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. 2023 Sep 7;88(19):13934–13945. doi: 10.1021/acs.joc.3c01517

Catalytic Photoredox C–H Arylation of 4-Oxo-4H-pyrido[1,2-a]pyrimidine-3-diazonium Tetrafluoroborates and Related Heteroaryl Diazonium Salts

Kris Antolinc 1, Helena Brodnik 1, Uroš Grošelj 1, Bogdan Štefane 1, Nejc Petek 1,*, Jurij Svete 1,*
PMCID: PMC10563132  PMID: 37676813

Abstract

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Irradiation of mixtures of title diazonium salts and heteroarenes with green light (510 nm) in the presence of eosin Y disodium salt (EY-Na2) as a photocatalyst furnished the corresponding arylation products in 8–63% yields. The proposed photocatalytic cycle is analogous to that proposed previously for closely related photoredox C–H arylations with aryl diazonium salts as aryl radical sources. This method has a broad substrate scope and represents a metal-free alternative for the synthesis of 3-heteroaryl-substituted 4H-quinolizin-4-ones and azino- and azolo-fused pyrimidones with a bridgehead nitrogen atom.

1. Introduction

Fused heterocycles with bridgehead nitrogen atoms are important scaffolds commonly used as building blocks for applications in medicinal chemistry, bioorganic chemistry, catalysis, and materials science.1 In this context, quinolizines2 and pyrido[1,2-a]pyrimidines3 are of particular interest due to their biological activity. The significance of these fused systems is supported by the literature data,4 which show that 4-oxo-3-phenyl-4H-pyrido[1,2-a]pyrimidine is a substructure of more than 850 known biologically active compounds. They are associated with 21 different bioindicators, such as cardiovascular- (416),5,6 antitumor- (374),7,8 nervous system- (321),9,10 anti-inflammatory (306),11,12 and anti-infective agents (284).13,14 As many of these heterocyclic systems are fluorescent, they are also suitable for fluorescent sensing and labeling.15 Some examples of biologically active 3-aryl-4H-quinolizine-4-one16,17 and 3-aryl-4H-pyrido[1,2-a]pyrimidin-4-one derivatives, including the anti-allergic drug pemirolast18 are depicted in Figure 1.

Figure 1.

Figure 1

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Some examples of biologically active 3-aryl-4H-quinolizin-4-one and 3-aryl-4H-pyrido[1,2-a]pyrimidin-4-one derivatives.

Known methods for the synthesis of 3-heteroaryl-substituted 4-oxo-4H-quinolizine and 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives (Figure 2) comprise cyclative condensation of 2-enamino- or 2-formamidino-substituted pyridine derivatives with α-[(hetero)aryl]acetyl chlorides (Figure 2, method A),2,3,6 transition metal-catalyzed direct C–H arylation of 3-unsubstituted quinolizinones and pyrido[1,2-a]pyrimidones with haloarenes (Figure 2, method B),2,3,7,19 and halogenation of the same starting compounds at position 3, followed by Suzuki–Miyaura arylation (Figure 2, method C).2,3,20 Despite their simplicity, the drawbacks of these synthetic approaches are the limited availability of α-(heteroaryl)acetyl chlorides (Figure 2, method A) and the use of transition-metal catalysts in the final synthetic step (Figure 2, methods B and C). Therefore, more sustainable and environmentally friendly methods that use readily available reagents and avoid the use of transition-metal catalysts are highly welcome. Recently, Kshirsagar and Bhawale reported visible-light-assisted direct C–H arylation of pyrido[1,2-a]pyrimidin-4-ones and thiazolo[3,2-a]pyrimidin-5-ones with aryl diazonium tetrafluoroborates under mild reaction conditions (Figure 2, method D).21 A complementary way to access title compounds is organocatalyzed photoredox-catalyzed arylation of 4-oxo-4H-quinolizine-3- and 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-diazonium salts, accessible in three steps from alkyl 2-acylamino-3-(dimethylamino)propenoates (Figure 2, method E).22

Figure 2.

Figure 2

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Synthesis of 3-(hetero)aryl-substituted 4-oxo-4H-quinolizines and 4-oxo-4H-pyrido[1,2-a]pyrimidines.

Aryldiazonium salts are useful and versatile reagents with widespread applications in organic synthesis including arylation reactions.23 In organic photoredox catalysis,24 aryldiazonium salts are widely used for the arylation of arenes, alkenes, and alkynes.25 However, the use of aryldiazonium salts in known photoredox transformations is mostly limited to derivatives of benzenediazonium salts, while the use of their bicyclic and heterocyclic analogues remains poorly represented.24,25

In this context, we reported the synthesis of quinolizinone-diazonium tetrafluoroborates26 and azino-27,28 and azolo-fused pyrimidone-diazonium tetrafluoroborates.29 Under thermal conditions, these diazonium salts underwent various ring-transformation reactions to afford 1H-1,2,3-triazole,27−29 indolizine,26,30 pyrazole,31 and pyridine derivatives.30,32 Substitution of the diazonium group by the azido group30 and reduction to 3-unsubstituted analogues with isopropanol26,28,29 have also been carried out. In extension, we reasoned that these heteroaryldiazonium tetrafluoroborates could also serve as a source of heteroaryl radical intermediates. Accordingly, they could be used as valuable precursors in photocatalytic C–H arylation reactions to obtain 3-heteroaryl-substituted quinolizinones and fused pyrimidinones in an environmentally friendly and sustainable manner (cf. Figure 2, method E). Consequently, we performed a study on the arylation of title diazonium salts with a series of heteroarenes under photocatalytic conditions. Herein, we present the results of the study, which confirmed the applicability of title diazonium tetrafluoroborates in catalytic photoredox C–H arylation reactions.

2. Results and Discussion

2.1. Synthesis and Arylation of Diazonium Salts

Title diazonium salts, 1-cyano-4-oxo-4H-quinolizine-3-diazonium tetrafluoroborate (1a),26 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-diazonium tetrafluoroborate (1b),27 and 5-oxo-5H-thiazolo[3,2-a]pyrimidin-6-diazonium tetrafluoroborate (1c)29 were selected as model substrates for photocatalytic arylation reactions. Compounds 1a–c were prepared in three steps from methyl 2-benzyloxycarbonylamino-3-(dimethylamino)propenoate and (2-pyridyl)acetonitrile, 2-aminopyridine, and 2-aminothiazole, respectively, following the literature procedures.26,27,29 Inspired by closely related C–H arylation of heteroarenes with aryl diazonium salts reported by König and co-workers,33 we have chosen their optimized reaction conditions as the starting point for our study. Eosin Y disodium salt (EY-Na2) was suitable as a photocatalyst as the absorption maxima of diazonium salts 1a–c (below 425 nm) did not interfere with the absorption maximum of EY-Na2 at 520 nm (Figures S9–S12).34 Irradiation of a mixture of diazonium salt 1b (1 equiv), thiophene (2b, 10 equiv), and EY-Na2 (1 mol %) with green light (λ = 510 nm) in degassed anhydrous DMSO under nitrogen at 20 °C for 4 h, followed by extraction workup gave the arylation product 3b as a 4:1 mixture of two regioisomers in a 15% isolated yield (Scheme 1, conditions A). Replacing DMSO33 with aqueous acetonitrile (acetonitrile/water, 9:1),23−25,35 increased the yield to 53% as an 81:19 mixture of two isomers. In this case, extraction workup was not necessary and the product was isolated by flash chromatography (FC) only. Neutral alumina proved to be an optimal stationary phase because the catalyst and polar components remained absorbed, allowing for easy isolation of the pure, less polar product 3b. The reaction of 1b with excess furan (2a) under these conditions afforded the arylation product 3a as a single isomer in a 63% isolated yield (Scheme 1, conditions B).

Scheme 1. Title Diazonium Tetrafluoroborates 1a–c and the Preliminary Visible-Light-Mediated C–H Arylation of 1b with Thiophene (2b) in DMSO and with Furan (2a) and Thiophene (2b) in Aqueous Acetonitrile.

Scheme 1

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Based on preliminary results, we decided to use the reaction of diazonium tetrafluoroborate 1b with furan (2a) as a model reaction for the subsequent optimization study. The results of the optimization study are shown in Table 1. Irradiation of a mixture of diazonium salt 1b (1 equiv), furan (2a) (10 equiv), and EY-Na2 (1 mol %) with green light (λ = 510 nm) in a 9:1 mixture of acetonitrile and water at 20 °C for 4 h gave the arylation product 3a in a 77% NMR yield (Table 1, entry 1). The yields of 3a were lower when the content of water was either gradually increased to a 1:1 ratio (Table 1, entries 2 and 3) or gradually decreased to 19:1 (Table 1, entries 4 and 5). No product 3a was observed in anhydrous acetonitrile and other organic solvents, such as ethyl acetate, methanol, THF, and toluene (Table 1, entry 6). This is consistent with the insolubility of the diazonium salts in anhydrous organic solvents. Higher catalyst loading did not improve the yield (Table 1, entries 7 and 8) while decreasing the amount of catalyst to 0.5 mol % resulted in a slight decrease in yield to 64% (Table 1, entry 9). Shortening the wavelength from 510 nm (green light) to 450 nm (blue light) had a negligible effect on the yield (69%, Table 1, entry 10). Without light and in the presence of EY-Na2, the conversion was slowed down to give 3a in a 41% yield after 20 h (Table 1, entry 11), while without light and photocatalyst, the yield was 31% after 24 h (Table 1, entry 12). When the reaction under standard conditions (MeCN/H2O = 9:1, λ = 510 nm, 1 mol % EY-Na2) was performed in a non-degassed solvent, it showed a slight decrease in NMR yield to 68% after 4 h (Table 1, entry 13). In contrast, without light and catalyst, the NMR yield in non-degassed solvent was only 3% after 4 h (Table 1, entry 14), while lowering the reaction temperature to 4 °C stopped the reaction (Table 1, entry 15). Replacement of EY-Na2 with [Ru(bpy)3](PF6)2, rose bengal disodium salt (RB-Na2), rhodamine B, and 9-mesityl-10-methylacridinium perchlorate (Mes-Acr-MeClO4) as photocatalysts resulted in a decrease of the yield (Table 1, entries 16–19). These results clearly indicated that the initial reaction conditions (MeCN/H2O = 9:1, λ = 510 nm, 1 mol % EY-Na2, degassed solvent, nitrogen atmosphere) were optimal (Table 1, entry 1).

Table 1. Optimization of the Reaction Conditions Using 1b + 2a → 3a as Model Transformationa.

2.1.

entry MeCN/H2O time (h) T (°C) λ (nm) photocatalyst (mol %) yield (%)b
1 9:1 4 20 510 EY-Na2 (1) 77
2 7:1 4 20 510 EY-Na2 (1) 55
3 1:1 4 20 510 EY-Na2 (1) 50
4 12:1 4 20 510 EY-Na2 (1) 25
5 19:1 4 20 510 EY-Na2 (1) 21
6 100:0c 4 20 510 EY-Na2 (1) 0c
7 9:1 4 20 510 EY-Na2 (2.5) 70
8 9:1 4 20 510 EY-Na2 (5) 60
9 9:1 4 20 510 EY-Na2 (0.5) 64
10 9:1 4 20 450 EY-Na2 (1) 69
11 9:1 20 20 d EY-Na2 (1) 41
12 9:1 24 20 d no catalyst 31
13 9:1 4 20 510 EY-Na2 (1) 68e
14 9:1 4 20 d no catalyst 3e
15 9:1 20 4 d no catalyst 1e
16 9:1 4 20 450 [Ru(bpy)3](PF6)2 (1) 49
17 9:1 4 20 510 RB-Na2 (1)f 45
18 9:1 4 20 510 rhodamine B (1) 49
19 9:1 4 20 450 Mes-Acr-MeClO4 (1)g 66
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a

Unless otherwise stated, the following standard reaction conditions were used: diazonium salt 1b (0.2 mmol), furan 2a (2 mmol), MeCN/H2O (9:1, 2 mL), EY-Na2 (1 mol %), λ = 510 nm, T = 20 °C, and t = 4 h.

b

NMR yield; determined using 1,3,5-trimethoxybenzene as an internal standard.

c

No product 3a formation was observed also in MeOH, THF, EtOAc, and toluene.

d

No light.

e

In non-degassed solvent under an air atmosphere.

f

Rose bengal disodium salt.

g

9-Mesityl-10-methylacridinium perchlorate.

With the optimized reaction conditions in hand, the substrate scope was examined. The results are shown in Scheme 2. First, diazonium tetrafluoroborate 1b was treated with heteroarenes 2a–f, ferrocene (2g), and benzene (2h) under optimized reaction conditions to give the corresponding arylation products 3a–h in 13–63% isolated yields (Scheme 2). Reactions of 1b with furan (2a), 2-methylfuran (2d), ferrocene (2g), and benzene (2h) gave the corresponding 3-(hetero)aryl-4-oxo-4H-pyrido[1,2-a]pyrimidines 3a, 3d, 3g, and 3h as single products in 13–63% isolated yields. The reaction of 1b with thiophene (2b) gave the arylation product 3b/3′b as an 81:19 mixture of the major 2-thienyl- (3b) and the minor 3-thienyl-isomer 3′b in 53% isolated yield. Similarly, treatment of 1b with 1-tert-butoxycarbonyl-1H-pyrrole (2f) gave the arylation product 3f/3′f as a 93:7 mixture of the respective pyrrol-2-yl- (3f) and pyrrol-3-yl-substituted isomer 3′f in 47% isolated yield. Reactions of 1b with benzofuran (2c) and benzothiophene (2e) gave the corresponding arylation products 3c and 3e as mixtures of at least five regioisomers. The substrate scope was further explored in the reactions of 1-cyano-4-oxo-4H-quinolizine-3-diazonium tetrafluoroborate (1a) and 5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-diazonium tetrafluoroborate (1c) with furan (2a), ferrocene (2g), and benzene (2h). As expected, all six transformations afforded the corresponding arylation products 3i–n as single isomers in 8–40% isolated yields. Next, arylations of thiophene derivatives 2i and 2j with diazonium salts 1b and 1c were investigated. The reaction of 1b with 2,5-dimethylthiophene (2i) gave single arylation product 3o in a 30% yield, while arylation of 1b with 3-methylthiophene (2j) afforded a mixture of three isomeric products 3p, 3′p, and 3″p in a ratio of 65:21:14, respectively. Somewhat expectedly, the reaction of 5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-diazonium tetrafluoroborate (1c) with 2,5-dimethylthiophene (2i) gave a single arylation product of 3q in a 17% yield. Finally, the reaction scope was expanded with another diazonium salt, 4-oxo-7-phenyl-4H-pyrimido[1,2-b]pyridazine-3-diazonium tetrafluoroborate (1d).28 Treatment of 1d with excess furan (2a) under standard conditions gave the expected product 3r in a 52% yield. It is also worth mentioning that attempted arylations of 1b with 1H-indole, 1-methyl-1H-indole, and 1-methyl-1H-pyrrole produced black semi-solid polymeric products and not the desired arylated compounds (Scheme 2).

Scheme 2. C–H Arylations of Diazonium Salts 1a–c with Heteroarenes 2a–f, i, j, Ferrocene (2g), and Benzene (2h),

Scheme 2

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Reaction conditions: diazonium salt 1b (0.5 mmol), heteroarene 1a–h (0.5–5.0 mmol), MeCN/H2O (9:1, 2 mL), EY-Na2 (1 mol %), λ = 510 nm, T = 20 °C, and t = 4–21 h. b A mixture of several regioisomers.

A mixture of several regioisomers.

The moderate isolated yields of compounds 3 are consistent with yields reported for photoredox transformations of aryl diazonium salts based on bicyclic and heterocyclic systems. In general, these yields are significantly lower than those obtained in the same reactions performed with analogous benzenediazonium salts.24,25,35,36 Formation of the major 2-furyl, 2-thienyl, and 2-pyrrolyl isomers 3a, 3b, 3d, 3f, 3p, and 3r was in agreement with the regioselectivity in closely related arylation reactions, while loss of selectivity in reactions with benzofuran (2c) and benzothiophene (2e) was somewhat surprising.25 The regioselective arylation of furan and thiophene derivatives at C(2) is explainable by a large HOMO coefficient of C(2),37 which directs the attack of a heteroaryl radical to this position.38

2.2. Structure Determination

The structures of novel compounds 3a–g, 3i, 3j, 3l, 3m, and 3p–r were determined by spectroscopic methods [IR, NMR spectroscopy (1H- and 13C-NMR, COSY, HSQC, HMBC, and NOESY spectroscopy), and MS-HRMS] and by elemental analyses for C, H, and N. Physical and spectral data of known arylation products 3h,6,19,203k,39 and 3n(40) were in agreement with the literature data. Ratios of isomers in arylation products 3b/3′b and 3f/3′f were determined from the relative intensities of well-resolved characteristic signals in their 1H-NMR spectra.34 The structures of 3b and 3′b and assignments of signals for protons and carbon nuclei of each isomer in their 1H- and 13C-NMR spectra were determined by COSY, HSQC, HMBC, and NOESY spectroscopy (see the Supporting Information for details).34 The structure of compound 3n was also determined by X-ray diffraction (Figure S21).34 The arylation products 3a–f, 3h, 3i, 3k, 3l, and 3n–r also showed fluorescence upon excitation with UV light, both in solution and in the solid state (Figures S14 and S15), whereas the ferrocenyl-substituted compounds 3g, 3j, and 3m were not fluorescent.34

2.3. Elucidation of the Reaction Mechanism

Several recent studies have shown that photocatalytic C–H arylations of aryldiazonium salts proceed via a radical mechanism.25,33,38,41 The initial reactive species is an aryl radical intermediate formed by SET from the excited state of the catalyst to the aryldiazonium cation to give the corresponding nitrogen-centered radical, followed by the elimination of nitrogen.25,33,38,41 The reaction conditions optimization study (cf. Table 1) already showed that the conversion was lower in the absence of light or/and catalyst (cf. Table 1, entries 11–15), which was in agreement with the postulated radical mechanism. To confirm the radical mechanism, the model reaction 1b + 2a → 3a was performed in the presence of TEMPO as a radical scavenger. As shown in Figure 3, the NMR yield of the arylation product 3a decreased significantly from 77% without TEMPO to 9% with TEMPO. The addition of TEMPO also decreased the yield of 3a when the reaction was carried out under air in a non-degassed solvent (Table S4).34 These results were consistent with the formation of the heteroaryl radical 1b• from the respective diazonium salt 1b (Figure 3).

Figure 3.

Figure 3

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Effect of TEMPO on NMR yields of 3a in the model reaction (1b + 2a → 3a).

Next, the kinetic profiles for the model transformation (1b + 2a → 3a) were determined by 1H NMR under standard conditions (MeCN/H2O = 9:1, 510 nm, 1 mol % of EY-Na2, 20 °C, 48 h) and slightly varied reaction conditions. The results are shown in Figure 4 and Figure S20.34 The fastest reaction rate and the highest conversion were determined under standard photocatalytic conditions, which gave an NMR yield of 74% for 3a after 3 h (Figure 4, green line), whereas the reaction rate and yield decreased in the absence of EY-Na2 (62% after 3 h, Figure 4, blue line). Although the thermal reaction at 20 °C was initially very slow, the reaction rate gradually increased, reaching 55% NMR yield after 48 h (Figure S20, black line). The thermal reaction proceeded faster at 50 °C, giving 3a in 46% yield after 3 h (Figure 4, red line).34 Notably, only the photocatalytic reaction showed a logarithmic kinetic profile (Figure 4, green line), while sigmoidal kinetic profiles were obtained for the other three reactions (Figure S20, black line and Figure 4, blue and red line). The logarithmic kinetic profile of the photocatalytic transformation in the presence of EY-Na2 (Figure 4, green line) is consistent with the photocatalytic radical reaction mechanism. The sigmoidal kinetic profiles of the reactions in the absence of EY-Na2 suggest an autocatalytic or radical-chain reaction mechanism. Since 3a does not absorb light at wavelengths above 450 nm (Figure S13),34 autocatalysis by product 3a was ruled out. On the other hand, the sigmoidal kinetic profiles are consistent with the radical-chain reaction mechanism.38,41 This is possible because aryl radicals are generated from the respective aryl diazonium salts by the action of mild bases even under non-reducing thermal conditions,42 for example, by the use of pyridine or tertiary amines.43 In the model reaction (1b + 2a → 3a), the ring nitrogen atoms in diazonium salts 1 and in product 3 can act as weak tertiary amine bases (Figure S20, black line and Figure 4, red line).34

Figure 4.

Figure 4

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Zoomed kinetic profiles of model transformation 1b + 2a → 3a within the first 3 h under photochemical conditions in the presence (—) or absence (—) of EY-Na2 and under thermal conditions in the absence of EY-Na2 at 20 °C (—) and 50 °C (—).

The above results support the radical mechanism of photocatalytic C–H arylation and are in line with the literature data for related photocatalytic C–H arylations.25 On the basis of our results and related literature examples,25,33,38,41–43 a plausible mechanism for photocatalytic arylation of title heteroaryl diazonium salts 1 with (hetero)arenes 2 is proposed (Scheme 3). The general structures of diazonium salts 1, (hetero)arenes 2, and intermediates 1•, 3•, and 3+ are presented using 4-oxo-4H-pyrido[1,2-a]pyrimidine and furan as representative scaffolds. The reaction starts with light-promoted SET from EY-Na2* to heteroaryl diazonium salt 1, followed by homolytic cleavage of the C–N bond and elimination of dinitrogen gas to generate the heteroaryl radical 1•. To a smaller extent, heteroaryl radical 1• is also generated thermally with the assistance of another molecule of 1 or 3, which act as weak bases.42,43 The addition of 1• to heteroarene 2 generates the radical intermediate 3•, which is then oxidized with EY-Na2 radical cation (EY-Na2•+, path A) and/or with diazonium salt 1 (path B) into the corresponding carbocation intermediate 3+. Deprotonation of carbocation 3+ then gives the final product 3. Notably, path A is a part of a photocatalytic cycle, whereas path B represents the competitive radical-chain reaction process (Scheme 3).

Scheme 3. Plausible Reaction Mechanism Consisting of Photocatalytic C–H Arylation of Diazonium Salts 1 with Heteroarenes 2 Catalyzed by EY-Na2 and Product 3 (Path A) and Radical-Chain C–H Arylation of Diazonium Salts 1 with Heteroarenes 2 (Path B).

Scheme 3

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3. Conclusions

A series of novel 3-(hetero)aryl-substituted 4-oxo-4H-quinolizine and 4-oxo-4H-pyrido[1,2-a]pyrimidine derivatives 3a–n were prepared by visible light-promoted photoredox arylation of the corresponding 4-oxo-4H-quinolizine-3- (1a), 4-oxo-4H-pyrido[1,2-a]pyrimidine-3- (1b), 5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-diazonium tetrafluoroborate (1c), and 4-oxo-7-phenyl-4H-pyrimido[1,2-b]pyridazine-3-diazonium tetrafluoroborate (1d) with heteroarenes 2a–f, i–k, ferrocene (2g), and benzene (2h). Title reactions are the rare examples of the use of heteroaryldiazonium salts in photoredox chemistry in general, while the photocatalytic C–H heteroarylation using quinolizinone-, azaquinolizinone-, or azolo-fused 4-pyrimidinone-diazonium salts is, to our knowledge, unprecedented. This synthetic method has a broad substrate scope, takes place at room temperature, and does not require a transition-metal catalyst. Although typically isolated yields have been moderate (up to 63%), the yields obtained with furan, pyrrole, and thiophene derivatives are comparable to those obtained in related C–H arylations with aryldiazonium salts (around 60%).25,33,36 On the other hand, C–H arylations have also been successful with ferrocene and led to the first examples of ferrocenyl-substituted quinolizinone- and azaquinolizinone-derivatives. Therefore, photocatalytic C–H arylation of title diazonium salts is a simpler and milder alternative to known methods and could become a useful synthetic tool for the preparation of 3-(hetero)aryl-substituted azino- and azolo-fused 4-pyridones and 4-pyrimidones with bridgehead nitrogen atoms - a class of compounds of particular interest due to their biological activities and optical properties.

4. Experimental Section

4.1. General Methods

Photocatalytic transformations were carried out on a custom-made photoreactor using LED illumination, magnetic stirring, and a cooling block to sustain a reaction temperature of 20 °C (see the Supporting Information for details).34 Melting points were determined on a Kofler micro hot stage and on an automated melting point system. The NMR spectra were recorded in CDCl3 and DMSO-d6 using TMS as the internal standard on a 500 or 600 MHz instrument at 500 and 600 MHz for 1H and at 125 and 150 MHz for the 13C nucleus, respectively. Mass spectra were recorded on a TOF LC/MS spectrometer and IR spectra on a FTIR ATR spectrophotometer. Microanalyses were performed by combustion analysis on a CHN analyzer. Column chromatography (CC) and FC were performed on neutral alumina (particle size: 0.035–0.070 mm).

Heteroarenes 2a–f, ferrocene (2g), benzene (2h), and EY-Na2 are commercially available. 1-Cyano-4-oxo-4H-quinolizine-3-diazonium tetrafluoroborate (1a),26 4-oxo-4H-pyrido[1,2-a]pyrimidine-3-diazonium tetrafluoroborate (1b),27 5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-diazonium tetrafluoroborate (1c),29 and 4-oxo-7-phenyl-4H-pyrimido[1,2-b]pyridazine-3-diazonium tetrafluoroborate (1d)28 were prepared following the literature procedures.

4.2. General Procedure for the Photocatalytic Arylation of Heteroaryl Diazonium Tetrafluoroborates 1a–c

4.2.1. Synthesis of Heteroaryl-Substituted Quinolizinones, Pyrido[1,2-a]pyrimidinones, and Thiazolo[3,2-a]pyrimidinones 3a–n

A 5 mL vial with a screw cap and septum was charged with diazonium tetrafluoroborate 1 (0.5 mmol), heteroarene 2 (0.5–5 mmol), EY-Na2 (3.5 mg, 5 μmol), acetonitrile (1.8 mL), and water (0.2 mL). The vial was stopped, carefully degassed, and purged with nitrogen using the freeze–pump–thaw technique. Then, the vial was mounted into a photoreactor and irradiated with green light (510 nm) at 20 °C for 4–21 h. The reaction mixture was purified by CC or FC (neutral alumina, ethyl acetate/petroleum ether). Fractions containing the product were combined and evaporated in vacuo to give the arylation product 3.

4.2.1.1. 3-(Furan-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3a)

From diazonium salt 1b (130 mg, 0.5 mmol) and furan (2a) (365 μL, 5 mmol), 4 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 67 mg (63%) of yellow solid; mp 204–206 °C. 1H NMR (500 MHz, CDCl3): δ 9.18 (dt, J = 7.2, 1.2 Hz, 1H), 8.92 (s, 1H), 7.81–7.65 (m, 2H), 7.51 (dd, J = 1.8, 0.8 Hz, 1H), 7.31 (dd, J = 3.4, 0.8 Hz, 1H), 7.20 (ddd, J = 7.2, 5.6, 2.5 Hz, 1H), 6.56 (dd, J = 3.4, 1.8 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 154.2, 149.5, 149.0, 147.9, 141.9, 135.1, 127.4, 126.8, 116.1, 112.1, 110.5, 108.9. m/z (HRMS); found, 213.0654 (MH+). C12H9N2O2 requires m/z = 213.0659. Anal. Calcd for C12H8N2O2: C, 67.92; H, 3.80; N, 13.20. Found: C, 67.70; H, 3.42; N, 13.00. νmax (ATR): 3110, 2916, 1687 (C=O), 1632 (C=O), 1476, 1334, 1255, 1087, 1005, 814, 744 cm–1.

4.2.1.2. 3-(Thiophen-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3b) and 3-(Thiophen-3-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3′b)

From diazonium salt 1b (130 mg, 0.5 mmol) and thiophene (2b) (200 μL, 2.5 mmol), 19 h, CC (ethyl acetate). Yield: 60 mg (53%) of yellow solid; mp 195–197 °C; 3b/3′b = 81:19. 1H NMR (500 MHz, CDCl3): δ major isomer 3b: 9.21 (dt, J = 7.2, 1.2 Hz, 6 H), 8.87 (s, 2 H), 7.76–7.67 (m, 8 H, 9 H, 3′ H), 7.41 (dd, J = 5.2, 1.1 Hz, 5′ H), 7.22 (ddd, J = 7.1, 6.1, 1.9 Hz, 7 H), 7.15 (dd, J = 5.1, 3.7 Hz, 4′ H); minor isomer 3′b: 9.21 (dt, J = 7.2, 1.2 Hz, 6 H), 8.75 (s, 2 H), 8.23 (dd, J = 3.0, 1.3 Hz, 2′ H), 7.76–7.67 (m, 8 H, 9 H), 7.63 (dd, J = 5.1, 1.3 Hz, 4′ H), 7.41 (dd, J = 5.2, 3.1 Hz, 5′ H), 7.19 (ddd, J = 7.2, 6.1, 1.6 Hz, 7 H). 13C{1H} NMR (126 MHz, CDCl3): δ major isomer 3b: 155.4, 150.1, 149.6, 135.3, 135.3, 127.7, 127.1, 126.7, 126.2, 124.1, 116.3, 112.0; minor isomer 3′b: 156.2, 151.5, 149.9, 135.7, 134.1, 127.6, 126.6, 125.9, 125.5, 123.9, 115.9, 112.5. 1H NMR (500 MHz, DMSO-d6): δ major isomer 3b: 9.12 (dq, J = 7.1, 0.8 Hz, 6-H), 9.05 (s, 2-H), 7.97 (dd, J = 8.6, 6.7, 1.5 Hz, 8 H), 7.86 (dd, J = 3.7, 1.1 Hz, 3′ H), 7.79 (dt, J = 8.7, 1.1 Hz, 9 H), 7.57 (dd, J = 5.1, 1.0 Hz, 5′ H), 7.46 (td, J = 7.0, 1.4 Hz, 7 H), 7.16 (dd, J = 5.1, 3.7 Hz, 4′ H); minor isomer 3′b: 9.13 (dq, J = 7.1, 0.8 Hz, 6 H), 8.94 (s, 2 H), 8.33 (dd, J = 3.0, 1.2 Hz, 2′ H), 7.96 (ddd, J = 8.6, 6.7, 1.5 Hz, 8 H), 7.84 (dd, J = 5.1, 1.2 Hz, 4′ H), 7.75 (dt, J = 8.6, 1.0 Hz, 9 H), 7.64 (dd, J = 5.1, 3.0 Hz, 5′ H), 7.42 (td, J = 7.0, 1.3 Hz, 7 H). 13C{1H} NMR (126 MHz, DMSO-d6): δ major isomer 3b: 154.6, 150.0, 149.3, 136.8, 135.5, 127.5, 126.9, 126.5, 126.2, 123.5, 117.3, 110.4; minor isomer 3′b: 155.4, 151.7, 149.6, 136.7, 134.5, 127.4, 126.3, 126.2, 125.8, 123.1, 116.9, 110.9. m/z (HRMS); found, 229.0428 (MH+). C12H9N2OS requires m/z = 229.0430. νmax (ATR): 3080, 2922, 1655 (C=O), 1628 (C=O), 1478, 1368, 1123, 1075, 889, 800, 759, 731 cm–1.

4.2.1.3. 3-Benzo[b]furanyl-4H-pyrido[1,2-a]pyrimidin-4-one (a Mixture of Isomers) (3c)

From diazonium salt 1b (130 mg, 0.5 mmol) and benzofuran (2c) (83 μL, 0.75 mmol), 19 h, CC (ethyl acetate). Yield: 35 mg (27%) of yellow-green solid; mp 130–205 °C; ratio of isomers = 37:25:18:12:8. 1H NMR (500 MHz, CDCl3): δ 9.27–9.22 (m, 1H), 9.14, 8.87, 8.62, 8.60, and 8.59 (5s, 8:25:18:12:37, 1H), 8.06–8.03, 7.83–7.19, and 6.86–6.79 (3m, 8:89:3, 8H). 13C{1H} NMR (126 MHz, CDCl3): δ 157.1, 156.9, 156.5, 156.4, 155.2, 155.1, 154.8, 154.6, 154.5, 154.3, 154.1, 153.0, 153.0, 152.5, 150.9, 150.6, 150.5, 150.4, 150.1, 149.9, 145.7, 145.5, 145.0, 144.9, 136.0, 135.9, 135.6, 135.5, 130.6, 129.5, 128.0, 127.9, 127.8, 127.7, 127.7, 127.7, 127.6, 127.1, 126.9, 126.9, 126.6, 126.6, 125.5, 125.1, 124.6, 124.4, 123.8, 123.4, 123.0, 123.0, 121.6, 121.3, 121.1, 121.0, 118.7, 117.2, 116.4, 116.3, 116.0, 115.9, 115.8, 112.9, 111.7, 111.4, 111.2, 110.8, 108.2, 106.9, 106.7, 106.7, 106.5. m/z (HRMS); found, 263.0807 (MH+). C16H11N2O2 requires m/z = 263.0815. Anal. Calcd for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68. Found: C, 72.93; H, 3.53; N, 10.53. νmax (ATR): 3090, 3034, 1677 (C=O), 1628 (C=O), 1486, 1293, 1256, 1119, 1071, 804, 790, 740 cm–1.

4.2.1.4. 3-(5-Methylfuran-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3d)

From diazonium salt 1b (130 mg, 0.5 mmol) and 2-methylfuran (2d) (450 μL, 5 mmol), 19 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 28 mg (25%) of yellow–orange solid; mp 192–194 °C; ratio of isomers = 97:3. 1H NMR (500 MHz, CDCl3): δ 9.16 (dt, J = 7.2, 1.2 Hz, 1H), 8.88 (s, 1H), 7.71–7.64 (m, 2H), 7.20 (br d, J = 3.2 Hz, 1H), 7.17 (ddd, J = 7.2, 5.1, 2.9 Hz, 1H), 6.15 (br dq, J = 3.2, 1.0 Hz, 1H), 2.41 (br d, J = 1.0 Hz, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 154.1, 152.1, 149.0, 148.2, 146.1, 134.6, 127.3, 126.7, 115.9, 111.9, 109.3, 108.3, 13.8. m/z (HRMS); found, 227.0815 (MH+). C13H11N2O2 requires m/z = 227.0815. νmax (ATR): 3102, 2919, 1673 (C=O), 1627 (C=O), 1570, 1485, 1366, 1256, 1106, 1018, 890, 773 cm–1.

4.2.1.5. 3-(Benzo[b]thiophenyl)-4H-pyrido[1,2-a]pyrimidin-4-one (a Mixture of Isomers) (3e)

From diazonium salt 1b (130 mg, 0.5 mmol) and benzo[b]thiophene (2e) (100 mg, 0.75 mmol), 20 h, CC (ethyl acetate/petroleum ether = 3:1). Yield: 46 mg (32%) of yellow solid; mp 93–193 °C; ratio of isomers = 21:21:20:19:11:8. 1H NMR (500 MHz, CDCl3): δ 9.26–9.07 (m, 1H), 8.89, 8.72, 8.66, 8.64, 8.63, and 8.55 (6s, 21:8:20:19:11:21, 1H), 8.42–8.12, 7.98–7.64, 7.58–7.27, 7.25–7.13, and 6.47–6.45 (5m, 2:12:31:48:7, 8H). 13C{1H} NMR (126 MHz, CDCl3): δ 157.0, 156.9, 156.7, 156.6, 156.1, 155.3, 154.8, 154.4, 154.1, 153.7, 153.0, 151.5, 151.2, 151.1, 150.8, 150.6, 150.6, 150.1, 140.4, 140.3, 140.2, 140.1, 140.0, 139.9, 139.5, 139.2, 139.1, 138.5, 137.9, 136.3, 136.2, 136.1, 136.0, 135.9, 135.7, 135.6, 130.4, 130.3, 129.8, 129.5, 129.1, 128.0, 127.8, 127.8, 127.8, 127.7, 127.4, 127.2, 126.9, 126.7, 126.7, 126.6, 126.6, 126.6, 126.6, 126.5, 126.5, 126.4, 126.0, 125.9, 124.8, 124.7, 124.5, 124.5, 124.4, 124.3, 124.3, 124.2, 124.2, 123.7, 123.6, 123.6, 123.5, 123.3, 122.9, 122.9, 122.5, 122.5, 122.5, 122.0, 121.9, 117.2, 116.9, 116.7, 116.5, 116.0, 116.0, 115.9, 115.9, 115.6, 112.6, 111.6, 104.8. m/z (HRMS); found, 279.0588 (MH+). C16H11N2OS requires m/z = 279.0587. Anal. Calcd for C16H10N2OS requires C, 69.05; H, 3.62; N, 10.07. Found: C, 68.79; H, 3.45; N, 9.99. νmax (ATR): 3097, 2917, 2849, 1667 (C=O), 1628 (C=O), 1563, 1471, 1333, 1292, 1122, 1069, 891, 757, 697 cm–1.

4.2.1.6. tert-Butyl 2-(4-Oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-pyrrole-1-carboxylate (3f) and tert-Butyl 3-(4-Oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-1H-pyrrole-1-carboxylate (3′f)

From diazonium salt 1b (130 mg, 0.5 mmol) and N-Boc-pyrrole (2f) (167 μL, 1 mmol), 4 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 74 mg (47%) of pale yellow solid; mp 193–195 °C; 3f:3′f = 93:7. 1H NMR (500 MHz, CDCl3): δ major isomer 3f: 9.11 (ddd, J = 7.2, 1.6, 0.9 Hz, 1H), 8.35 (s, 1H), 7.72 (ddd, J = 9.0, 6.5, 1.6 Hz, 1H), 7.66 (ddd, J = 9.0, 1.5, 0.9 Hz, 1H), 7.42 (dd, J = 3.3, 1.8 Hz, 1H), 7.15 (ddd, J = 7.2, 6.5, 1.5 Hz, 1H), 6.31 (dd, J = 3.3, 1.8 Hz, 1H), 6.27 (t, J = 3.3 Hz, 1H), 1.40 (s, 9H). minor isomer 3′f: 9.18 (dt, J = 7.2, 1.2 Hz, 1H), 8.68 (s, 1H), 8.20 (t, J = 1.9 Hz, 1H), 7.68–7.70 (m, 2H), 7.36 (dd, J = 3.4, 2.2 Hz, 1H), 7.18 (ddd, J = 7.2, 5.2, 2.8 Hz, 1H), 6.73 (dd, J = 3.4, 1.7 Hz, 1H), 1.63 (s, 9H). 13C{1H} NMR (126 MHz, CDCl3): δ major isomer 3f: 156.8, 152.3, 150.9, 149.0, 135.5, 127.4, 127.2, 126.5, 123.1, 115.6, 115.4, 112.9, 110.6, 83.4, 27.7; minor isomer 3′f: 155.8, 150.1, 149.3, 148.8, 134.7, 127.3, 126.6, 120.7, 119.9, 119.7, 115.8, 111.6, 109.5, 83.9, 28.0. m/z (HRMS); found, 312.1337 (MH+). C17H18N3O3 requires m/z = 312.1343. νmax (ATR): 3105, 2982, 2930, 749 (C=O), 1674 (C=O), 1636 (C=O), 1495, 1331, 1306, 1254, 1139, 1054, 904, 844, 765, 721 cm–1.

4.2.1.7. 3-Ferrocenyl-4H-pyrido[1,2-a]pyrimidin-4-one (3g)

From diazonium salt 1b (130 mg, 0.5 mmol) and ferrocene (2g) (93 mg, 0.5 mmol), 19 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 22 mg (13%) of red solid; mp 202–204 °C. 1H NMR (500 MHz, CDCl3): δ 9.17 (ddd, J = 7.2, 1.5, 0.9 Hz, 1H), 8.58 (s, 1H), 7.69 (ddd, J = 9.0, 6.5, 1.5 Hz, 1H), 7.64 (ddd, J = 9.0, 1.5, 0.9 Hz, 1H), 7.15 (ddd, J = 7.2, 6.5, 1.5 Hz, 1H), 5.04 (t, J = 1.9 Hz, 2H), 4.39 (t, J = 1.9 Hz, 2H), 4.11 (s, 5H). 13C{1H} NMR (126 MHz, CDCl3): δ 155.7, 150.4, 149.5, 134.5, 127.1, 126.7, 116.3, 115.7, 79.2, 69.5, 69.1, 67.5. m/z (HRMS); found, 331.0517 (MH+). C18H15FeN2O requires m/z = 331.0528. νmax (ATR): 3083, 2917, 1670 (C=O), 1633 (C=O), 1495, 1459, 1381, 1257, 1100, 809, 789 cm–1.

4.2.1.8. 3-Phenyl-4H-pyrido[1,2-a]pyrimidin-4-one (3h)

From diazonium salt 1b (130 mg, 0.5 mmol) and benzene (2h) (225 μL, 2.5 mmol), 21 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 30 mg (27%) of pale-green solid; mp 168–170 °C, lit.19 mp 167–169 °C. 1H NMR (500 MHz, CDCl3): δ 9.21 (ddd, J = 7.2, 1.6, 0.9 Hz, 1H), 8.56 (s, 1H), 7.85–7.78 (m, 2H), 7.75 (ddd, J = 9.0, 6.5, 1.6 Hz, 1H), 7.70 (dt, J = 9.0, 1.5 Hz, 1H), 7.47 (br t, J = 7.7 Hz, 2H), 7.37 (tt, J = 7.4, 1.3 Hz, 1H), 7.20 (ddd, J = 7.2, 6.5, 1.5 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 156.8, 153.0, 150.7, 135.7, 134.3, 128.6, 128.6, 127.8, 127.7, 126.6, 117.1, 115.9. m/z (HRMS); found, 223.0863 (MH+). C14H11N2O requires m/z = 223.0866. Anal. Calcd for C14H10N2O·1/8H2O: C, 74.90; H, 4.60; N, 12.48. Found: C, 75.02; H, 4.58; N, 12.25. νmax (ATR): 3133, 2917, 1672 (C=O), 1625 (C=O), 1494, 1472, 1289, 1124, 1074, 899, 774, 696 cm–1. The spectral data are in agreement with the literature.6,19,20

4.2.1.9. 3-(Furan-2-yl)-4-oxo-4H-quinolizine-4-carbonitrile (3i)

From diazonium salt 1a (142 mg, 0.5 mmol) and furan (3a) (365 μL, 5 mmol), 4 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 37 mg (31%) of orange solid; mp 196–198 °C. 1H NMR (500 MHz, CDCl3): δ 9.34 (br dt, J = 7.3, 1.0 Hz, 1H), 8.43 (s, 1H), 8.01 (br dt, J = 8.9, 1.0 Hz, 1H), 7.70 (ddd, J = 8.8, 6.7, 1.2 Hz, 1H), 7.51 (br dd, J = 1.7, 0.6 Hz, 1H), 7.37 (br d, J = 3.4 Hz, 1H), 7.27 (td, J = 7.0, 1.4 Hz, 1H), 6.57 (dd, J = 3.4, 1.8 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 154.0, 148.5, 143.6, 142.6, 133.8, 133.5, 128.9, 123.6, 117.2, 117.1, 112.5, 111.9, 111.1, 85.9. m/z (HRMS); found, 237.0657 (MH+). C14H9N2O2 requires m/z = 237.0659. νmax (ATR): 2218 (C≡N), 1682 (C=O), 1502, 1246, 1013, 744 cm–1.

4.2.1.10. 3-Ferrocenyl-4-oxo-4H-quinolizin-1-carbonitrile (3j)

From diazonium salt 1a (142 mg, 0.5 mmol) and ferrocene (2g) (140 mg, 0.75 mmol), 4 h, CC (ethyl acetate/petroleum ether = 1:3). Yield: 17 mg (10%) of red solid; mp 194–196 °C. 1H NMR (500 MHz, CDCl3): δ 9.30 (br d, J = 7.3 Hz, 1H), 8.04 (s, 1H), 7.93 (br d, J = 8.8 Hz, 1H), 7.66 (ddd, J = 8.8, 6.7, 1.2 Hz, 1H), 7.21 (td, J = 6.9, 1.0 Hz, 1H), 5.04 (t, J = 1.9 Hz, 2H), 4.41 (t, J = 1.9 Hz, 2H), 4.10 (s, 5H). 13C{1H} NMR (126 MHz, CDCl3): δ 155.6, 143.6, 135.4, 132.7, 128.5, 123.6, 120.6, 117.6, 116.8, 85.3, 80.5, 69.7, 69.6, 68.0, 68.0. m/z (HRMS); found, 354.0449 (M+). C20H14FeN2O requires m/z = 354.0456. νmax (ATR): 3118, 3088, 2917, 2950, 2206 (C≡N), 1675 (C=O), 1628 (C=O), 1584, 1504, 1459, 1305, 1247, 1150, 1104, 803, 756 cm–1.

4.2.1.11. 4-Oxo-3-phenyl-4H-quinolizin-4-carbonitrile (3k)

From diazonium salt 1a (142 mg, 0.5 mmol) and benzene (2h) (225 μL, 2.5 mmol), 18 h, CC (ethyl acetate/petroleum ether = 2:3). Yield: 10 mg (8%) of green solid; mp 178–180 °C, lit.39 mp 180–182 °C. 1H NMR (500 MHz, CDCl3): δ 9.36 (br d, J = 7.3 Hz, 1H), 8.05 (s, 1H), 8.01 (br d, J = 8.9 Hz, 1H), 7.79–7.70 (m, 3H), 7.46 (br t, J = 7.6 Hz, 2H), 7.37 (tt, J = 7.4, 1.2 Hz, 1H), 7.27 (td, J = 7.2, 1.3 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 156.8, 145.0, 138.9, 135.8, 134.2, 129.3, 128.7, 128.7, 128.2, 123.4, 120.8, 117.3, 117.0, 85.4. m/z (HRMS); found, 247.0865 (MH+). C16H11N2O requires m/z = 247.0866. νmax (ATR): 2207 (C≡N), 1665 (C=O), 1626, 1587, 1500, 1487, 766, 697 cm–1. The spectral data are in agreement with the literature.39

4.2.1.12. 6-(Furan-2-yl)-5H-thiazolo[3,2-a]pyrimidin-5-one (3l)

From diazonium salt 1c (133 mg, 0.5 mmol) and furan (2a) (365 μL, 5 mmol), 4 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 44 mg (40%) of pale green solid; mp 201–203 °C. 1H NMR (500 MHz, CDCl3): δ 8.60 (s, 1H), 8.11 (d, J = 4.9 Hz, 1H), 7.47 (br dd, J = 1.6, 0.6 Hz, 1H), 7.23 (dd, J = 3.3, 0.6 Hz, 1H), 7.07 (br d, J = 4.9 Hz, 1H), 6.52 (dd, J = 3.3, 1.8 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 160.3, 155.4, 147.5, 147.2, 142.0, 122.4, 112.4, 112.1, 110.5, 110.3. m/z (HRMS); found, 219.0230 (MH+). C10H7N2O2S requires m/z = 219.0223. νmax (ATR): 3122, 2921, 1673 (C=O), 1504, 1477, 1348, 1275, 1162, 1068, 976, 814, 770, 708 cm–1.

4.2.1.13. 6-Ferrocenyl-5H-thiazolo[3,2-a]pyrimidin-5-one (3m)

From diazonium salt 1c (133 mg, 0.5 mmol) and ferrocene (2g) (140 mg, 0.75 mmol), 4 h, CC (ethyl acetate/petroleum ether = 1:3). Yield: 18 mg (11%) of orange-red solid; mp 228–230 °C. 1H NMR (500 MHz, CDCl3): δ 8.25 (s, 1H), 8.08 (d, J = 4.9 Hz, 1H), 7.02 (d, J = 4.9 Hz, 1H), 4.94 (t, J = 1.8 Hz, 2H), 4.35 (t, J = 1.8 Hz, 2H), 4.11 (s, 5H). 13C{1H} NMR (126 MHz, CDCl3): δ 159.9, 156.9, 148.6, 122.3, 117.4, 111.9, 78.6, 73.3, 69.6, 69.2, 67.4. m/z (HRMS); found, 336.0013 (M+). C16H12FeN2OS requires m/z = 336.0020. νmax (ATR): 3104, 2921, 2852, 1658 (C=O), 1505, 1366, 1279, 1081, 927, 801, 723, 658 cm–1.

4.2.1.14. 6-Phenyl-5H-thiazolo[3,2-a]pyrimidin-5-one (3n)

From diazonium salt 1c (133 mg, 0.5 mmol) and benzene (2h) (225 μL, 2.5 mmol), 18 h, CC (ethyl acetate/petroleum ether = 1:2). Yield: 30 mg (27%) of translucent crystalline solid; mp 146–148 °C, lit.40 mp 147–148 °C. 1H NMR (500 MHz, CDCl3): δ 8.23 (s, 1H), 8.12 (d, J = 4.9 Hz, 1H), 7.71 (d, J = 7.1 Hz, 2H), 7.45 (t, J = 7.6 Hz, 2H), 7.37 (tt, J = 7.4, 1.2 Hz, 1H), 7.07 (d, J = 4.9 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 161.8, 157.8, 151.5, 133.5, 128.7, 128.6, 128.1, 122.7, 118.7, 112.1. m/z (HRMS); found, 229.0431 (MH+). C12H9N2OS requires m/z = 229.0430. Anal. Calcd for C12H8N2OS·1/50HBF4: C, 62.66; H, 3.51; N, 12.18. Found: C, 62.87; H, 3.12; N, 11.97. νmax (ATR): 3118, 1653 (C=O), 1501, 1359, 1283, 715, 698, 654 cm–1. Physical data are in agreement with the literature.40

4.2.1.15. 3-(2,5-Dimethylthiophen-3-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3o)

From diazonium salt 1b (130 mg, 0.5 mmol) and 2,5-dimethylthiophene (2i) (115 μL, 1 mmol), 18 h, CC (ethyl acetate/petroleum ether = 1:1). Yield: 38 mg (30%) of yellow solid; mp 128–130 °C. 1H NMR (500 MHz, CDCl3): δ 9.15 (ddd, J = 7.2, 1.3, 0.7 Hz, 1H), 8.34 (s, 1H), 7.73 (ddd, J = 8.1, 6.5, 1.5 Hz, 1H), 7.68 (ddd, J = 8.9, 1.3, 0.7 Hz, 1H), 7.17 (td, J = 7.2, 1.5 Hz, 1H), 6.84–6.82 (br m, 1H), 2.44 (s, 3H), 2.40 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 156.7, 154.0, 150.7, 135.9, 135.6, 135.0, 130.3, 127.7, 127.4, 126.7, 115.8, 113.8, 15.3, 14.4. m/z (HRMS); found, 257.0739 (MH+). C14H13N2OS requires m/z = 257.0743. νmax (ATR): 3101, 2914, 2854, 1669 (C=O), 1632 (C=O), 1494, 1474, 1325, 1236, 1075, 1027, 964, 849, 773, 740, 654 cm–1.

4.2.1.16. 3-(3-Methylthiophen-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3p), 3-(4-Methylthiophen-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3′p), and 3-(4-Methylthiophen-3-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3″p)

From diazonium salt 1b (130 mg, 0.5 mmol) and 3-methylthiophene (2j) (100 μL, 1 mmol), 18 h, CC (ethyl acetate/petroleum ether = 2:3). Yield: 48 mg (40%) of yellow solid; mp 78–130 °C; 3p:3′p:3″p = 65:21:14. 1H NMR (500 MHz, CDCl3): δ major isomer 3p: 9.17 (br d, J = 6.7 Hz, 1H), 8.49 (s, 1H), 7.78–7.72 (m, 1H), 7.72–7.67 (m, 1H), 7.33 (br d, J = 5.1 Hz, 1H), 7.20 (td, J = 7.0, 1.2 Hz, 1H), 6.95 (d, J = 5.1 Hz, 1H), 2.32 (s, 3H); minor isomer 3′p: 9.18 (br d, J = 6.4 Hz, 1H), 8.81 (s, 1H), 7.78–7.72 (m, 1H), 7.72–7.67 (m, 1H), 7.56 (d, J = 0.9 Hz, 1H), 7.20 (td, J = 7.0, 1.2 Hz, 1H), 6.97 (br s, 1H), 2.32 (s, 3H); minor isomer 3″p: 9.18 (br d, J = 6.7 Hz, 1H), 8.38 (s, 1H), 7.78–7.72 (m, 1H), 7.72–7.67 (m, 1H), 7.42 (d, J = 3.3 Hz, 1H), 7.20 (td, J = 7.0, 1.2 Hz, 1H), 7.05–7.03 (m, 1H), 2.26 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ major isomer 3p: 156.5, 154.1, 150.0, 136.3, 136.0, 130.5, 127.9, 126.7, 125.3, 121.9, 116.1, 112.0, 15.6; minor isomers 3′p and 3″p: 156.7, 155.4, 154.1, 153.9, 151.0, 150.6, 149.6, 137.9, 137.7, 135.9, 135.5, 135.3, 135.1, 129.3, 127.8, 127.7, 126.8, 126.7, 125.5, 121.9, 116.4, 115.9, 114.0, 112.2, 15.9, 15.4. m/z (HRMS); found, 243.0588 (MH+). C13H11N2OS requires m/z = 243.0587. νmax (ATR): 3085, 2960, 1657 (C=O), 1627 (C=O), 1483, 1375, 1333, 1125, 1080, 884, 824, 765, 729, 707 cm–1.

4.2.1.17. 6-(2,5-Dimethylthiophen-3-yl)-5H-thiazolo[3,2-a]pyrimidin-5-one (3q)

From diazonium salt 1c (133 mg, 0.5 mmol) and 2,5-dimethylthiophene (2i) (115 μL, 1 mmol), 4 h, CC (ethyl acetate/petroleum ether = 2:3). Yield: 23 mg (17%) of yellow solid; mp 155–157 °C. 1H NMR (500 MHz, CDCl3): δ 8.08 (d, J = 4.9 Hz, 1H), 8.02 (s, 1H), 7.04 (d, J = 4.9 Hz, 1H), 6.76 (br s, 1H), 2.43 (s, 3H), 2.38 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3): δ 161.6, 157.6, 152.4, 135.9, 135.1, 129.3, 127.4, 122.6, 115.0, 112.0, 15.3, 14.3. m/z (HRMS); found, 263.0302 (MH+). C12H11N2OS2 requires m/z = 263.0307. νmax (ATR): 3069, 2918, 2854, 1650 (C=O), 1496, 1476, 1435, 1345, 1218, 1136, 1023, 844, 777, 742, 675 cm–1.

4.2.1.18. 3-(Furan-2-yl)-7-phenyl-4H-pyrimido[1,2-b]pyridazin-4-one (3r)

From diazonium salt 1d (169 mg, 0.5 mmol) and furan (2a) (365 μL, 5 mmol), 18 h, CC (ethyl acetate/petroleum ether = 3:2). Yield: 75 mg (52%) of yellow solid; mp 216–218 °C. 1H NMR (500 MHz, CDCl3): δ 8.83 (s, 1H), 8.17–8.05 (m, 2H), 7.93 (d, J = 9.4 Hz, 1H), 7.87 (d, J = 9.4 Hz, 1H), 7.60–7.42 (m, 5H), 6.57 (dd, J = 3.4, 1.8 Hz, 1H). 13C{1H} NMR (126 MHz, CDCl3): δ 154.7, 153.4, 147.4, 146.8, 146.5, 142.7, 135.2, 133.9, 131.5, 129.4, 127.6, 124.9, 114.3, 112.7, 112.5. m/z (HRMS); found, 290.0922 (MH+). C17H12N2O2 requires m/z = 290.0924. νmax (ATR): 3106, 1699 (C=O), 1540, 1474, 1346, 1328, 1251, 1007, 838, 778, 758, 726, 688 cm–1.

4.2.2. Synthesis of 3-(Furan-2-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (3a) on a Larger Scale

A 16 mL vial with a screw cap and septum was charged with diazonium tetrafluoroborate 1b (520 mg, 2.0 mmol), furan 2 (1.46 mL, 20 mmol), EY-Na2 (14 mg, 20 μmol), acetonitrile (7.2 mL), and water (0.8 mL). The vial was stopped, carefully degassed, and purged with nitrogen using the freeze–pump–thaw technique. Then the vial was mounted into a photoreactor and irradiated with green light (510 nm) at 20 °C for 4 h. The reaction mixture was purified by CC (neutral alumina, ethyl acetate/petroleum ether = 1:1). Fractions containing the product were combined and evaporated in vacuo to give 3a. Yield: 241 mg (57%) of yellow solid with physical and spectral data in agreement with the data of 3a obtained on a 0.5 mmol scale (see Section 4.2.1).

4.2.3. Preparation of Single Crystals of Compound 3n

A 1 mL vial was charged with compound 3n (5 mg) and CDCl3 (150 μL). Then, the 1 mL vial containing a solution of 3n in CDCl3 was placed into a 5 mL vial containing petroleum ether (450 μL). The outer vial (5 mL vial) was stopped and left to stand at room temperature for 3 days under vapor diffusion conditions. Since no crystal growth was observed after 3 days, the stopper was punctured several times with a syringe needle to allow slow evaporation of the solvents. After standing at room temperature for two more days, the solvents evaporated completely to leave a translucent crystalline residue that contained single crystals of 3n. One of these crystals was then selected and used for X-ray diffraction analysis.

Acknowledgments

The financial support from the Slovenian Research Agency through grant P1-0179 is gratefully acknowledged. NMR and LC-HRMS characterizations and microanalyses of compounds were performed at the Centre for Research Infrastructure at the Faculty of Chemistry and Chemical Technology, University of Ljubljana (IC UL FCCT).

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.3c01517.

  • Experimental details (reaction setup), copies of 1H NMR, 13C NMR, and 2D NMR spectra, copies of IR spectra, structure determination by NMR, elucidation of the reaction mechanism, and X-ray diffraction analysis data for 3n (PDF)

The authors declare no competing financial interest.

Dedication

This work is dedicated to Professor Emeritus Branko Stanovnik, University of Ljubljana, on the occasion of his 85th birthday.

Supplementary Material

jo3c01517_si_001.pdf (3.4MB, pdf)

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Associated Data

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Supplementary Materials

jo3c01517_si_001.pdf (3.4MB, pdf)

Data Availability Statement

The data underlying this study are available in the published article and its Supporting Information.

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