Efficient synthesis of p-bis-(chlorodifluoromethyl)benzene

Selective, high yield partial fluorination of p-bis-(trichloromethyl)benzene to p-bis-(chlorodifluoromethyl)benzene has been accomplished by warming a slurry of the p-bis-(trichloromethyl)benzene in anhydrous HF which also contains a small quantity of inert solvent, such as 1,2-dichloroethane.     

Absolute rate constants for some hydrogen atom abstraction reactions by a primary fluoroalkyl radical in water

A combination of laser flash photolysis and competitive kinetic methods have been used to measure the absolute bimolecular rate constants for hydrogen atom abstraction in water from a variety of organic substrates including alcohols, ethers, and carboxylic acids by the perfluoroalkyl radical, *CF(2)CF(2)OCF(2)CF(2)SO(3)(-) Na(+). Comparison, where possible, of these rate constants with those previously measured for analogous reactions in the non-polar organic solvent, 1,3-bis(trifluoromethyl)benzene (J. Am. Chem. Soc, 1999, 121, 7335) show that the alcohols react 2-5 times more rapidly in the water solvent and that the ethers react at the same rate in both solvents. A transition state for hydrogen abstraction that is more reminiscent of an "intimate ion pair" than a "solvent separated ion pair" is invoked to explain these modest solvent effects.     

Synthesis of 2-pentafluorosulfanylnaphthalene

A three step synthesis of 2-pentafluorosulfanylnaphthalene is reported. Initial addition of SF₅Cl to benzobarralene was followed by elimination to form 2-pentafluorosulfanylbenzobarralene. Heating of this compound with 3,6-bis-(2-pyridyl)-1,2,4,5-tetrazine led to elimination of the ethylene bridge via a sequence of cycloadditions and retro-cycloadditions to form the title compound.     

Synthesis and novel reactivity of halomethyldimethylsulfonium salts

Iodomethyl-, chloromethyl-, and fluoromethyldimethylsulfonium salts, 4b-d, have been synthesized and are observed to be highly reactive molecules that exhibit extraordinary diversity with respect to the nature of their reactivity, undergoing facile direct substitution (S(N)2) reactions, but also being highly susceptible to electron-transfer reactions. Cyclic voltametry experiments indicated that the iodomethyldimethylsulfonium compound, 4b, is a potent electron acceptor, even surpassing the reactivity of perfluoro-n-alkyl iodides in that capacity. The iodo- and chloromethyldimethylsulfonium salts, 4b,c, as well as the analogous iodomethyltrimethylammonium salt, 3a, are shown to be reactive SET acceptors.     

A new synthesis of pentafluorosulfanylbenzene

[reaction: see text] A new and convenient three-step synthesis of pentafluorosulfanylbenzene from 1,4-cyclohexadiene with an overall yield of >70% is reported along with a number of derivatization reactions.     

Reactions of trimethylsilyl fluorosulfonyldifluoroacetate with purine and pyrimidine nucleosides

Difluorocarbene, generated from trimethylsilyl fluorosulfonyldifluoroacetate (TFDA), reacts with the uridine and adenosine substrates preferentially at the enolizable amide moiety of the uracil ring and the 6-amino group of the purine ring. 2′,3′-Di-O-benzoyl-3′-deoxy-3′-methyleneuridine reacts with TFDA to produce 4-O-difluoromethyl product derived from an insertion of difluorocarbene into the 4-hydroxyl group of the enolizable uracil ring. Reaction of the difluorocarbene with the adenosine substrates having the unprotected 6-amino group in the purine ring produced the 6-N-difluoromethyl derivative, while reaction with 6-N-benzoyl protected adenosine analogues gave the difluoromethyl ether product derived from the insertion of difluorocarbene into the enol form of the 6-benzamido group. Treatment of the 6-N-phthaloyl protected adenosine analogues with TFDA resulted in the unexpected one-pot conversion of the imidazole ring of the purine into the corresponding N-difluoromethylthiourea derivatives. Treatment of the suitably protected pyrimidine and purine nucleosides bearing an exomethylene group at carbons 2′, 3′ or 4′ of the sugar rings with TFDA afforded the corresponding spirodifluorocyclopropyl analogues but in low yields.     

Novel ring-cleaving reaction of 4-nitro-1,1,2,2,9,9,10,10-octafluoro[2.2]paracyclophane with nucleophiles

When 4-nitro-AF4 is treated with nucleophiles such as alkoxides and cyanide, a novel ring opening, cyclophane destroying reaction is observed whereby, via an S_NAr mechanism, the nucleophile attacks the bridgehead aryl carbon vicinal to the nitro group with subsequent aryl-CF₂ bond cleavage.     

Synthesis and Characterization of 2‐Pyridylsulfur Pentafluorides

Current approaches to prepare SF₅‐substituted heterocycles during the synthesis of targeted heterocyclic compounds require the use of SF₅‐functionalized aryl or alkyne reagents or SF₅Cl as a source of the SF₅ functional group. Herein we report that excess oxidative fluorination of 2,2′‐dipyridyl disulfide with a KF/Cl₂/MeCN system leads to the formation of thirteen new 2‐pyridylsulfur chlorotetrafluorides (2‐SF₄Cl‐pyridines). These molecules are found to undergo further chlorine–fluorine exchange reactions by treatment with silver(I) fluoride enabling ready access to a series of ten new substituted 2‐pyridylsulfur pentafluorides (2‐SF₅‐pyridines). This is the first preparatively simple and readily scalable example of the transformation of an existing heterocyclic sulfur functionality to prepare SF₅‐substituted heterocycles.     

Direct Photoredox‐Catalyzed Reductive Difluoromethylation of Electron‐Deficient Alkenes

Photoredox‐catalyzed reductive difluoromethylation of electron‐deficient alkenes was achieved in one step under tin‐free, mild and neutral conditions. This protocol affords a facile method to introduce RCF₂ (R=H, Ph, Me, and CH₂N₃) groups at sites β to electron‐withdrawing groups. It was found that TTMS (tris(trimethylsilyl)silane) served nicely as both the H‐atom donor and the electron donor in the catalytic cycle. Experimental and DFT computational results provided evidence that RCF₂ (R=H, Ph, Me) radicals are nucleophilic in nature.