together with 18-crown-6 to modulate potassium-ion coordination and selected 2-bromo-3-phenylbenzo[b]thiophene, which is more stable under strongly basic conditions, as the bromine-transfer reagent. This combination enabled less readily deprotonated substrates to participate in the reaction.
These results show that the reaction conditions must simultaneously account for two factors:
① Whether the base can promote Ar–CF₂H deprotonation at an appropriate rate;
② Whether the bromine-transfer reagent can maintain a sufficient effective concentration before the anion is formed.
The identity of the base, substrate acidity, potassium-ion coordination state, reaction medium, and stability of the bromine-transfer reagent must be appropriately matched. KHMDS conditions do not give the same outcome for every class of substrate. For example, the paper notes that for a relatively acidic model substrate, the yield under KHMDS conditions was lower than that obtained with potassium tert-butoxide.[1]
6 What Types of α,α-Difluorobenzylic Derivatives Can Be Synthesized by This Method
6.1 Scope of difluoromethylarenes and difluoromethyl heteroarenes
The study examined various α,α-difluoromethylarenes ranging from electron-deficient to electron-rich substrates, including:
① Nitrogen-containing heteroarenes bearing a difluoromethyl group;
② Substrates containing an aryl chloride or aryl bromide;
③ Arenes bearing a trifluoromethyl substituent;
④ Substrates containing an ether, acetal, amide, or nitrile group;
⑤ (Difluoromethyl)benzene and electron-rich difluoromethylarenes.
Aryl halides, ethers, acetals, amides, and nitriles could be retained under the corresponding conditions. Substrates containing aryl chlorides or aryl bromides underwent functionalization mainly at the Ar–CF₂H group, without displacement of the aryl halide becoming the predominant reaction pathway.[1]
6.2 Oxygen-based nucleophiles
The reaction is applicable to various phenols, including those bearing electron-withdrawing or electron-donating substituents. Phenols with a certain degree of ortho steric hindrance can also participate in the reaction, and the paper presents an example involving coupling of a sterically hindered phenol derived from vitamin E.
In addition to phenols, certain primary and secondary alcohols can form the corresponding α,α-difluorobenzylic ethers. An unsaturated alcohol substrate containing an alkene and allylic carbon–hydrogen bonds retained its double bond, indicating that no pronounced alkene addition or competing allylic reaction was observed in this example.
6.3 Sulfur- and nitrogen-based nucleophiles
Thiophenols can participate in the reaction to generate α,α-difluorobenzylic thioethers. Under the conditions examined in the study, alkyl thiols did not undergo effective conversion.
Amines can undergo coupling, but the resulting α,α-difluoroamine products are susceptible to hydrolysis and could not be isolated in a stable form. Therefore, the product classes currently supported by sufficient experimental evidence remain primarily α,α-difluorobenzylic ethers and aryl thioethers.[1]
6.4 Reaction-site selectivity is controlled by carbon–hydrogen bond acidity
Some substrates contain Ar–CF₂H together with a conventional aryl methyl group or a secondary benzylic carbon–hydrogen bond. The reaction occurs predominantly at the difluoromethyl position, while the conventional benzylic carbon–hydrogen bond remains intact.
This selectivity differs from that of radical halogenation, in which the reaction site is determined according to bond-dissociation energies. Because this method begins with base-promoted deprotonation, the reaction site is governed mainly by carbon–hydrogen bond acidity and the ability to form the corresponding anionic species.[1]
7 What Experiments Support the Involvement of an Ar–CF₂Br Intermediate
The original paper used reaction monitoring and control experiments to support a “deprotonation–bromine transfer–nucleophilic substitution” sequence.[1]
7.1 A small amount of Ar–CF₂Br was detected during the reaction
In a time-course experiment using the model reaction, the researchers detected a low concentration of a putative Ar–CF₂Br intermediate. This species did not accumulate to a high level, while the target α,α-difluorobenzylic ether gradually formed.
This observation is consistent with a process in which Ar–CF₂Br undergoes further nucleophilic substitution after its formation.
7.2 Independently prepared Ar–CF₂Br can form the target product
The researchers independently prepared the corresponding Ar–CF₂Br compound and then reacted it with 4-methoxyphenol and potassium tert-butoxide. The intermediate was converted into the target difluorobenzylic ether, demonstrating that Ar–CF₂Br is chemically competent to connect the halogen-transfer and nucleophilic-substitution steps.
7.3 The substrate is rapidly lost when only the base is used
When the model Ar–CF₂H substrate was mixed with potassium tert-butoxide, the researchers observed a rapid loss of mass balance in several solvents. This result indicates decomposition of the difluorobenzylic anionic species and is consistent with its known tendency to undergo α-fluoride elimination; however, the specific decomposition products were not directly identified in this control experiment.
7.4 The mass balance cannot be effectively maintained in the absence of a pronucleophile
When the reaction system contained the substrate, base, and a 2-bromothiophene-derived reagent but no phenol or alcohol, a substantial loss of Ar–CF₂H-derived species was still observed. This result indicates that effective conversion depends on the coordinated operation of deprotonation, bromine transfer, and nucleophilic substitution.
These experiments support the involvement of Ar–CF₂Br as a reaction intermediate, but they do not establish the rates of every microscopic step or clarify the precise structure of the reactive Ar–CF₂ anionic species.
8 Practical Value, Limitations, and Reaction-Design Implications of the Method
8.1 Modular combinations facilitate the preparation of fluorinated building blocks
By independently varying the difluoromethylarene and the oxygen- or sulfur-based nucleophile, this method can provide different Ar–CF₂–OR or Ar–CF₂–SR structures. Compared with routes that first prepare an ester or thioester and then perform deoxofluorination, this modular strategy facilitates the synthesis of series of derivatives based on the difluorobenzylic framework.[1]
8.2 The bromine-transfer reagent can be recovered and regenerated
For relatively less acidic substrates, the reaction uses a stoichiometric amount of 2-bromo-3-phenylbenzo[b]thiophene. In an etherification reaction conducted on an 11.5 mmol scale, the researchers used approximately 5 g of this reagent. After the reaction, the debrominated product was isolated and re-brominated with N-bromosuccinimide (NBS), giving an overall bromine-transfer reagent recovery of 88%.[1]
This result demonstrates that the reagent framework can be recycled. However, practical scale-up must still consider reagent preparation, stoichiometric consumption, recovery and purification, re-bromination, and waste treatment.
8.3 The current method remains limited by strong bases and substrate structure
The method currently has the following limitations:
① Relatively less acidic substrates require KHMDS, 18-crown-6, and a specialized bromine-transfer reagent;
② Strong bases may affect substrates containing acidic protons, readily enolizable carbonyl groups, or other base-sensitive functional groups;
③ Alkyl thiols have not yet shown effective reactivity;
④ Amine-coupling products are susceptible to hydrolysis;
⑤ The isolated yields of some substrates are affected by unreacted starting material, by-products, and purification losses;
⑥ The precise structure of the reactive anion and certain microscopic mechanistic details remain to be further investigated.[1]
8.4 What reaction-design principles does the study provide?
Four broadly applicable design principles can be extracted from this study.
First, identify the principal decomposition pathway of the intermediate.
For an Ar–CF₂ anion, the key competing reaction is α-fluoride elimination. The capture step must occur before substantial decomposition.
Second, control the generation and consumption of the highly reactive intermediate.
The reaction does not seek to accumulate a large amount of the carbanion. Instead, it allows the intermediate to enter the bromine-transfer process immediately after it is generated.
Third, allow the capture step to simultaneously alter the reaction polarity of the intermediate.
The Ar–CF₂ anion is nucleophilic and cannot directly couple with another nucleophile. Bromine transfer converts it into electrophilic Ar–CF₂Br, establishing an appropriate polarity combination for the subsequent nucleophilic substitution.
Fourth, provide a sequential conversion step for the captured product.
After formation, Ar–CF₂Br continues to be consumed by the nucleophile, allowing deprotonation, capture, and bond formation to work together to drive the overall reaction.
These principles may also assist in analyzing other carbanion systems that readily undergo elimination, ring opening, polymerization, or rearrangement. Whether a similar method can be applied must be evaluated in relation to the rate of anion generation, the stability of the capture reagent, the rate of the capture reaction, and the ability of the captured intermediate to undergo subsequent conversion.[1,4]
9 Classification and Research Applications of Representative Chemicals Related to Halogen-Transfer Capture and Oxidative Coupling of α,α-Difluorobenzylic Anions
Note: The following products include α,α-difluoromethylarene substrates, halogen-transfer reagents, strong bases, coordination additives, reaction solvents, oxygen- and sulfur-based pronucleophiles, and reagent-regeneration components. They are mainly used in research on halogen transfer, intermediate capture, base-promoted deprotonation, nucleophilic substitution, and reaction-condition comparisons. Some phenol and alcohol products are structural extensions selected according to the substrate types reported in the paper and do not indicate that each product has been individually validated under the specific reaction conditions reported by Hooker and Bandar.
Table 1 Difluoromethyl Substrates, Halogen-Transfer Reagents, Bases, and Reaction Media
Classification | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Less acidic difluoromethylarene substrate | 455-31-2 | (Difluoromethyl)benzene | ≥98% | Used as a model substrate for less acidic difluoromethylarenes and in studies of strong-base-promoted deprotonation, competition from α-fluoride elimination, and halogen-transfer conditions. | |
Core halogen-transfer reagent | 1003-09-4 | 2-Bromothiophene | ≥98% | Used to capture short-lived difluorobenzylic anions, generate difluorobenzylic bromide intermediates in situ, and investigate base-promoted oxidative coupling. | |
Structural reference for benzothiophene-based halogen-transfer reagents | 5394-13-8 | 2-Bromobenzo[b]thiophene | ≥96% | Used as a structural reference for benzothiophene-based bromine-transfer reagents and in studies comparing substituent effects and preparing related derivatives. | |
Reaction base for more readily deprotonated substrates | 865-47-4 | Potassium tert-butoxide | ≥98% | Used in difluoromethyl-group deprotonation, activation of phenols or alcohols, and sequential bromine-transfer–nucleophilic-substitution studies. | |
Strong base for less acidic substrates | 40949-94-8 | Potassium bis(trimethylsilyl)amide solution | 1.0 M in methyl tert-butyl ether | Used in strong-base-promoted deprotonation of less acidic difluoromethylarenes, generation of reactive anionic species, and halogen-transfer coupling studies. | |
Base-condition control | 865-48-5 | Sodium tert-butoxide | ≥98% | Used to compare base strength, metal-cation effects, substrate-deprotonation efficiency, and halogen-transfer conditions. | |
Potassium-ion coordination additive | 17455-13-9 | 18-Crown-6 | Ion-pair chromatography grade, ≥99% (GC) | Used to complex potassium ions, regulate ion-pairing states, and facilitate the deprotonation and halogen transfer of less acidic difluoromethylarenes. | |
Ether reaction solvent | 109-99-9 | T1491789 | Tetrahydrofuran (THF) | Anhydrous, ≥99.9%, unstabilized, H₂O ≤30 ppm | Used in deprotonation, halogen transfer, and sequential nucleophilic substitution reactions involving potassium bis(trimethylsilyl)amide and 18-crown-6. |
Polar aprotic reaction solvent | 68-12-2 | N,N-Dimethylformamide (DMF) | Anhydrous, ≥99.8% | Used in difluoromethyl activation, phenoxide formation, and oxidative coupling studies involving potassium tert-butoxide and 2-bromothiophene. | |
Highly polar aprotic solvent | 7226-23-5 | N,N′-Dimethylpropyleneurea (DMPU) | ≥99% | Used to regulate ion pairing in highly polar media and to compare conditions for difluoromethyl deprotonation and halogen-transfer reactions. |
Table 2 Phenol and Alcohol Pronucleophiles
Classification | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Electron-rich phenol model pronucleophile | 150-76-5 | 4-Methoxyphenol (MEHQ) | AR, ≥99% | Used in electron-rich phenol model reactions, coupling-condition optimization, phenoxide nucleophilic substitution, and difluorobenzylic ether construction studies. | |
Basic phenol pronucleophile | 108-95-2 | Phenol | UltraBio™, molecular biology grade, ≥99.5% | Used in basic phenol nucleophilic substitution, phenoxide formation, substituent-effect comparisons, and carbon–oxygen bond construction studies. | |
Electron-withdrawing phenol pronucleophile | 100-02-7 | 4-Nitrophenol | Analytical standard, ≥99.5% (HPLC) | Used to investigate the acidity, nucleophilicity, reaction rate, and halogen-transfer coupling applicability of phenols bearing electron-withdrawing substituents. | |
Complex sterically hindered phenol pronucleophile | 59-02-9 | D-α-Tocopherol | Moligand™, ≥97% (GC) | Used in late-stage functionalization of complex sterically hindered phenols, evaluation of steric-hindrance tolerance, and difluorobenzylic ether construction studies. | |
Primary alcohol pronucleophile | 100-51-6 | Benzyl alcohol | Anhydrous, ≥99.8% | Used to investigate the scope of primary alcohol nucleophiles, alkoxide substitution, difluorobenzylic ether synthesis, and carbon–oxygen bond formation. | |
Secondary alcohol pronucleophile | 108-93-0 | Cyclohexanol | AR, ≥98.5% (GC) | Used in studies of secondary-alcohol nucleophilic substitution, steric effects, alkoxide reactivity, and difluorobenzylic ether synthesis. |
Table 3 Chemicals for the Preparation and Regeneration of Halogen-Transfer Reagents and for Reaction-Condition Controls
Classification | CAS No. | Aladdin Catalog No. | Name | Specification or Purity | Product Features and Applications |
Precursor for halogen-transfer reagent synthesis | 70-11-1 | 2-Bromoacetophenone | ≥98% | Used in precursor synthesis for benzothiophene-based halogen-transfer reagents, development of cyclization routes, and preparation of customized reagents. | |
Brominating reagent for halogen-transfer reagent regeneration | 128-08-5 | N-Bromosuccinimide (NBS) | AR, ≥99% | Used to re-brominate debrominated benzothiophene frameworks and in studies of halogen-transfer reagent recovery, regeneration, and bromination conditions. | |
Iodinated halogen-transfer reagent control | 3437-95-4 | 2-Iodothiophene | ≥97%, stabilized with copper | Used as an iodinated halogen-transfer reagent control and in studies of deiodination tendencies under strongly basic conditions and halogen-transfer selectivity. | |
Extended control for related halogen-transfer systems | 3141-27-3 | 2,5-Dibromothiophene | ≥96% | Used to compare the reactivity, regioselectivity, reagent consumption, and side reactions of polyhalogenated thiophenes in related base-promoted halogen-transfer systems. | |
Conventional brominating reagent control | 558-13-4 | Carbon tetrabromide | ≥99% | Used as a conventional electrophilic brominating reagent control and in comparative studies of carbanion-capture capability and halogen-transfer mechanisms. |
Note: The products listed above are representative Aladdin products related to organic synthesis and reaction research. Additional product specifications, grades, and Certificates of Analysis can be retrieved from the Aladdin website using the product name, CAS number, or catalog number.
References
[1] Hooker L V, Bandar J S. Capturing Unstable Carbanionic Intermediates via Halogen Transfer: Base-Promoted Oxidative Coupling Reactions of α,α-Difluoromethylarenes. Angewandte Chemie International Edition, 2025, 64(21): e202502894. DOI: 10.1002/anie.202502894.
[2] Santos L, Panossian A, Donnard M, Vors J P, Pazenok S, Bernier D, Leroux F R. Deprotonative Functionalization of the Difluoromethyl Group. Organic Letters, 2020, 22(21): 8741–8745. DOI: 10.1021/acs.orglett.0c03380.
[3] Geri J B, Wade Wolfe M M, Szymczak N K. The Difluoromethyl Group as a Masked Nucleophile: A Lewis Acid/Base Approach. Journal of the American Chemical Society, 2018, 140(30): 9404–9408. DOI: 10.1021/jacs.8b06093.
[4] Bone K I, Puleo T R, Delost M D, Shimizu Y, Bandar J S. Direct Benzylic C–H Etherification Enabled by Base-Promoted Halogen Transfer. Angewandte Chemie International Edition, 2024, 63(39): e202408750. DOI: 10.1002/anie.202408750.
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