ChemInform Abstract: Aminodifluorosulfinium Salts: Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling.

Abstract

The title salts are more stable and more easily handled than DAST and Deoxo-Fluor and can be prepared in a safer and more cost-effective manner. In combination with DBU, NEt3·3HF, or NEt3·2HF they allow convenient formation of alkyl fluorides from alcohols, gem-difluorides from carbonyl compounds, and α-fluorothioethers from sulfoxides. -(L'HEUREUX, A.; BEAULIEU, F.; BENNETT, C.; BILL, D. R.; CLAYTON, S.; LAFLAMME, F.; MIRMEHRABI, M.; TADAYON, S.; TOVELL, D.; COUTURIER*, M.; J. Org.

Development of a Scalable Synthetic Route to BMS-986251, Part 2: Synthesis of the Tricyclic Core and the API

“…The safety concerns associated with DAST, as well as the slow reaction, prompted us to examine alternative deoxofluorinating agents. While Deoxo-Fluor 24 and XtalFluor-M 25 did not lead to the perfluoroalkylated compound 21 (entries 2 and 3, Table 2), XtalFluor-E 25 provided ∼10% conversion in the presence of Et 3 N and Et 3 N•3HF (entry 4). Encouraged by this result, we sought to explore other additives in conjunction with XtalFluor-E to bolster the reaction conversion.…”

“…Encouraged by this result, we sought to explore other additives in conjunction with XtalFluor-E to bolster the reaction conversion. Gratifyingly, the use of DBU (3 equiv, entry 5) led to ∼67% conversion, 25 and after fine-tuning, the reaction was improved to 98% conversion using 1.2 equiv of DBU (entry 6). Lowering the stoichiometry of DBU further to 0.5 equiv led to a drop in conversion (entry 7), and, finally, the reaction did not proceed at all in the absence of DBU (entry 8).…”

The Synthesis and Glycoside Formation of Polyfluorinated Carbohydrates

“…Stable, crystalline derivatives such as diethylaminodifluorosulfinium tetrafluoroborate (XtalFluor-E, pronounced 'crystalfluor'), essentially the product of reaction from DAST with BF3, have been introduced by the Couturier team at OmegaChem. [129][130][131] Because its reactive fluoride is now sequestered by BF3, a promoter such as Et3N•3HF or 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) is required for the reaction.…”

“…XtalFluor-E is used, there is no free fluoride to scavenge the proton released in the formation of B, essentially leading to the formation of the strong acid HBF4, leading to C. 130 Interestingly, this intermediate C was suggested not to be a good electrophile for reaction with fluoride, leading to side reactions, including reaction with another equivalent of alcohol to form symmetrical ethers, and loss of diethyl amine, ultimately leading to the formation of symmetrical sulfites (not shown). 130 This can be mitigated by adding an external fluoride source, such as Et3N•3HF, or also by adding a base such as DBU, preventing the formation of C. Hence, formation of intermediate D with release of another fluoride is promoted, which can then undergo reaction with the released fluoride to give E. 130,140 Scheme 1. A possible mechanism for DAST/DeoxoFluor and XtalFluor-mediated deoxyfluorination of alcohols.…”

Straightforward and Relatively Safe Process for the Fluoride Exchange of Trivalent and Tetravalent Group 13 and 14 Phthalocyanines

“…XtalFluor-E has successfully been used as a fluorinating reagent for alcohols and carbonyls, such as aldehydes and ketones. 52 Three polar aprotic solvents were explored; DMF, Nmethylpyrrolidine (NMP), and DMSO. Despite polar aprotic solvents being the most common for this type of reaction, research shows that the H-bonding network of a protic solvent can be manipulated through the use of additives to further optimize the production of halogenated MPcs.…”