Synthesis of Arylated Nucleobases by Visible Light Photoredox

Article pubs.acs.org/joc

Synthesis of Arylated Nucleobases by Visible Light Photoredox Catalysis Andreas Graml, Indrajit Ghosh, and Burkhard König* Institut für Organische Chemie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany S Supporting Information *

ABSTRACT: Arylated nucleobases were synthesized by visible light photocatalysis using rhodamine 6G as photoredox catalyst and N,N-diisopropylethylamine as sacrificial electron donor. The high redox potential of this catalyst system is achieved by a consecutive photoinduced electron transfer process (conPET) and allows the room temperature conversion of brominated and chlorinated nucleobases or nucleobase precursors as starting materials. In contrast to many transition-metal-based syntheses, a direct C−H arylation of nitrogen-containing halogenated heterocycles is possible without protection of the N−H groups. The method provides a simple, metal-free alternative for the synthesis of biologically interesting arylated heterocycles under mild conditions.

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photocatalytic arylation of iodouracils.29 However, all of the reported synthetic methods require transition metal catalysts, auxiliary ligands, high temperatures, use of N-protected nucleobases, additional prefunctionalization of the starting materials, or the use of UV-light. Transition-metal-free visible light photoredox catalysis may provide an attractive alternative method for the functionalization of halogenated heteroarenes under very mild conditions. Not surprisingly, its potential in organic synthesis has been investigated intensively.30−33 Of particular interest are reactions using organic dye catalysts instead of commonly used Ru- or Ir-based photocatalysts.34,35 Although these catalysts are less expensive and less toxic compared to transition metal complexes, their use is limited to specific halogenated starting materials depending on the redox potentials.36 However, organic dyes, such as PDI or Rh-6G give access to halogenated heteroarenes as substrates for photoredox catalytic arylation reactions, as they exhibit very high redox potentials under visible light irradiation, due to a consecutive photoinduced electron transfer process (conPET).37−40 We report here a simple strategy for the functionalization of halogenated nucleobases or nucleobase precursors utilizing blue LEDs as visible light source, the organic dye rhodamine 6G (Rh-6G) as photocatalyst, and N,N-diisopropylethylamine (DIPEA) as a sacrificial electron donor. The photoredox arylation of uracil uses 6-chloro-2,4dimethoxypyrimidine as the starting material, as shown in Scheme 1. 6-Chloro-2,4-dimethoxypyrimidine (Ar−X) is activated by photoinduced electron transfer, yielding the

INTRODUCTION Nucleobases are well-known molecular building blocks in living organisms whose presence and function in the DNA or compounds such as ATP is important to sustain life. Their structure is based on pyrimidines and purines, which are common motifs in many natural products and biologically active compounds.1 Among others, certain derivatives of uracil have gained enormous attention as bactericides,2 insecticides,3 herbicides,4 or fungicides,5 in addition to their use as privileged structural units in drug discovery. 6 Many nucleobase-derived molecules have been investigated for potential use as cytostatic drugs in cancer treatment,7 as well as drugs against malaria8,9 or several viral diseases.10−13 A bioanalytical application is the use as DNA labels.14,15 The abundance of nucleobases in many interesting compounds triggered the development of efficient synthetic methods for their functionalization, especially functionalization of the uracil moiety at the C5 and C6 positions.16−19 Several methods for the synthesis of substituted nucleobases are reported, many based on transition-metal-catalyzed cross-coupling protocols.20,21 While C − C arylations are mostly realized by Suzuki−Miyaura couplings,22,23 alkenylations and alkynylations can be performed with Stille,24 Heck, or Sonogashira couplings.25 As a more direct synthesis, palladium-catalyzed C−H arylation strategies have emerged.26 In 2011, Hocek et al. reported a direct arylation of N-protected uracils with aryl halides,17 and recently Wnuk et al. developed a method for the arylation of 5-iodouracil nucleosides with arenes and heteroarenes.19 Furthermore, cross-dehydrogenative couplings without the need for halogenated starting materials are known.26,27 Moreover, in 2010 Rossi et al. reported a photochemical arylation of 2,4-methoxyprotected uracil,28 and most recently Zhang et al. described in 2015 a direct © 2017 American Chemical Society

Received: January 13, 2017 Published: March 1, 2017 3552

DOI: 10.1021/acs.joc.7b00088 J. Org. Chem. 2017, 82, 3552−3560

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The Journal of Organic Chemistry

Scheme 1. Photoredox Catalytic Synthetic Strategy for the Functionalization of Nucleobases and Related Structures (R = aryl, heteroaryl)

Table 1. Control Reactions

entry 1 2 3 4 5 a

reaction conditions 2a 2a 2a 2a 2a

(20 (20 (20 (20 (20

equiv), equiv), equiv), equiv), equiv),

DIPEA (1.5 equiv), Rh-6G (10 mol %), DMSO/H2O (12:1) DIPEA (1.5 equiv), Rh-6G (10 mol %), DMSO, no light no DIPEA, Rh-6G (10 mol %), DMSO DIPEA (1.5 equiv), no catalyst, DMSO DIPEA (1.5 equiv), Rh-6G (10 mol %), DMSO, air

yield [%]a 69b 0 trace 0 trace

Isolated yield. bReaction time 48 h.

corresponding radical anions (Ar−X•−) that fragments by releasing a chloride anion to generate the corresponding 2,4dimethoxypyrimidine radical that could be used for subsequent arylation reactions with suitable trapping reagents. Finally, hydrolysis of the functionalized 2,4-dimethoxypyrimidine provides uracil derivatives. The arylation of purine, pyrimidine, and other biologically relevant heterocycles starts from their respective commercially available bromides and chlorides. To achieve the one-electron reduction of the halogenated substrates initiating the substitution reaction, the previously reported high reduction power of excited stable radical anions of rhodamine 6G is required.

significantly lower product yields (see Supporting Information). Moreover, addition of H2O (DMSO/H2O, 12:1; v/v) to the reaction mixture enhanced the yield significantly to 46%. The yield was further improved to 69% (isolated yield, see Table 1) when the reaction mixture was irradiated for 48 h. Control reactions without the catalyst, without DIPEA, and without visible light irradiation did not lead to any significant product formation (Table 1, entries 2−4). Only traces of the coupling product were observed when the reaction was carried out in the presence of air (Table 1, entry 5). Having the optimized reaction conditions in hand (entry 1, Table 1), we then explored the scope of the photoredox catalytic arylation reaction of 1a with other pyrrole derivatives. These reactions gave the C−H arylated products in moderate to good yields (see Table 2). Notably, unprotected pyrrole could also be used with ease under this C−H arylation reaction protocol, and the reaction with N-benzylpyrrole as a trapping reagent gave exclusively the C−H arylated product 3e in 54% yield. In the case of N-benzylpyrrole, the 2 position of the pyrrole derivative was arylated chemoselectively. Other electron-rich arenes and heteroarenes could also be used as the coupling partners of the 2,4-dimethoxypyrimidine radical. Use of 1,3,5-trimethoxybenzene as a radical trapping reagent gave 3g in 27% yield. The relatively low yield is due to the competing hydrogen abstraction reactions of the 2,4dimethoxypyrimidine radical either from the solvent or from the radical cation of DIPEA (see below). The trapping with 3methylindole provides coupling product 3f in synthetically useful yield. 3-Methylindole was selectively functionalized at the 2 position. When 1,1-diphenylethylene was employed as

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RESULTS AND DISCUSSION Optimization of the photoredox reaction conditions was carried out by irradiation mixture of 6-chloro-2,4-dimethoxypyrimidine (1a), N-methylpyrrole (2a), rhodamine 6G (Rh6G), and N,N-diisopropylethylamine (DIPEA, sacrificial electron donor) with blue LEDs (455 ± 15 nm) under nitrogen atmosphere. With 10 mol % catalyst loading and 1.5 equiv of DIPEA in DMSO, a yield of 25% of the coupling product 3a was observed by gas chromatographic (GC) analysis after 24 h of irradiation. While the yield was similar in EtOH, it dropped drastically when the reaction was carried out in DMF (see Supporting Information). Excess amount of sacrificial electron donor (i.e., DIPEA) did not improve the reaction outcome. However, excess of trapping reagent (20 equiv) was important to suppress hydrogen abstraction from the solvent or the radical cation of DIPEA as a competing reaction pathway giving the dehalogenated starting material as the product. The use of only 5 or 10 equiv of 2 resulted in 3553


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The Journal of Organic Chemistry Table 2. Scope of Trapping Reagents (isolated yield)

a

The reaction was started with 10 mol % catalyst loading, and then 5 mol % catalyst was added after 20 h according to general procedure A. b15 equiv of 2. cYield determined by quantitative 1H NMR with 2,5-dimethylfuran as internal standard, dThe reaction was started with 10 mol % catalyst loading, and then 10 mol % was added in two batches (5 + 5 mol %) after 20 and 30 h. eCombined yield of saturated product 3h and unsaturated product 3h′ (3h:3h′ = 4.9:1). It is worth mentioning here that bleaching of the photoredox catalyst organic dye Rh-6G was observed. The bleaching rate differs depending on substrates and the trapping reagents. After complete decomposition of the photocatalyst (as could be observed by naked eyes), the conversion of the starting material to the respective C−H product stops. In cases of fast catalyst bleaching, the addition of photocatalyst increased the yields (for more details and for the spectroscopic investigations of the catalyst bleaching, see Supporting Information).

substituents present in the substrates.41 Substitution at another position of the uracil moiety could be performed by using commercially available 5-bromouracil (46% isolated yield), although a higher catalyst loading was needed in this case (see Supporting Information). When 6-chloropurine was employed under the photoredox protocol, the C−H arylated product 3b was obtained in moderate yield of 51%. We then explored this photoredox protocol for the generation of biologically important pyrimidine heteroaryl radicals from their respective bromides (see Table 4).42,43 The pyrimidine ring could be functionalized at the 5 position with 74% isolated yield (3j) and the 2 position with 33% yield (3k). When 6-bromo-2-methylbenzoxazole was used as a substrate, the coupling product 3l was obtained in 73% yield. Having realized that the redox power of the photoredox catalytic system could also exceed the reduction potentials of

trapping reagent, product 3h and 3h′ were obtained in an excellent combined yield of 82%. Subsequent to the coupling reactions, hydrolysis of the methoxy groups of the C−H arylated products gave substituted uracils in almost quantitative yields. Thus, after two steps, compounds 4a, 4d, and 4e were obtained in 66%, 57%, and 51% yields, respectively. Interestingly, the C−H arylated product 4a could also be obtained by using 6-chlorouracil directly as the substrate with 22% isolated yield (see Table 3). However, due to the low yield, the two-step synthesis including a simple hydrolysis step subsequent to the coupling reaction, is preferable for the synthesis of arylated uracils. Note that the rate of the C−H arylation reactions is not only determined by the reduction potential of the substrates but also by the carbon−halogen bond cleavage kinetics that depends strongly on the 3554


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The Journal of Organic Chemistry Table 3. Scope of Nucleobase Derivatives (isolated yield)

a The reaction was started with 10 mol % catalyst loading, and then 5 mol % catalyst was added after 20 h according to general procedure A. bThe reaction was started with 10 mol % catalyst loading, and then 10 mol % was added in two batches (5 + 5 mol %) after 20 and 30 h.

Table 4. Scope of Heteroaryl Bromides and Chlorides (isolated yield)

a

The reaction was started with 10 mol % catalyst loading, and then 5 mol % catalyst was added after 20 h according to general procedure A.

chlorinated heteroaromatic substrates, we then used heteroaryl chlorides as substrates for the C−H arylation reactions, giving access to biologically interesting heteroarenes.44−46 Coupling reactions with 2-chlorobenzimidazole, 2-chlorobenzothiazole, and 2-chlorobenzoxazole gave moderate to excellent yields of 3m (65%), 3n (96%), and 3o (55%), respectively.47

substrates, the nucleobase radical abstracts a hydrogen atom either from the solvent (in this case, DMSO) or from the radical cation of DIPEA, yielding the reduction product as observed in GC and GC-MS analysis of the crude reaction mixtures. Experimental results, spectroscopic investigations, cyclic voltammetric results, and literature reports support the proposed catalytic cycle. The results of the fluorescence titrations of Rh-6G with substrate 1a and DIPEA are shown in Figure 2. The fluorescence intensity of Rh-6G was not quenched upon titration with the substrate 1a. However, the fluorescence of Rh-6G was quenched dramatically upon addition of DIPEA, which is due to the formation of the radical anion of Rh-6G.38 The C−H arylation reaction did not proceed under green light (λEx = 530 ± 15 nm) irradiation of the reaction mixture. Note that the radical anion of rhodamine 6G is formed by irradiation with green light, but it cannot be excited again by using green light. At the same time, the radical anion of rhodamine 6G in the ground state is not capable of transferring an electron to the investigated substrates, which have exceptionally high reduction potentials. The measured reduction potentials for 1a, 1i, and 1b in

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MECHANISTIC PROPOSAL The proposed mechanism for the photoredox catalytic C−H arylation is depicted in Figure 1. Upon blue light irradiation, the excited Rh-6G takes an electron from DIPEA to generate the radical anion of rhodamine 6G and the radical cation of DIPEA.38 The radical anion, upon further photoexcitation, reduces the investigated substrates by an electron transfer, returning to its ground state and yielding the nucleobase radical by scission of the C−Br or C−Cl bond. Finally, the radical is either trapped by heteroarenes, double bonds, or substituted arenes present in the reaction media, yielding the C−H arylated products after oxidation and rearomatization. In a competing pathway, also reported for other photoredox catalytic C−H arylation reactions using aryl halides as 3555


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Figure 1. Proposed mechanism of the photocatalytic reductive cross-coupling reaction via a conPET type process.

Figure 2. Changes in the fluorescence spectra of Rh-6G (4.93 μM in DMSO) upon successive addition of 1a (i) and DIPEA (ii). The Stern− Volmer-quenching plot for the fluorescence titration with Rh-6G in the presence of DIPEA is shown in the inset of part ii.

DMSO are −2.32, −2.04, and −1.86 V vs SCE, respectively (see Supporting Information for the cyclic voltammograms). The reduction potential of Rh-6G, upon blue light irradiation, reaches or exceeds a value of ca. −2.4 V38 and thus could transfer an electron to the halogenated nucleobases or other halogenated heteroaromatic substrates investigated herein. Additionally, formation of the products 3h and 3h′ with 1,1-diphenylethylene (a radical scavenger that shows low reactivity toward nucleophiles or electrophiles)48 also supports the proposed radical mechanism. After addition of 1a• to 1,1diphenylethylene, product 3h′ is obtained by oxidation and deprotonation of the radical intermediate, while 3h is generated by hydrogen atom abstraction either from the radical cation of DIPEA or from the solvent (see Supporting Information). The role of water (present in 12:1 v/v) is not clear at the moment. However, knowing that solvents play a crucial role in determining the stability and reactivity of radical intermediates, including the radical anion of rhodamine 6G, generated in situ, and the photostability of the catalyst, we anticipate that water stabilizes the generated nucleobase

radical species and suppresses the degradation of the photocatalyst.

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CONCLUSION We report a mild metal-free photoredox catalytic method for the synthesis of arylated nucleobases from commercially available halogenated heterocycles. Under blue light irradiation, the strong reductive power of the excited radical anion of rhodamine 6G is used to reduce chloro- or bromosubstituted nucleobases and heterocycles to their respective radical anions. Upon elimination of a halide anion, the corresponding aryl radicals are generated. These are trapped by heteroarenes, 1,1-diphenylethylene, and electron-rich arenes present in the reaction mixture to afford the targeted functionalized nucleobases in good isolated yields. The reported photoredox catalytic protocol provides an alternative strategy to transition-metal-based cross-coupling protocols and C−H arylation protocols using halogenated nucleobases under UV-light irradiation. 3556


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for the remaining reaction time, one FPT cycle was performed subsequently. After the irradiation time, the reaction mixture was diluted with water and extracted with EtOAc (3 × 20 mL). The combined organic layers were dried over MgSO4, and the solvent was removed under reduced pressure. The crude product was purified by automated flash column chromatography (PE/EtOAc), and after evaporation of the solvent the product was obtained. 2,4-Dimethoxy-6-(1-methyl-1H-pyrrol-2-yl)pyrimidine (3a). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 48 h, automated column chromatography (PE/EtOAc, 5% EtOAc) gave product 3a as a slightly brown solid in 69% yield. 1 H NMR (400 MHz, CDCl3) δH [ppm] = 6.74 (d, J = 3.3 Hz, 2H), 6.55 (s, 1H), 6.16 (t, J = 3.2 Hz, 1H), 4.05 (s, 3H), 4.00 (s, 3H), 3.96 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 172.0 (Cq), 165.1 (Cq), 160.6 (Cq), 129.7 (Cq), 128.3 (+), 113.3 (+), 108.3 (+), 96.0 (+), 54.7 (+), 53.7 (+), 37.9 (+). HRMS (ESI) (m/z): [M + H]+ (C11H14N3O2) calcd: 220.1081, found 220.1087. 6-(1-Methyl-1H-pyrrol-2-yl)-7H-purine (3b). The product was obtained following general procedure A using 1h (30.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (10.1 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, the irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 80% EtOAc) gave product 3b as a white solid in 51% yield. 1H NMR (300 MHz, DMSO-d6) δH [ppm] = 13.39 (s, 1H), 8.78 (s, 1H), 8.50 (s, 1H), 7.75 (s, 1H), 7.11 (t, J = 2.2 Hz, 1H), 6.24 (dd, J = 3.9, 2.5 Hz, 1H), 4.14 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δC [ppm] = 151.9 (Cq), 151.3 (+), 148.4 (Cq), 143.1 (+), 129.6 (+), 127.8 (Cq), 126.6 (Cq), 118.9 (+), 108.4 (+), 38.0 (+). HRMS (ESI) (m/z): [M + H]+ (C10H10N5) calcd: 200.0931, found: 200.0934. 2,4-Dimethoxy-6-(1H-pyrrol-2-yl)pyrimidine (3c). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2c (278 μL, 4.0 mmol, 20 equiv) and DIPEA (25 μL, 0.3 mmol, 1.5 equiv). After 48 h automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3c as a white solid in 65% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 9.62 (s, 1H), 6.92 (td, J = 2.6, 1.4 Hz, 1H), 6.79 (ddd, J = 3.8, 2.5, 1.4 Hz, 1H), 6.51 (s, 1H), 6.30 (dt, J = 3.7, 2.6 Hz, 1H), 4.01 (s, 3H), 3.97 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 172.2 (Cq), 165.4 (Cq), 158.7 (Cq), 129.5 (Cq), 121.0 (+), 110.9 (+), 110.0 (+), 93.6 (+), 54.7 (+), 53.9 (+). HRMS (ESI) (m/z): [M + H]+ (C10H12N3O2) calcd: 206.0924, found: 206.0928. mp = 103−108 °C 2,4-Dimethoxy-6-(1-phenyl-1H-pyrrol-2-yl)pyrimidine (3d). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2d (572.8 mg, 4.0 mmol, 20 equiv) and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3d as an ochre brown solid in 58% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 7.42−7.31 (m, 3H), 7.28−7.22 (m, 2H), 6.97−6.92 (m, 2H), 6.35 (dd, J = 3.7, 2.8 Hz, 1H), 6.25 (s, 1H), 3.89 (s, 3H), 3.44 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 171.9 (Cq), 164.7 (Cq), 159.3 (Cq), 141.6 (Cq), 130.8 (Cq), 128.9 (+), 128.3 (+), 127.2 (+), 126.3 (+), 114.7 (+), 109.7 (+), 97.0 (+), 54.2 (+), 53.8 (+). HRMS (ESI) (m/z): [M + H]+ (C16H16N3O2) calcd: 282.1237, found: 282.1243. mp = 87−89 °C. 4-(1-Benzyl-1H-pyrrol-2-yl)-2,6-dimethoxypyrimidine (3e). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2e (611 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, the irradiation was continued.

EXPERIMENTAL SECTION

General Information. Starting materials and reagents were purchased from commercial suppliers and were used without further purification. Solvents were used as p.a. grade or dried and distilled according to known literature procedures.49 Industrial grade of solvents was used for automated flash column chromatography. All reactions with oxygen- or moisture-sensitive reagents were carried out in glassware that was dried before use by heating under vacuum. Dry nitrogen was used as an inert gas atmosphere. Liquids were added via syringe, needle, and septum technique unless stated otherwise. All NMR spectra were measured at room temperature (300 or 400 MHz for 1H, 75 or 101 MHz for 13C).50 All chemical shifts are reported in δ-scale as parts per million [ppm] (multiplicity, coupling constant J, number of protons) relative to the solvent residual peaks as the internal standard.51 Coupling constants J are given in hertz [Hz]. Abbreviations used for signal multiplicity: 1H NMR: b = broad, s = singlet, d = doublet, t = triplet, q = quartet, dd = doublet of doublets, dt = doublet of triplets, dq = doublet of quartets, and m = multiplet; 13C NMR: (+) = primary/tertiary, (−) = secondary, (Cq) = quaternary carbon). The mass spectrometric measurements were performed at the Central Analytical Laboratory of the University of Regensburg, using a TOF or Q-TOF mass analyzer. GC and GC-MS measurements were performed at the University of Regensburg. A 30 m × 0.25 mm/0.25 μM film capillary was used and helium served as carrier gas (flow rate of 1 mL/min). The injector temperature (split injection: 40:1 split) was 280 °C, detection temperature 300 °C (FID). GC measurements were made and investigated via integration of the signal obtained. The GC oven temperature program was adjusted as follows: initial temperature 40 °C was kept for 3 min, the temperature was increased at a rate of 15 °C/min over a period of 16 min until 280 °C was reached and kept for 5 min, the temperature was again increased at a rate of 25 °C/ min over a period of 48 s until the final temperature (300 °C) was reached and kept for 5 min. Benzophenone was chosen as internal standard. Analytical TLC was performed on silica-gel-coated alumina plates. Visualization was performed with UV light (254 or 366 nm). If necessary, vanillin was used for chemical staining. Purification by column chromatography was performed with silica gel 60 M (40−63 μm, 230−440 mesh). For irradiation, blue LEDs (λmax = 455 ± 15 nm, Imax = 1000 mA, 1.12 W) or green LEDs (λmax = 530 ± 15 nm, Imax = 1000 mA, 1.12 W) were used. Absorption and fluorescence spectra were performed with a quartz fluorescence cuvette at room temperature. CV measurements were performed with a threeelectrode potentiostat galvanostat using a glassy carbon working electrode, a platinum wire counter electrode, and a platinum wire reference electrode. Tetrabutylammonium tetrafluoroborate (TBATFB, 0.1 M) was used as supporting electrolyte. The potentials are given relative to Fc/Fc+ redox couple with ferrocene as internal standard. The measurements were carried out as follows: Prior to the measurement, a 0.1 M solution of TBATFB in DMSO was added to the measurement cell and the solution was degassed by argon purge for 5 min. All experiments were performed under argon atmosphere. After the baseline was recorded, the electroactive compound was added (0.01 M) and the solution was degassed again for 5 min. The cyclic voltammogram was recorded with one scan. Afterward, ferrocene (2.20 mg, 12 μmol) was added to the solution which was again degassed by argon purge for 5 min and the final measurement was performed. General Procedure A: Photoredox Catalytic Cross-Coupling. A 5 mL crimp vial was equipped with the aryl halide 1 (0.2 mmol, 1 equiv), rhodamine 6G (10 mg, 0.02 mmol, 10 mol %), the respective trapping reagent 2 (4.0 mmol, 20 equiv), DIPEA (52 μL, 0.3 mmol, 1.5 equiv), and a stirring bar. After addition of the solvent (1.5 mL), the vial was capped and degassed using the freeze−pump− thaw (FPT) technique three times. The reaction mixture was stirred and irradiated using blue LEDs (455 ± 15 nm) for 48 h. After 20 h, if necessary, 250 μL of a solution of the catalyst (c = 0.04 M) was added to the reaction mixture. This was performed with a Hamilton syringe under exclusion of oxygen. To ensure oxygen-free conditions 3557


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3H). 13C NMR (101 MHz, acetone) δC [ppm] = 172.9 (Cq), 166.0 (Cq), 165.6 (Cq), 150.2 (Cq), 143.1 (Cq), 141.3 (Cq), 130.5 (+), 129.6 (+), 129.6 (+), 129.4 (+), 128.7 (+), 128.7 (+), 127.2 (+), 126.8 (+), 126.8 (+), 101.7 (+), 54.6 (+), 54.0 (+). HRMS (ESI) (m/z): [M]+• (C20H17N2O2) calcd: 318.1363, found: 318.1347. 5-(1-Methyl-1H-pyrrol-2-yl)pyrimidine-2,4(1H,3H)-dione (3i): 52 The product was obtained following general procedure A using 1i (38.2 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h and after 30 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle after the addition of new catalyst, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 60% EtOAc) gave product 3i as a white, slightly brownish solid in 46% yield. 1H NMR (400 MHz, DMSO-d6) δH [ppm] = 11.22 (s, 1H), 11.03 (s, 1H), 7.37 (d, J = 3.9 Hz, 1H), 6.76 (t, J = 2.3 Hz, 1H), 5.96−5.93 (m, 2H), 3.43 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δC [ppm] = 163.2 (Cq), 151.2 (Cq), 141.3 (+), 125.6 (Cq), 123.2 (+), 109.5 (+), 106.6 (+), 105.9 (Cq), 34.2 (+). HRMS (ESI) (m/z): [M + H] (C9H10N3O2) calcd: 192.0773, found: 192.0773. 5-(1-Methyl-1H-pyrrol-2-yl)pyrimidine (3j). The product was obtained following general procedure A using 1j (31.8 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 25% EtOAc) gave product 3j as a reddish oil in 74% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 9.09 (s, 1H), 8.77 (s, 2H), 6.80 (dd, J = 2.7, 1.8 Hz, 1H), 6.35 (dd, J = 3.7, 1.8 Hz, 1H), 6.23 (dd, J = 3.7, 2.7 Hz, 1H), 3.69 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 156.5 (+), 155.4 (+), 127.6 (Cq), 127.1 (Cq), 126.0 (+), 110.9 (+), 108.9 (+), 35.3 (+). HRMS (ESI) (m/z): [M]+• (C9H9N3) calcd: 159.0791, found: 159.0788. 2-(1-Methyl-1H-pyrrol-2-yl)pyrimidine (3k). The product was obtained following general procedure A using 1k (31.8 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3k as a reddish oil in 33% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 8.64 (d, J = 4.8 Hz, 2H), 7.16 (dd, J = 3.9, 1.9 Hz, 1H), 6.96 (t, J = 4.8 Hz, 1H), 6.78 (t, J = 2.2 Hz, 1H), 6.20 (dd, J = 3.9, 2.5 Hz, 1H), 4.08 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 160.7 (Cq), 156.8 (+), 131.1 (Cq), 128.7 (+), 116.9 (+), 115.3 (+), 108.2 (+), 38.2 (+). HRMS (ESI) (m/z): [M]+• (C9H8N3) calcd: 158.0713, found: 158.0708. 2-Methyl-6-(1-methyl-1H-pyrrol-2-yl)benzo[d]oxazole (3l). The product was obtained following general procedure A using 1l (42.41 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3l as a white solid in 72% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 7.66 (d, J = 8.2 Hz, 1H), 7.49 (d, J = 1.0 Hz, 1H), 7.35 (dd, J = 8.2, 1.6 Hz, 1H), 6.74 (t, J = 2.2 Hz, 1H), 6.28− 6.21 (m, 2H), 3.67 (s, 3H), 2.65 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 164.2 (Cq), 151.2 (Cq), 140.5 (Cq), 134.2 (Cq), 130.2 (Cq), 125.3 (+), 123.9 (+), 119.0 (+), 110.3 (+), 109.2 (+), 108.0 (+), 35.1 (+), 14.6 (+). HRMS (ESI) (m/z): [M]+• (C13H12N2O) calcd: 212.0944, found: 212.0942. 2-(1-Methyl-1H-pyrrol-2-yl)-1H-benzo[d]imidazole (3m): 39 The product was obtained following general procedure A using 1m (30.5 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol

After 48 h, automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3e as a brown oil in 54% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 7.31−7.18 (m, 3H), 7.05−6.98 (m, 2H), 6.82 (m, 2H), 6.58 (s, 1H), 6.26 (dd, J = 3.8, 2.7 Hz, 1H), 5.84 (s, 2H), 3.94 (s, 3H), 3.77 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 172.0 (Cq), 165.1 (Cq), 160.5 (Cq), 139.3 (Cq), 129.7 (Cq), 128.6 (+), 127.8 (+), 127.2 (+), 126.4 (+), 113.7 (+), 109.2 (+), 96.5 (+), 54.6 (+), 53.8 (+), 52.5 (−). HRMS (ESI) (m/z): [M + H]+ (C17H18N3O2) calcd: 296.1394, found: 296.1398. 2-(2,6-Dimethoxypyrimidin-4-yl)-3-methyl-1H-indole (3f). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2f (393.5 mg, 3.0 mmol, 15 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h and after 30 h 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle after the addition of new catalyst, the irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3f as a white solid in 32% yield (determined by quantitative NMR analysis using 2,5-dimethylfuran as internal standard). 1H NMR (300 MHz, chloroform-d) δH [ppm] = 9.34 (s, 1H), 7.65 (dd, J = 8.0, 1.0 Hz, 1H), 7.40 (dt, J = 8.4, 1.0 Hz, 1H), 7.30−7.23 (m, 1H), 7.17−7.09 (m, 1H), 6.79 (s, 1H), 4.10 (s, 3H), 4.03 (s, 3H), 2.62 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 172.4 (Cq), 165.2 (Cq), 159.0 (Cq), 135.5 (Cq), 130.1 (Cq), 129.9 (Cq), 124.5 (+), 119.8 (+), 119.8(+), 114.2 (Cq), 111.5 (+), 97.5 (+), 55.0 (+), 54.1 (+), 11.0 (+). HRMS (ESI): [M + Na]+ (C15H15N3NaO2) calcd: 292.1056, found: 292.1057 2,4-Dimethoxy-6-(2,4,6-trimethoxyphenyl)pyrimidine (3g). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2g (504.6 mg, 3.0 mmol, 15 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, the irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 30% EtOAc) gave product 3g as a white solid in 27% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 6.38 (s, 1H), 6.18 (s, 2H), 3.98 (d, J = 1.3 Hz, 6H), 3.84 (s, 3H), 3.73 (s, 6H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 171.6 (Cq), 165.3 (Cq), 164.3 (Cq), 161.9 (Cq), 158.9 (Cq), 110.6 (Cq), 104.0 (+), 91.2 (+), 56.1 (+), 55.5 (+), 54.8 (+), 53.8 (+). HRMS (ESI) (m/z): [M]+• (C15H17N2O5) calcd: 305.1132, found: 305.1134. mp = 170−174 °C. 4-(2,2-Diphenylethyl)-2,6-dimethoxypyrimidine (3h). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2h (706 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 10% EtOAc) gave product 3h as a white solid in 68% yield. 1H NMR (400 MHz, acetone-d6) δH [ppm] = 7.39−7.31 (m, 4H), 7.28−7.21 (m, 4H), 7.17−7.10 (m, 2H), 6.24 (s, 1H), 4.74 (t, J = 8.0 Hz, 1H), 3.90 (s, 3H), 3.82 (s, 3H), 3.41 (d, J = 8.0 Hz, 2H). 13C NMR (101 MHz, acetone) δC [ppm] = 172.6 (Cq), 171.5 (Cq), 166.1 (Cq), 145.3 (Cq), 129.2 (Cq), 128.7 (+), 127.0 (+), 101.4 (+), 54.7 (+), 53.8 (+), 50.4 (+), 43.4 (−). HRMS (ESI) (m/z): [M]+• (C20H20N2O2) calcd: 320.1519 found: 320.1521. mp = 74−78 °C. 4-(2,2-Diphenylvinyl)-2,6-dimethoxypyrimidine (3h′). The product was obtained following general procedure A using 1a (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2h (706 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOH, 10% EtOAc) gave product 3h′ as a white solid in 14% yield. 1H NMR (400 MHz, acetone-d6) δH [ppm] = 7.43−7.36 (m, 7H), 7.30−7.24 (m, 1H), 7.22−7.19 (m, 2H), 6.95 (s, 1H), 5.98 (s, 1H), 3.80 (s, 3H), 3.57 (s, 3558


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The Journal of Organic Chemistry %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 15% EtOAc) gave product 3m as a white solid in 65% yield. 1H NMR (400 MHz, DMSO-d6) δH [ppm] = 12.45 (s, 1H), 7.62 (d, J = 7.0 Hz, 1H), 7.45 (d, J = 7.0 Hz, 1H), 7.15 (m, 2H), 6.99 (t, J = 2.2 Hz, 1H), 6.89 (dd, J = 3.8, 1.8 Hz, 1H), 6.17 (dd, J = 3.8, 2.6 Hz, 1H), 4.11 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δC [ppm] = 146.6 (+), 143.9 (Cq), 134.0 (Cq), 127.1 (+), 122.9(+), 121.9 (+), 121.2 (+), 118.3 (Cq), 111.3 (+), 110.5 (Cq), 107.8 (+), 36.6 (+). HRMS (ESI) (m/ z): [M + H]+ (C12H12N3) calcd: 198.1026, found: 198.1031. 2-(1-Methyl-1H-pyrrol-2-yl)benzo[d]thiazole (3n): 53 The product was obtained following general procedure A using 1n (33.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 5% EtOAc) gave product 3n as a brown oil in 96% yield. 1H NMR (400 MHz, CDCl3) δH [ppm] = 7.98 (dd, J = 8.2, 0.6 Hz, 1H), 7.84 (dd, J = 8.0, 0.6 Hz, 1H), 7.46 (ddd, J = 8.3, 7.2, 1.3 Hz, 1H), 7.33 (ddd, J = 8.3, 7.2, 1.2 Hz, 1H), 6.86 (dd, J = 3.9, 1.7 Hz, 1H), 6.83 (t, J = 2.2 Hz, 1H), 6.24 (dd, J = 3.9, 2.6 Hz, 1H), 4.17 (s, 3H). 13C NMR (101 MHz, CDCl3) δC [ppm] = 160.5 (Cq), 154.4 (Cq), 134.0 (Cq), 128.1 (+), 126.6 (+), 126.0 (+), 124.5 (+), 122.5 (+), 121.2 (+), 114.9 (+), 108.8 (+), 37.2 (+). HRMS (ESI) (m/z): [M]+• (C12H9N2S) calcd: 213.0481, found: 213.0480. 2-(1-Methyl-1H-pyrrol-2-yl)benzo[d]oxazole (3o): 53 The product was obtained following general procedure A using 1o (34.9 mg, 0.2 mmol, 1.0 equiv), Rh-6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 5% EtOAc) gave product 3o as a white solid in 55% yield. 1H NMR (300 MHz, CDCl3) δH [ppm] = 7.76−7.64 (m, 1H), 7.56−7.45 (m, 1H), 7.24 (s, 2H), 7.11 (dd, J = 3.9, 1.8 Hz, 1H), 6.87 (t, J = 2.2 Hz, 1H), 6.26 (dd, J = 4.0, 2.5 Hz, 1H), 4.15 (s, 3H). 13C NMR (75 MHz, CDCl3) δC [ppm] = 157.9 (Cq), 149.6 (Cq), 142.4 (Cq), 128.6 (+), 124.3 (+), 120.7 (Cq), 119.3 (+), 115.2 (+), 110.1 (+), 108.9 (+), 37.1 (+). HRMS (ESI) (m/z): [M + H]+ (C12H10N2O) calcd: 199.0866, found: 199.0867. mp = 85−90 °C. 6-(1-Methyl-1H-pyrrol-2-yl)pyrimidine-2,4(1H,3H)-dione (4a). The product was obtained following general procedure A using unprotected 6-chlorouracil 1a′ (29.3 mg, 0.2 mmol, 1.0 equiv), Rh6G (9.6 mg, 0.02 mmol, 10 mol %), 2a (355 μL, 4.0 mmol, 20 equiv), and DIPEA (52 μL, 0.3 mmol, 1.5 equiv). After 20 h, 250 μL of a solution of the catalyst (c = 0.04 M, 5 mol %) was added with a Hamilton syringe under exclusion of air. Subsequent to one FPT cycle, irradiation was continued. After 48 h, automated column chromatography (PE/EtOAc, 80% EtOAc) gave product 4a as a white solid in 22% yield. 1H NMR (300 MHz, DMSO-d6) δH [ppm] = 11.01 (s, 1H), 10.75 (s, 1H), 7.03 (dd, J = 2.6, 1.7 Hz, 1H), 6.67 (dd, J = 3.9, 1.8 Hz, 1H), 6.12 (dd, J = 3.9, 2.6 Hz, 1H), 5.56 (t, J = 1.8 Hz, 1H), 3.73 (s, 3H). 13C NMR (75 MHz, DMSO-d6) δC [ppm] = 164.1 (Cq), 151.7 (Cq), 144.6 (Cq), 129.0 (+), 124.2 (Cq), 113.4 (+), 108.0 (+), 96.6 (+),35.9 (+). HRMS (ESI) (m/z): [M + H]+ (C9H10N3O2) calcd: 192.0768, found: 192.0773. General Procedure B: Hydrolysis of Methoxy-Protected Uracils. The hydrolysis of 3 was performed according to the procedure described in the reference. A round-bottom flask was charged with 3, which was then dissolved in a mixture of MeOH/ HClconcd (25 mL, 1:1). The reaction mixture was heated to reflux and stirred for 24 h. Subsequently, a saturated solution of Na2CO3 (20 mL) was used to neutralize the acid, and water (10 mL) was added. After extraction with EtOAc (3 × 50 mL), the combined

organic layers were dried over MgSO4. The solvent was removed under reduced pressure, and evaporation of the remaining volatiles led to the crude product. Purification was performed by automated flash column chromatography (PE/EtOAc), and the hydrolyzed product was obtained as a white powder. 6-(1-Methyl-1H-pyrrol-2-yl)pyrimidine-2,4(1H,3H)-dione (4a). The product was prepared following general procedure B using 3a (53.0 mg, 0.24 mmol, 1.0 equiv). After purification by automated column chromatography (PE/EtOAc, 85% EtOAc), the product was obtained in 95% yield. This compound has also been synthesized via the photoredox catalytic coupling reaction. Due to the very similar work up and purification procedure, both methods provided this compound with similar purity. Therefore, see the photoredox catalytic coupling reaction in general procedure A for the characterization. 6-(1-Phenyl-1H-pyrrol-2-yl)pyrimidine-2,4(1H,3H)-dione (4d). The product was prepared following general procedure B using 3d (61.5 mg, 0.22 mmol, 1.0 equiv). After purification by automated column chromatography (PE/EtOAc, 80% EtOAc), the product was obtained as a white solid in 99% yield. 1H NMR (300 MHz, DMSOd6) δH [ppm] = 10.96 (s, 1H), 10.90 (s, 1H), 7.55−7.39 (m, 3H), 7.37−7.30 (m, 2H), 7.25 (dd, J = 2.8, 1.7 Hz, 1H), 6.96 (dd, J = 3.9, 1.7 Hz, 1H), 6.38 (dd, J = 3.9, 2.7 Hz, 1H), 4.68 (t, J = 1.8 Hz, 1H). 13 C NMR (75 MHz, DMSO-d6) δC [ppm] = 163.6 (Cq), 151.6 (Cq), 144.4 (Cq), 139.2 (Cq), 129.6 (+), 129.3 (+), 127.9 (+), 125.6 (+), 123.6 (Cq), 115.6 (+), 109.8 (+), 97.37 (+). HRMS (ESI) (m/z): [M + H]+ (C14H12N3O2) calcd: 254.0924, found: 254.0931. 6-(1-Benzyl-1H-pyrrol-2-yl)pyrimidine-2,4(1H,3H)-dione (4e). The product was prepared following general procedure B using 3e (60.6 mg, 0.21 mmol, 1.0 equiv). After purification by automated column chromatography (PE/EtOAc, 80% EtOAc), the product was obtained as a slightly brownish solid in 95% yield. 1H NMR (400 MHz, DMSO-d6) δH [ppm] = 10.94 (s, 1H), 10.80 (s, 1H), 7.35−7.28 (m, 2H), 7.28−7.21 (m, 1H), 7.17 (dd, J = 2.7, 1.8 Hz, 1H), 6.99−6.92 (m, 2H), 6.70 (dd, J = 3.9, 1.8 Hz, 1H), 6.23 (dd, J = 3.9, 2.7 Hz, 1H), 5.36−5.30 (m, 3H). 13C NMR (101 MHz, DMSO-d6) δC [ppm] = 163.8 (Cq), 151.5 (Cq), 144.5 (Cq), 138.2 (Cq), 128.6 (+), 127.4 (+), 126.2 (+), 124.2 (Cq), 114.1 (+), 108.6 (+), 96.8 (+), 51.0 (−). HRMS (ESI) (m/z): [M + H]+ (C15H14N3O2) calcd: 268.1081, found: 268.1090. mp = 219−223 °C.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b00088.

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Optimization of reaction condition and 1H and NMR spectra of all compounds (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: Burkhard.Kö[email protected]. ORCID

Burkhard König: 0000-0002-6131-4850 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by the Deutsche Forschungsgemeinschaft DFG, (GRK 1626; Chemical Photocatalysis). We thank Dr. Rudolf Vasold (University of Regensburg) for his assistance in GC-MS measurements and Ms. Regina Hoheisel (University of Regensburg) for her assistance in cyclic voltammetry measurements. 3559


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