Visible-Light Photoredox-Catalyzed Three-Component Reaction of Carbazoles with Alkenes and S-(Difluoromethyl)sulfonium Salt: A Practical Approach to Access Difluoroalkyl-Functionalized Carbazoles.

A mild and elegant multicomponent protocol for construction of CF2H-containing carbazoles was accomplished by visible-light photoredox catalysis with formation of two new C-C bonds in a single step to deliver a wide variety of structurally diverse difluoroalkylated carbazoles in moderate to good yields, featuring mild reaction conditions, synthetic simplicity, broad substrates, and good functional group tolerance.

Visible-light photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)sulfonium salt.

A facile and highly efficient visible-light photoredox-catalyzed protocol for aryldifluoromethylation of acrylamides was developed using S-(difluoromethyl)sulfonium salt as the difluoromethyl source. With this method, pharmaceutically interesting CF2H-containing oxindoles were readily accessed from N-arylacrylamides, and this method featured mild reaction conditions, a broad scope of substrates, good tolerance of functional groups, and good to excellent yields. Control experiments revealed that this protocol proceeded through a difluoromethylation/cyclization cascade process.

Facile Entry to Pharmaceutically Important 3-Difluoromethyl-quinoxalin-2-ones Enabled by Visible-Light-Driven Difluoromethylation of Quinoxalin-2-ones.

CF2H moiety has a significant potential utility in drug design and discovery, and the incorporation of CF2H into biologically active molecules represents an important and efficient strategy for seeking lead compounds and drug candidates. On the other hand, quinoxalin-2-one is of great interest to pharmaceutical chemists as a common skeleton frequently occurring in plenty of natural products and bioactive compounds. Herein, we reported a practical and efficient protocol for the synthesis of 3-CF2H-quinoxalin-2-ones. Thus, in the presence of 3 mol% of photocatalyst and S-(difluoromethyl)sulfonium salt as difluoromethyl radical sources, a wide range of quinoxalin-2-ones readily underwent a visible-light redox-catalyzed difluoromethylation reaction, to deliver structurally diverse 3-difluoromethyl-quinoxalin-2-ones. We believe that this would facilitate increasing chances and possibilities for seeking potential lead compounds and drug candidates and further boost the development of fluorine-containing pharmaceuticals.

Difluoromethyl Radical Triggered Tandem Reaction of N-Allyl Amides to Difluoromethylated ß-Amino Alcohols by Photoredox Catalysis.

An elegant tandem reaction process for transferring N-allyl amide into CF2H-ß-amino alcohol is described. This approach proceeded smoothly under visible light irradiation in the presence of a 3 mol % Ir complex, exhibiting a broad substrate scope and functional group tolerance, and a variety of CF2H-ß-amino alcohols were readily accessed in good to excellent yields under mild conditions. The reliable mechanistic studies revealed that sequential difluoromethyl radical addition/carbocation trap/rearrangement is involved.