Introducing aryl- and heteroaryl moieties into molecular scaffolds are often key steps in the syntheses of natural products, drugs, or functional materials. A variety of cross-coupling methods have been well established, mainly using transition metal mediated reactions between prefunctionalized substrates and arenes or C-H arylations with functionalization in only one coupling partner. Although highly developed, one drawback of the established sp2-sp2 arylations is the required transition metal catalyst, often in combination with specific ligands and additives. Therefore, photoredox mediated arylation methods have been developed as alternative over the past decade. We begin our survey with visible light photo-Meerwein arylation reactions, which allow C-H arylation of heteroarenes, enones, alkenes, and alkynes with organic dyes, such as eosin Y, as the photocatalyst. A good number of examples from different groups illustrate the broad application of the reaction in synthetic transformations. While initially only photo-Meerwein arylation-elimination processes were reported, the reaction was later extended to photo-Meerwein arylation-addition reactions giving access to the photoinduced three component synthesis of amides and esters from alkenes, aryl diazonium salts, nitriles or formamides, respectively. Other substrates with redox-active leaving groups have been explored in photocatalyzed arylation reactions, such as diaryliodonium and triarylsulfonium salts, and arylsulfonyl chlorides. We discus some examples with their scope and limitations. The scope of arylation reagents for photoredox reactions was extended to aryl halides. The challenge here is the extremely negative reduction potential of aryl halides in the initial electron transfer step compared to, e.g., aryl diazonium or diaryliodonium salts. In order to reach reduction potentials over -2.0 V vs SCE two consecutive photoinduced electron transfer steps were used. The intermediary formed colored radical anion of the organic dye perylenediimide is excited by a second photon allowing the one electron reduction of acceptor substituted aryl chlorides. The radical anion of the aryl halide fragments under the loss of a halide ion and the aryl radical undergoes C-H arylation with biologically important pyrrole derivatives or adds to a double bond. Rhodamine 6G as an organic photocatalyst allows an even higher degree of control of the reaction. The dye is photoreduced in the presence of an amine donor under irradiation with green light (e.g., 530 nm), yielding its radical anion, which is a mild reducing reagent. The hypsochromic shift of the absorption of the rhodamine 6G radical anion toward blue region of the visible light spectrum allows its selective excitation using blue light (e.g., 455 nm). The excited radical anion is highly reducing and able to activate even bromoanisole for C-H arylation reactions, although only in moderate yield. Photoredox catalytic C-H arylation reactions are valuable alternatives to metal catalyzed reactions. They have an excellent f...

Photosynthetic organisms exploit antenna chromophores to absorb light and transfer excitation energy to the reaction center where redox reactions occur.I nc ontrast, in visible-light chemical photoredoxc atalysis,asingle species (i.e., the photoredoxc atalyst) absorbs light and performs the redox chemistry.M imicking the energy flowo ft he biological model, we report at wo-center photoredoxc atalytic approach in which the tasks of light energy collection and electron transfer (i.e., redox reactions) are assigned to two different molecules.R u(bpy) 3 Cl 2 absorbs the visible light and transfers the energy to polycyclic aromatic hydrocarbons that enable the redox reactions.T his operationally simple sensitization-initiated electron transfer enables the use of arenes that do not absorb visible light, such as anthracene or pyrene,f or photoredox applications.Wedemonstrate the merits of this approach by the reductive activation of chemical bonds with high reduction potentials for carbon-carbon and carbon-heteroatom bond formations.Photosynthetic organisms transform light energy into chemical free energy through as eries of energy-transducing reactions.V isible light is harvested by antenna pigments, such as chlorophyll ba nd b-carotene,a nd transferred to the reaction center pigment, chlorophyll a, to drive photosynthetic reactions. [1][2] This strategy of using strongly absorbing antenna molecules for visible-light collection and weakly absorbing redox centers to drive chemical reactions enables the efficient conversion of light energy into redox energy for the simultaneous oxidation of water to molecular oxygen and the reduction of NADP + to NADPH. In contrast, visiblelight-mediated photoredox catalysis, [3][4][5][6][7] an emerging field in synthetic organic chemistry,u ses visible light to drive chemical reactions,but relies on the use of the same molecule (i.e., ap hotoredox catalyst) for both visible-light absorption and the conversion of the light energy into redox energy to initiate redox reactions.This excludes the application of many chromophores that have extremely high redox potentials,but do not absorb visible light (e.g., polycyclica romatic hydrocarbons for reduction reactions;c .f., sodium naphthalenide) in photoredox catalysis,and leads to astrong dependence on the inherent redox potentials of typical photoredox catalysts for the conversion of visible light into the maximum available redox energy.[8] Aside from the typically very long reaction times and relatively poor photochemical quantum yields,the restricted redox energy gain upon visible-light photoexcitation limits the overall performance of ap hotoredox catalyst with respect to the substrate scope.F urthermore,i na ccordance with the common notion that the more reductive ac atalyst, the less oxidative it is,s ynthetically demanding chemical modifications enhance the redox equivalence gain in one direction at the expense of the other (oxidative/reductive or vice versa).[9]Inspired by the natural photosynthetic systems,w e envisioned us...

Aryl phosphonates are functional groups frequently found in pharmaceutical and crop protection agents. For their synthesis via C–P bond formation typically transition-metal-catalyzed reactions are used. We report a visible-light photo-Arbuzov reaction as an efficient, mild, and metal-free alternative. Rhodamine 6G (Rh.6G) is used as the photocatalyst, generating aryl radicals under blue light. Coupling of the radicals with a wide range of trivalent phosphites gives aryl phosphonates in good to very good isolated yields. The mild reaction conditions allow the introduction of a phosphonate group into complex and sensitive pharmaceutically active molecules such as benzodiazepams and nicergoline by the activation of a carbon–halogen bond.

The direct transformationo fu biquitous, but chemically inert CÀHb onds into diversef unctional groups is an important strategy in organic synthesis that improves the atom economy and faclitates the preparation and modification of complex molecules.I nc ontrastt ot he wide applications of aryl phosphonates, their synthesis via direct CÀHb ondp hosphonylation is al ess exploreda rea. We report here ag eneral,m ild, and broadly applicable visible-light photoredox CÀHb ond phosphonylation method for electron-rich arenes and heteroarenes.T he photoredox catalytic protocol utilizes electron-rich arenes and biologically important heteroarenes as substrates, [Ru(bpz) 3 ][PF 6 ] 2 as photocatalyst, ammonium persulfate as oxidant, and trialkyl phosphites as the phosphorus source to provide aw ide range of aryl phosphonates at ambient temperature under very mild reaction conditions.

Sphingosine-1-phosphate (S1P) is a lysophospholipid that evokes a variety of biological responses via stimulation of a set of cognate G-protein coupled receptors (GPCRs): S1P1-S1P5. S1P and its receptors (S1PRs) play important roles in the immune, cardiovascular, and central nervous systems and have also been implicated in carcinogenesis. Recently, the S1P analogue Fingolimod (FTY720) has been approved for the treatment of patients with relapsing multiple sclerosis. This work presents the synthesis of various fluorinated structural analogues of FTY720, their in vitro and in vivo biological testing, and their development and application as [(18)F]radiotracers for the study of S1PR biodistribution and imaging in mice using small-animal positron emission tomography (PET).