Fluoroalkylsulfonyl chlorides, RfSO2Cl, in which Rf=CF3, C4F9, CF2H, CH2F, and CH2CF3, are used as a source of fluorinated radicals to add fluoroalkyl groups to electron‐deficient, unsaturated ...carbonyl compounds. Photochemical conditions, using Cu mediation, are used to produce the respective α‐chloro‐β‐fluoroalkylcarbonyl products in excellent yields through an atom transfer radical addition (ATRA) process. Facile nucleophilic replacement of the α‐chloro substituent is shown to lead to further diverse functionalization of the products.
Fluorinated radicals are generated under Cu catalysis from RfSO2Cl. They are used for atom transfer radical addition reactions with electron‐deficient alkenes such as α,β‐unsaturated ketones, amides, esters, carboxylic acids, sulfone, and phosphonate. ISET=inner single electron transfer.
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.
Nucleophilic fluorinated radicals: Photoredox‐catalyzed reductive difluoromethylation of electron‐deficient alkenes was achieved in one step under tin‐free, mild and neutral conditions (see scheme).
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.
Excess oxidative fluorination of 2,2′dipyridyl disulfides using a KF/Cl2/MeCN system led to the formation of thirteen new 2‐pyridylsulfur chlorotetrafluoride derivatives. These compounds were found to undergo further chlorine–fluorine exchange reactions with silver(I) fluoride enabling ready access to a series of substituted 2‐pyridylsulfur pentafluorides.
Using visible-light photoredox conditions, difluoromethylation and 1,1-difluoroalkylation of biphenyl isocyanides have allowed the synthesis of a series of 6-(difluoromethyl)- and ...6-(1,1-difluoroalkyl)phenanthridines via tandem addition/cyclization/oxidation processes. The reactions are carried out in wet dioxane at room temperature using fac-Ir(ppy)3 as catalyst to form a large variety of substituted phenanthridine products in good to excellent yield.
Fluorinated radicals were generated from RfSO2Cl by photoredox catalysis under mild conditions, where Rf = n-C4F9, CF3, CF2H, CH2F, CH2CF3, and CF2CO2Me. This method provided a general way to ...construct fluorinated 2-oxindoles from reaction with N-arylacrylamides via a proposed tandem radical cyclization process.
1,1,2,2‐Tetrafluoroethyl‐containing compounds are valuable structures due to their unique physicochemical properties, which have increasing potential application in drug discovery. However, synthetic ...methods for preparing such compounds are rare. Herein, we report the first use of 1,1,2,2‐tetrafluoroethanesulfonyl chloride to introduce the HCF2CF2 group into organic molecules via a three‐component, radical tetrafluoroethyl‐heteroarylation of alkenes with readily available quinoxalin‐2(1H)‐ones. This method provides a new and facile approach for late‐stage functionalization of potential biologically active molecules.
A convenient three‐component tetrafluoroethylation reaction of alkenes induced by visible light has been developed using 1,1,2,2‐tetrafluoroethylsulfonyl chloride and quinoxalin‐2(1H)‐ones. This method provides a facile approach to introduce the HCF2CF2 group into organic molecules under mild conditions, enabling the late‐stage modification of biologically active and drug molecules.
A visible light-mediated difluoromethylation of N-benzylacrylamides with HCF2SO2Cl as the HCF2 radical precursor is described. The reaction incorporates a tandem cyclization/dearomatization process ...to afford various difluoromethylated 2-azaspiro4.5deca-6,9-diene-3,8-diones bearing adjacent quaternary stereocenters under mild conditions in moderate to excellent yields.
A photoredox catalyzed aminodifluoromethylation of unactivated alkenes has been developed in which HCF2SO2Cl is used as the HCF2 radical source. Sulfonamides were active nucleophiles in the final ...step of a tandem addition/oxidation/cyclization process to form pyrrolidines, and esters were found to cyclize to form lactones. Thus, a variety of pyrrolidines and lactones were obtained in moderate to excellent yield. In order for the cyclization reactions to be efficient, a combination of a copper catalyst (Cu(dap)2Cl) and silver carbonate was crucial to suppressing a competing chloro, difluoroalkylation process.
Fluoroform, CHF3, a non-ozone-depleting, nontoxic, and inexpensive gas can be used as a difluorocarbene source in a process for the conversion of phenols and thiophenols to their difluoromethoxy ...and difluorothiomethoxy derivatives. The reactions are carried out at moderate temperatures and atmospheric pressure, using potassium hydroxide as base in a two-phase (water/dioxane or water/acetonitrile) process to provide moderate to good yields of the respective products.
1,1,2,2-Tetrafluoroethyl-containing molecules are of potential importance in drug discovery, but the efficient synthesis of such compounds is still relatively unexplored due to the lack of readily ...available reagents for the incorporation of the HCF2CF2 group. Herein, we introduce a new reagent, zinc 1,1,2,2-tetrafluoroethanesulfinate, which can be useful for the oxidative tetrafluoroethylation of arylboronic acids and heteroarenes as well as for a novel photoredox, three component hydro-tetrafluoroethylation of two alkenes of complementary reactivity.
