Visible-Light-Driven Decarboxylative Coupling of 2H-Indazoles with α-Keto Acids without Photocatalysts and Oxidants

Abstract

An efficient synthesis of functionalized 3-acyl-2H-indazoles via visible-light-induced self-catalyzed energy transfer was developed. This method utilized a self-catalyzed energy transfer process between 2H-indazoles and α-keto acids, offering advantages like absence of photosensitizers, metal catalysts, and strong oxidants, broad substrate compatibility, and operational simplicity under mild conditions.

Introduction

Nitrogen-containing heterocycles play an essential role in the molecular structures of natural compounds,¹ pharmaceuticals,² and various biologically active substances.³ 2H-indazole derivatives are known for their diverse range of biological activities, including antitumor,⁴ antibacterial,⁵ anti-inflammatory,⁶ and anticancer⁷ properties. This makes them valuable components in the development of pharmaceuticals and other biologically active compounds. Thus, the pursuit of environmentally friendly and highly efficient methods for synthesizing functionalized 2H-indazoles has become a focal point in the field of synthetic methodology.⁸

In particular, C3-acylated 2H-indazoles have been used as polymerase inhibitors⁹ and demonstrated notable value in pharmacology.¹⁰ While several methods for the synthesis of 3-acyl-2H-indazoles have been developed, these methods often involve the use of transition metals, environmentally unfriendly stoichiometric oxidants, or high temperature conditions.¹¹ These conditions lead to the generation of chemical wastes and significantly raise the overall manufacturing cost. For example, Liu and co-workers introduced a Ag-catalyzed [3 + 2] cycloaddition for the synthesis of 3-acyl-2H-indazoles utilizing benzynes and diazocarbonyl compounds (Figure 1Aa).¹² Kim and co-workers reported a Rh(III)-catalyzed C–H functionalization of azobenzene with keto aldehydes (Figure 1Ab).¹³ You and co-workers developed a tandem Rh(III)-catalyzed C–H alkylation/intramolecular decarboxylative cyclization method using azoxy compounds and diazoesters (Figure 1Ac).¹⁴ In addition to the above-mentioned cycloaddition methods, alternative approaches to the synthesis of 3-acyl-2H-indazoles involve the direct addition of acyl radicals to 2H-indazoles. In these cases, acyl radicals could be generated from various acyl precursors, such as α-keto acids¹⁵ and aldehydes.¹⁶ For example, in the presence of strong oxidants (e.g., Na₂S₂O₈ and TBHP), silver nitrate¹⁷ and NiCl₂¹⁸ have been employed for the C-3 substituted acyl 2H-indazoles using α-keto acids and aldehydes, respectively (Figure 1Bd,Be). Recently, a metal free method was developed by using aldehyde and di-tert-butylperoxide (DTBP) at a high temperature of 120 °C (Figure 1Bf).¹⁹ To the best of our knowledge, a mild C-3 acylation of 2H-indazoles at room temperature without the use of transition metals, oxidants, and photosensitizers has never been reported.

Figure 1.

Representative examples of synthesis of 3-acyl-2H-indazoles and this work.

Building on our continued efforts to develop environmentally friendly and efficient methods for the synthesis of functionalized N-heterocycles,²⁰ herein, we reported a visible-light-induced self-catalyzed decarboxylative coupling reaction of 2H-indazoles and α-keto acids (Figure 1C). Notably, this method did not require the use of photocatalysts or oxidants under mild conditions.

Results and Discussion

We commenced our study by optimizing reaction conditions, employing a model reaction of 2-phenyl-2H-indazole (1a) with 2-oxo-2-phenylacetic acid (2a). Table 1 summarizes the results of optimization experiments. Initially, degassed acetonitrile (MeCN) was selected as the solvent, and 1a and 2a were irradiated with a 6 W LED (380–385 nm) for a duration of 10 h under a N₂ atmosphere. Pleasingly, this initial experiment yielded our desired product 3aa in 43% yield (Table 1, entry 1). Further optimization was carried out to determine the optimal conditions. Various solvents were systematically investigated, including 1,4-dioxane, dichloroethane (DCE), dimethyl sulfoxide (DMSO) (Table 1, entries 2–4). Among these solvents, MeCN emerged as the most effective solvent.

Table 1. Optimization of Reaction Conditions^g.

entry	2a (equiv)	light source (nm)	additive	solvent	yield (%)a
1	2.0	380–385		MeCN	43
2	2.0	380–385		1,4-dioxane	14
3	2.0	380–385		DCE	26
4	2.0	380–385		DMSO	N.R.
5	3.0	380–385		MeCN	50
6	4.0	380–385		MeCN	57
7	5.0	380–385		MeCN	62
8	6.0	380–385		MeCN	62
9	5.0	380–385	4CzIPN (5 mol %)	MeCN	60
10	5.0	380–385	5 Å-MS (50 mg)	MeCN	54
11	5.0	380–385	DTBP (2 equiv)	MeCN	60
12	5.0	380–385	K2S2O8 (2 equiv)	MeCN	56
13b	5.0	380–385		MeCN	57
14c	5.0	380–385		MeCN	67
15d	5.0	380–385		MeCN	61
16c	5.0	380–385	tBuOK (2 equiv)	MeCN	41
17c	5.0	380–385	K2CO3 (2 equiv)	MeCN	38
18c	5.0	360–365		MeCN	57
19c	5.0	390–395		MeCN	50
20c	5.0	405–410		MeCN	56
21c	5.0	420–425		MeCN	68
22c	5.0	450–455		MeCN	50
23c	5.0	420–425		MeCN/HFIP (1:1)	52
24c	5.0	420–425		MeCN/HFIP (3:1)	71
25c	5.0	420–425		MeCN/HFIP (5:1)	68
26c	5.0	420–425		MeCN/TFA (3:1)	6
27c	5.0	420–425		MeCN/TfOH (3:1)	N.R.
28c,e	5.0	420–425		MeCN/HFIP (3:1)	45
29c,f	5.0	420–425		MeCN/HFIP (3:1)	71

^aYield of 3aa was determined by GC using docosane as internal standard. N.R.: no reaction.

^bSolvent (3.0 mL).

^cSolvent (4.0 mL).

^dSolvent (5.0 mL).

^eReaction time was 6 h.

^fReaction time was 16 h.

^gReaction conditions: 1a (0.2 mmol), 2a (amount as specified), solvent as specified (2.0 mL), room temperature, nitrogen atmosphere, 10 h.

Furthermore, the influence of the ratio between 1a and 2a on the reaction was explored. As demonstrated in Table 1 (entries 5–7), increasing the ratio between 1a and 2a from 1:2 to 1:5 led to an enhanced yield of 3aa from 43 to 62%. However, when the ratio was further increased to 1:6 (Table 1, entry 8), there was no further improvement in the yield of 3aa. Therefore, the optimal ratio between 1a and 2a was identified as 1:5. It was known that α-keto acids (e.g., 2a) could undergo decarboxylation under light irradiation, leading to the formation of acyl radicals.²¹ Indeed, during the reaction optimization, benzil was identified as one of the byproducts (details see Figure 4a), which could be generated from acyl radicals. It was found that the concentration of starting materials could also affect the efficiency of reaction. As indicated in Table 1 (entries 13–15), the amount of solvent utilized in the reaction (2–5 mL) also had an impact on the performance of the reaction, with the optimal solvent amount of 4 mL for 0.2 mmol scale.

Figure 4.

Organic intermediates determined by GC-MS and the proposed mechanism.

It has been reported that the addition of oxidants (e.g., K₂S₂O₈, organic peroxides) and photoinitiators could help the generation of free acyl radicals from 2a, facilitating subsequent free radical coupling reactions.²² Thus, the addition of various additives such as photoinitiators (4CzIPN), oxidants (e.g., K₂S₂O₈, DTBP), bases (^tBuOK, K₂CO₃), and acids (trifluoroacetic acid, triflic acid) were examined under our optimized conditions (Table 1, entries 9–12, 16–17, 26–27). However, no improvement in the yield of product 3aa was found. During the optimization process, different wavelengths of the light source, ranging from 360 to 455 nm, were tested. The results indicated that the wavelength (420–425 nm) was the most effective light source for the reaction (Table 1, entries 18–22). To further improve the yield of 3aa, degassed hexafluoroisopropanol (HFIP) was added as cosolvent. Pleasingly, the solvent mixture of MeCN and HFIP (V_MeCN:V_HFIP = 3:1) led to the highest yield of 3aa at 71% (Table 1, entries 23–25). This improvement could be attributed to the previously reported role of HFIP as a radical stabilizer.²³ Optimizing the reaction conditions revealed that the optimal reaction time is 10 h, as indicated in Table 1 (Table 1, entries 24, 28, and 29). Interestingly, extending the reaction time beyond 10 to 16 h did not result in an improvement in the yield of 3aa.

With the optimized reaction condition in hand, the applicability of the synthetic approach to a range of functionalized 2H-indazoles was explored (Figure 2). The functional group tolerance of 2H-indazoles at C-5 and C-6 position was also examined. The introduction of both halogen atoms (−F, −Cl, −Br) (3ba–3da) or electron-donating groups (−OMe, −Me, −OMeO−) (3ea–3ha) at the C-5 and C-6 position of 2H-indazoles resulted in the target products with the yields ranging from 48 to 64%. The synthesis of product 3ia showcased the feasibility of conducting the synthesis using 2H-indazoles containing multiple functional groups on various sites. Various indazoles bearing aromatic rings that were functionalized with diverse functional groups (e.g., −Me, −OMe, −SMe, −F, −Cl, −Br, −CF₃, −COOEt, −phenyl) along with heteroaryl substituents (e.g., pyridyl) at the 2N position were effectively converted into their corresponding 3-acyl-2H-indazoles in fair to good yields (3ja–3za, 33–78%). It was noted that substrates with ortho-methyl substituted phenyl groups at 2N position led to lower yields of the products (e.g., 3qa) compared to the products with meta- and para-substituted phenyl groups (e.g., 3oa, 3pa). This suggested that steric hindrance at the ortho position affected the reaction efficiency. Additionally, when aromatic functional group at 2N position was switched to aliphatic substituent, as in the case of 2-(cyclohexyl)-2H-indazole (1w), a poor isolated yield of 3wa was obtained (25%), even after extending the reaction time to 20 h. It was proposed that the broader light absorption range of C3-acylated 2H-indazole products (e.g., 3aa and 3wa) could inhibit the continuous formation of desired product (for the product inhabitation effect and UV–vis spectrum, see Figures S2–S4 in Supporting Information).

Figure 2.

Substrate scope for the synthesis of 3-acyl-2H-indazoles.

After the exploration of the scope of 2H-indazole derivatives, a variety of aryl and hetaryl α-keto acids were synthesized (see Experimental Section). These α-keto acids were then investigated for the photoinitiated decarboxylative radical acylation reaction with 1a. It was found that our reaction system exhibited versatility and accommodated a wide range of α-keto acids, allowing them to smoothly undergo the acylation process and yield the desired acylated 2H-indazole derivatives (3ab–3ak) with moderate to good yields. Aromatic α-keto acids bearing electron-withdrawing groups (e.g., −F, −Cl, −Br, −CF₃) at the ortho- and para-positions of the aromatic rings provided the desired products (e.g., 3ab–3af) with yields ranging from 52 to 76%. Moreover, α-keto acids with electron-donating groups (−OMe, −Me, −OMeO−) were also effective acylating reagents, although they resulted in slightly lower yields (40–59%) of acylated 2H-indazoles (3ag–3aj). Pleasingly, a good yield (62%) of 3ak was obtained when naphthyl α-keto acid (2k) was used. Unfortunately, aliphatic α-keto acids, such as 2-oxopropanoic acid (2l), could not lead to the desired products 3al using our method. To further establish the scalability of our method, we performed large-scale reactions using different quantities of 1a as starting materials, ranging from 3 (0.58 g) to 6 mmol (1.17 g). The isolated yields of 3aa were 64 and 56%, respectively (for details, please refer to the SI).

To gain preliminary insight into the reaction mechanism, a series of control experiments were conducted. When the free radical inhibitor TEMPO (2,2,6,6-tetramethylpiperidinooxyl) was introduced (Figure 3a), the transformation was completely suppressed. The HRMS analysis of the reaction mixture confirmed the formation of acyl radical during the photoreaction, as evidenced by the detection of compound 4, an adduct of TEMPO and acyl radical ([M + H]⁺ found 262.1800, calculated 262.1802, detailed HRMS see Figure S1). This finding strongly suggested that the reaction likely proceeded through a free radical pathway.

Figure 3.

Control experiments.

As depicted in Figure 3b, when the light source was removed from the reaction, product 3aa was not detected, confirming that the reaction was indeed light driven. Interestingly, when the reaction was conducted in an air atmosphere, the reaction was quenched and did not proceed. This observation diverged from a method developed by He and co-workers,²⁴ where oxygen played a crucial role in visible-light-induced aerobic acylation of quinoxalin-2(1H)-ones with α-keto acids. In this process, an acyl radical and byproduct H₂O₂ were generated through a hydrogen-atom-transfer (HAT) process via excited-state singlet oxygen (¹O₂). Jin and co-workers reported the generation of hydrogen gas during the synthesis of quinazolinone derivative under photoinduced conditions using α-keto acids.²⁵ To investigate the possibility of formation of hydrogen gas from the H• radical, the gas mixture from the headspace of the reaction mixture was analyzed by GC with a TCD detector (Figure S7). However, only the formation of CO₂ and minor CO were confirmed, and no hydrogen gas was generated in our system. In addition, we carried out fluorescence quenching experiments involving 1a and 2a. Upon the addition of 2a to the visible light irradiated 1a, the fluorescence intensity of 1a decreased (Figure 3c, see SI for a detailed procedure). The straight Stern–Volmer plot of the quenching experiment in Figure 3c indicated that the excited state of 1a could be quenched by 2a. Further fluorescence quenching study demonstrated that no energy transfer between 3aa and 2a (Figure S6 in Supporting Information). Moreover, GC-MS analysis of reaction mixture at 10 h (reaction condition as listed in entry 24, Table 1) revealed the generation of byproducts such as benzaldehyde, benzoic acid and benzil during the reaction (Figure 4a). This was consistent with previous reports that under light irradiation, α-keto acids could undergo a complex decomposition mechanism and form a variety of radicals and organic intermediates.²⁴⁻²⁶

Based on the above obtained results and relevant literature studies,^26,27,28 a plausible reaction mechanism was proposed (Figure 4b). Initially, 1a absorbs visible light, transitioning to an exciting state (1a*). Subsequently, the ground state 2a undergoes energy transfer from 1a*, leading to the excited state 2a*, which could homolyze to form an acyl radical (A) and carboxyl radical (B).^26,27

The acyl radical (A) could then form benzil (C) or further decompose to CO and phenyl radical (Ph•), with the later react with B to form benzoic acid (D). In the meantime, B could react with another B to form CO₂ and formic acid (E).²⁶ The generated acyl radical A could attack the C-3 position of 1a, forming radical intermediate F. Finally, the extraction of H• from intermediate F took place with radical R• (e.g., A, B, or other radicals generated during the decomposition of α-keto acids), leading to the formation of the final target product 3aa.

Conclusions

In conclusion, we have presented a novel and efficient method for visible-light-induced synthesis of functionalized 3-acyl-2H-indazoles. Notably, the utilization of a self-catalyzed energy transfer process between 2H-indazoles and α-keto acids offered this method several advantages, induced organic synthesis without photocatalyst conditions. This method demonstrated a broad substrate scope and operational simplicity under mild conditions. Further investigation on visible-light-induced organic synthesis under without photocatalyst conditions is currently underway in our laboratory.

Experimental Section

General Information

¹H NMR spectra and ¹³C NMR spectra were recorded on a Bruker AVANCE NEO (400 MHz/500 MHz/600 MHz) spectrometer and Bruker AVANCE NEO (100 MHz/125 MHz/150 MHz) spectrometer at 25 °C, respectively. High resolution mass spectra (HRMS) were measured with an Agilent 6230 TOF instrument.

Safety Statement

Caution! Aldehydes and anilines have irritating odors, and inhalation can cause damage to the body. Therefore, weighing and transferring these chemicals should be carried out within a fume hood. Additionally, exposure to light sources can be harmful to the eyes, necessitating the use of protective goggles.

General Procedure for the Synthesis of Functionalized 3-Acyl-2H-indazoles

In a clean Schlenk flask, 2H-indazoles (0.2 mmol) and α-keto acids (5 equiv., 1.0 mmol) were placed. The Schlenk flask was evacuated and purged with nitrogen three times using a Schlenk line. Subsequently, 3 mL of degassed MeCN and 1 mL of degassed HFIP were added under nitrogen charging conditions, and the flask was tightly sealed. The reaction was conducted under 420–425 nm light for 10–20 h. After completion of the reaction, the solution was concentrated, and flash chromatography was performed using petroleum ether (PE)/ethyl acetate (EA) = 100:1–15:1 as eluent.

Phenyl(2-phenyl-2H-indazol-3-yl)methanone (3aa)¹⁷

The product 3aa was prepared by the general procedure with 1a (38.8 mg, 0.2 mmol). 41.7 mg (70%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.91–7.86 (m, 3H), 7.62–7.58 (m, 1H), 7.56–7.53 (m, 2H), 7.48–7.37 (m, 7H), 7.20–7.17 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.1, 148.7, 140.6, 137.9, 133.7, 132.4, 130.0, 129.2, 129.0, 128.8, 127.1, 125.7, 125.1, 124.2, 120.7, 118.7.

(5-Fluoro-2-phenyl-2H-indazol-3-yl)(phenyl)methanone (3ba)¹⁷

The product 3ba was prepared by the general procedure with 1b (42.5 mg, 0.2 mmol). 36.8 mg (59%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.89–7.83 (m, 3H), 7.63–7.59 (m, 1H), 7.54–7.40 (m, 7H), 7.19 (td, J₁ = 9.1 Hz, J₂ = 2.4 Hz, 1H), 6.95 (dd, J₁ = 9.2 Hz, J₂ = 2.4 Hz, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.7, 160.4 (d, J = 243.4 Hz), 146.0, 140.5, 137.6, 133.8, 132.7 (d, J = 8.4 Hz), 129.9, 129.22, 129.17, 128.9, 125.5, 124.1 (d, J = 12.0 Hz), 120.9 (d, J = 9.9 Hz), 118.8 (d, J = 28.7 Hz), 103.7 (d, J = 25.5 Hz).

(5-Chloro-2-phenyl-2H-indazol-3-yl)(phenyl)methanone (3ca)

The product 3ca was prepared by the general procedure with 1c (45.8 mg, 0.2 mmol). 32.3 mg (49%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.85–7.82 (m, 3H), 7.64–7.60 (m, 1H), 7.53–7.38 (m, 8H), 7.34–7.31 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.7, 147.0, 140.3, 137.5, 134.0, 132.1, 131.1, 130.0, 129.3 (3C), 128.9, 128.7, 125.5, 124.5, 120.2, 119.5. HRMS (ESI): m/z calcd for C₂₀H₁₄ClN₂O [M + H]⁺ 333.0789 Found 333.0792.

(5-Bromo-2-phenyl-2H-indazol-3-yl)(phenyl)methanone (3da)²⁹

The product 3da was prepared by the general procedure with 1d (54.7 mg, 0.2 mmol). 34.1 mg (46%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.85–7.82 (m, 2H), 7.77 (d, J = 9.1 Hz, 1H), 7.64–7.58 (m, 2H), 7.53–7.39 (m, 8H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.8, 147.1, 140.3, 137.5, 134.0, 131.9, 131.1, 130.0, 129.3, 128.9, 125.5, 125.2, 122.9, 120.3, 119.2.

(5-Methoxy-2-phenyl-2H-indazol-3-yl)(phenyl)methanone (3ea)

The product 3ea was prepared by the general procedure with 1e (44.9 mg, 0.2 mmol). 31.0 mg (48%); yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 7.83–7.80 (m, 2H), 7.77 (d, J = 9.0 Hz, 1H), 7.57–7.53 (m, 1H), 7.51–7.48 (m, 2H), 7.43–7.32 (m, 5H), 7.07 (dd, J₁ = 9.3 Hz, J₂ = 2.4 Hz, 1H), 6.64 (d, J = 2.4 Hz, 1H), 3.69 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.2, 157.8, 145.6, 140.7, 138.1, 133.3, 131.6, 129.8, 129.1, 128.7, 128.6, 125.5, 125.4, 122.3, 120.0, 97.1, 55.4. HRMS (ESI): m/z calcd for C₂₁H₁₇N₂O₂ [M + H]⁺ 329.1285 Found 329.1283.

(6-Chloro-2-phenyl-2H-indazol-3-yl)(phenyl)methanone (3fa)

The product 3fa was prepared by the general procedure with 1f (45.8 mg, 0.2 mmol). 35.6 mg (54%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.87–7.83 (m, 3H), 7.61 (t, J = 7.4 Hz, 1H), 7.53–7.40 (m, 7H), 7.32 (d, J = 9.0 Hz, 1H), 7.13 (d, J = 9.0 Hz, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.9, 148.8, 140.3, 137.6, 134.0, 133.2, 132.8, 130.0, 129.3 (3C), 128.9, 126.5, 125.6, 122.5, 122.0, 117.5. HRMS (ESI): m/z calcd for C₂₀H₁₄ClN₂O [M + H]⁺ 333.0789 Found 333.0792.

(6-Methyl-2-phenyl-2H-indazol-3-yl)(phenyl)methanone (3ga)¹⁷

The product 3ga was prepared by the general procedure with 1g (41.7 mg, 0.2 mmol). 39.7 mg (64%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.91–7.88 (m, 2H), 7.66–7.60 (m, 2H), 7.57–7.54 (m, 2H), 7.50–7.41 (m, 5H), 7.27 (d, J = 7.8 Hz, 1H), 7.05 (dd, J₁ = 8.8 Hz, J₂ = 1.5 Hz, 1H), 2.51 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.0, 149.2, 140.6, 137.9, 137.1, 133.5, 132.1, 129.9, 129.1, 128.8, 128.6, 128.0, 125.5, 122.6, 120.1, 116.8, 22.1.

Phenyl(2-phenyl-2H-[1,3]dioxolo[4,5-f]indazol-3-yl)methanone (3ha)¹⁷

The product 3ha was prepared by the general procedure with 1h (47.7 mg, 0.2 mmol). 42.7 mg (63%); yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 7.84–7.81 (m, 2H), 7.60–7.55 (m, 1H), 7.48–7.42 (m, 4H), 7.41–7.33 (m, 3H), 7.11 (s, 1H), 6.60 (s, 1H), 6.00 (s, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.2, 149.8, 148.2, 146.3, 140.6, 137.9, 133.5, 132.1, 129.9, 129.1, 128.8, 128.5, 125.3, 121.2, 101.6, 95.8, 94.7.

(5-Fluoro-2-(p-tolyl)-2H-indazol-3-yl)(phenyl)methanone (3ia)

The product 3ia was prepared by the general procedure with 1i (45.3 mg, 0.2 mmol). 42.6 mg (65%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.88–7.84 (m, 3H), 7.65–7.60 (m, 1H), 7.48 (t, J = 7.9 Hz, 2H), 7.42–7.38 (m, 2H), 7.22 (d, J = 8.2 Hz, 2H), 7.17 (td, J₁ = 9.2 Hz, J₂ = 2.4 Hz, 1H), 6.92 (dd, J₁ = 9.2 Hz, J₂ = 2.4 Hz, 1H), 2.38 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.8, 160.7 (d, J = 243.1 Hz), 145.9, 139.3, 138.1, 137.7, 133.8, 132.6 (d, J = 8.3 Hz), 129.9, 129.8, 128.9, 125.3, 124.0 (d, J = 12.0 Hz), 120.9 (d, J = 10.0 Hz), 118.7 (d, J = 28.8 Hz), 103.7 (d, J = 25.4 Hz), 21.3. HRMS (ESI): m/z calcd for C₂₁H₁₆FN₂O [M + H]⁺ 331.1241. Found 331.1240.

(2-(4-Fluorophenyl)-2H-indazol-3-yl)(phenyl)methanone (3ja)

The product 3ja was prepared by the general procedure with 1j (42.5 mg, 0.2 mmol). 36.3 mg (58%); white solid; ¹H NMR (400 MHz, (CD₃)₂SO): δ 7.05 (d, J = 8.8 Hz, 1H), 6.98–6.95 (m, 2H), 6.86–6.78 (m, 3H), 6.68 (t, J = 7.8 Hz, 2H), 6.60–6.56 (m, 1H), 6.50–6.44 (m, 2H), 6.39–6.38 (m, 2H); ¹³C {¹H} NMR (100 MHz, (CD₃)₂SO): δ 185.4, 161.9 (d, J = 245.0 Hz), 147.8, 137.5, 136.7 (d, J = 3.1 Hz), 133.7, 132.2, 129.6, 128.8, 127.9 (d, J = 9.0 Hz), 127.2, 125.3, 123.5, 120.2, 118.3, 116.0 (d, J = 23.1 Hz). HRMS (ESI): m/z calcd for C₂₀H₁₄FN₂O [M + H]⁺ 317.1085. Found 317.1090.

(2-(3-Fluorophenyl)-2H-indazol-3-yl)(phenyl)methanone (3ka)

The product 3ka was prepared by the general procedure with 1k (42.5 mg, 0.2 mmol). 33.0 mg (52%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.87 (m, 3H), 7.64 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.7 Hz, 2H), 7.41–7.29 (m, 5H), 7.20–7.17 (m, 1H), 7.15–7.10 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.8, 162.6 (d, J = 246.9 Hz), 148.7, 141.7 (d, J = 10.0 Hz), 137.7, 133.8, 132.4, 130.3 (d, J = 8.9 Hz), 129.9, 128.8, 127.4, 125.4, 124.1, 121.4 (d, J = 3.3 Hz), 120.6, 118.6, 116.0 (d, J = 21.0 Hz), 113.3 (d, J = 25.0 Hz). HRMS (ESI): m/z calcd for C₂₀H₁₄FN₂O [M + H]⁺ 317.1085. Found 317.1083.

(2-(4-Chlorophenyl)-2H-indazol-3-yl)(phenyl)methanone (3la)¹⁸

The product 3la was prepared by the general procedure with 1l (45.8 mg, 0.2 mmol). 30.2 mg (46%); white solid; ¹H NMR (400 MHz, (CD₃)₂SO): δ 7.91 (d, J = 8.8 Hz, 1H), 7.86–7.84 (m, 2H), 7.74–7.70 (m, 1H), 7.66–7.62 (m, 2H), 7.58–7.54 (m, 4H), 7.47–7.43 (m, 1H), 7.27–7.20 (m, 2H); ¹³C {¹H} NMR (100 MHz, (CD₃)₂SO): δ 185.4, 148.0, 139.1, 137.4, 133.8, 133.6, 132.1, 129.6, 129.1, 128.8, 127.4, 127.3, 125.4, 123.5, 120.2, 118.4.

(2-(4-Bromophenyl)-2H-indazol-3-yl)(phenyl)methanone (3ma)¹⁷

The product 3ma was prepared by the general procedure with 1m (54.7 mg, 0.2 mmol). 30.2 mg (40%); white solid; ¹H NMR (400 MHz, (CD₃)₂SO): δ 7.91 (d, J = 8.8 Hz, 1H), 7.86–7.84 (m, 2H), 7.74–7.68 (m, 3H), 7.58–7.53 (m, 4H), 7.46–7.42 (m, 1H), 7.26–7.19 (m, 2H); ¹³C {¹H} NMR (100 MHz, (CD₃)₂SO): δ 185.4, 148.0, 139.5, 137.4, 133.9, 132.10, 132.07, 129.6, 128.8, 127.7, 127.3, 125.4, 123.5, 122.1, 120.2, 118.4.

Phenyl(2-(4-(trifluoromethyl)phenyl)-2H-indazol-3-yl)methanone (3na)¹⁷

The product 3na was prepared by the general procedure with 1n (52.4 mg, 0.2 mmol). 51.6 mg (71%); White solid; ¹H NMR (400 MHz, CDCl₃): δ 7.94–7.87 (m, 3H), 7.73–7.65 (m, 5H), 7.54–7.49 (m, 2H), 7.43–7.38 (m, 1H), 7.33–7.31 (m, 1H), 7.22–7.18 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.8, 149.0, 143.4, 137.7, 134.1, 132.5, 131.0 (q, J = 32.9 Hz), 130.1, 129.0, 127.6, 126.4 (q, J = 3.7 Hz), 126.1, 125.7, 124.3, 123.8 (d, J = 270.6 Hz), 120.7, 118.8.

Phenyl(2-(p-tolyl)-2H-indazol-3-yl)methanone (3oa)¹⁷

The product 3oa was prepared by the general procedure with 1o (41.7 mg, 0.2 mmol). 37.5 mg (60%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.87 (m, 3H), 7.64–7.60 (m, 1H), 7.50–7.46 (m, 2H), 7.44–7.41 (m, 2H), 7.39–7.36 (m, 1H), 7.35–7.33 (m, 1H), 7.23 (d, J = 8.2 Hz, 2H), 7.19–7.15 (m, 1H), 2.39 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.1, 148.6, 139.2, 138.2, 138.0, 133.7, 132.3, 130.1, 129.8, 128.8, 127.0, 125.4, 125.0, 124.1, 120.7, 118.6, 21.3.

Phenyl(2-(m-tolyl)-2H-indazol-3-yl)methanone (3pa)³⁰

The product 3pa was prepared by the general procedure with 1p (41.7 mg, 0.2 mmol). 40.6 mg (65%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.86 (m, 3H), 7.63–7.59 (m, 1H), 7.49–7.44 (m, 2H), 7.40–7.37 (m, 3H), 7.29–7.27 (m, 2H), 7.23–7.16 (m, 2H), 2.38 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.2, 148.6, 140.5, 139.4, 138.0, 133.7, 132.4, 130.0, 129.9, 129.0, 128.7, 127.1, 126.2, 125.1, 124.2, 122.8, 120.7, 118.6, 21.4.

Phenyl(2-(o-tolyl)-2H-indazol-3-yl)methanone (3qa)

The product 3qa was prepared by the general procedure with 1q (41.7 mg, 0.2 mmol). 20.6 mg (33%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.91–7.85 (m, 3H), 7.65–7.61 (m, 1H), 7.49 (t, J = 7.6 Hz, 2H), 7.42–7.29 (m, 6H), 7.22–7.18 (m, 1H), 2.12 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.3, 148.5, 140.2, 138.1, 134.8, 133.5, 133.4, 130.9, 129.9, 129.7, 128.7, 127.2, 126.9, 126.5, 125.1, 123.0, 120.9, 118.8, 17.7. HRMS (ESI): m/z calcd for C₂₁H₁₇N₂O [M + H]⁺ 313.1335. Found 313.1334.

(2-(4-Methoxyphenyl)-2H-indazol-3-yl)(phenyl)methanone (3ra)¹⁷

The product 3ra was prepared by the general procedure with 1r (44.9 mg, 0.2 mmol). 26.8 mg (41%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.89–7.86 (m, 3H), 7.61 (t, J = 7.5 Hz, 1H), 7.49–7.45 (m, 4H), 7.40–7.33 (m, 2H), 7.19–7.15 (m, 1H), 6.95–6.91 (m, 2H), 3.82 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.2, 160.0, 148.5, 138.0, 133.8, 133.7, 132.2, 130.1, 128.8, 127.0, 126.8, 125.0, 124.1, 120.7, 118.5, 114.4, 55.7.

(2-(4-(tert-Butyl)phenyl)-2H-indazol-3-yl)(phenyl)methanone (3sa)

The product 3sa was prepared by the general procedure with 1s (50.1 mg, 0.2 mmol). 49.2 mg (70%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.86 (m, 3H), 7.62–7.58 (m, 1H), 7.48–7.35 (m, 8H), 7.20–7.16 (m, 1H), 1.32 (s, 9H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.2, 152.2, 148.6, 138.1, 133.6, 132.2, 131.3, 130.0, 128.7, 127.0, 126.2, 125.2, 125.1, 124.2, 120.7, 118.6, 34.9, 31.4. HRMS (ESI): m/z calcd for C₂₄H₂₃N₂O [M + H]⁺ 355.1805. Found 355.1805.

(2-(4-(Methylthio)phenyl)-2H-indazol-3-yl)(phenyl)methanone (3ta)

The product 3ta was prepared by the general procedure with 1t (48.1 mg, 0.2 mmol). 23.9 mg (35%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.87 (m, 3H), 7.63 (t, J = 7.5 Hz, 1H), 7.52–7.44 (m, 4H), 7.40–7.36 (m, 1H), 7.32 (d, J = 8.5 Hz, 1H), 7.29–7.27 (m, 2H), 7.19–7.15 (m, 1H), 2.49 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.0, 148.5, 140.2, 137.8, 137.5, 133.7, 132.1, 130.0, 128.7, 127.1, 126.6, 125.8, 125.1, 124.1, 120.6, 118.5, 15.7. HRMS (ESI): m/z calcd for C₂₁H₁₇N₂OS [M + H]⁺ 345.1056. Found 345.1057.

Ethyl 4-(3-Benzoyl-2H-indazol-2-yl)benzoate (3ua)

The product 3ua was prepared by the general procedure with 1u (53.3 mg, 0.2 mmol). 57.8 mg (78%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 8.14–8.11 (m, 2H), 7.92–7.87 (m, 3H), 7.66–7.61 (m, 3H), 7.49 (t, J = 7.9 Hz, 2H), 7.41–7.37 (m, 1H), 7.34 (d, J = 8.6 Hz, 1H), 7.20–7.16 (m, 1H), 4.39 (q, J = 7.1 Hz, 2H), 1.40 (t, J = 7.1 Hz, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.9, 165.7, 149.0, 143.9, 137.7, 134.0, 132.5, 130.8, 130.6, 130.1, 128.9, 127.5, 125.50, 125.45, 124.3, 120.7, 118.7, 61.4, 14.4. HRMS (ESI): m/z calcd for C₂₃H₁₉N₂O₃ [M + H]⁺ 371.1390. Found 371.1389.

Phenyl(2-(pyridin-2-yl)-2H-indazol-3-yl)methanone (3va)¹⁸

The product 3va was prepared by the general procedure with 1v (39.1 mg, 0.2 mmol). 27.7 mg (47%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 8.22–8.20 (m, 1H), 8.05 (d, J = 8.2 Hz,1H), 7.89–7.83 (m, 4H), 7.57–7.52 (m, 1H), 7.49–7.47 (m, 1H), 7.44–7.36 (m, 3H), 7.23–7.19 (m, 1H), 7.18–7.14 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): 187.1, 151.8, 149.1, 148.0, 138.7, 138.0, 133.2, 132.5, 129.5, 128.6, 127.8, 124.7, 123.7, 123.3, 120.6, 118.4, 117.3.

(2-Cyclohexyl-2H-indazol-3-yl)(phenyl)methanone (3wa)¹⁷

The product 3wa was prepared by the general procedure with 1w (40.1 mg, 0.2 mmol). 14.1 mg (25%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90–7.85 (m, 3H), 7.67 (t, J = 7.5 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 7.30 (t, J = 7.4 Hz, 1H), 7.07 (t, J = 6.7 Hz, 1H), 7.02–7.00 (m, 1H), 5.23–5.15 (m, 1H), 2.25–2.15 (m, 4H), 2.00–1.95 (m, 2H), 1.81–1.77 (m, 1H), 1.58–1.47 (m, 2H), 1.44–1.36 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): 186.6, 147.4, 139.0, 133.3, 131.0, 129.9, 128.7, 125.8, 124.4, 123.5, 120.6, 118.4, 61.5, 33.9, 25.8, 25.4.

(2-(3,5-Dimethylphenyl)-2H-indazol-3-yl)(phenyl)methanone (3xa)¹⁷

The product 3xa was prepared by the general procedure with 1x (44.5 mg, 0.2 mmol). 41.7 mg (64%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.92–7.86 (m, 3H), 7.64–7.60 (m, 1H), 7.50–7.45 (m, 2H), 7.42–7.38 (m, 2H), 7.22–7.18 (m, 1H), 7.16 (s, 2H), 7.03 (s, 1H), 2.33 (s, 6H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.1, 148.4, 140.4, 139.0, 138.0, 133.5, 132.2, 130.7, 129.8, 128.6, 126.9, 125.0, 124.1, 123.3, 120.6, 118.5, 21.2.

(2-(3-Chloro-4-methylphenyl)-2H-indazol-3-yl)(phenyl)methanone (3ya)

The product 3ya was prepared by the general procedure with 1y (48.6 mg, 0.2 mmol). 51.9 mg (75%); yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 7.88 (t, J = 7.3 Hz, 3H), 7.66–7.61 (m, 2H), 7.49 (t, J = 7.8 Hz, 2H), 7.38 (t, J = 8.8 Hz, 1H), 7.33–7.25 (m, 3H), 7.17 (t, J = 7.6 Hz, 1H), 2.40 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.9, 148.7, 139.2, 137.9, 137.2, 134.8, 133.8, 132.3, 131.1, 130.0, 128.8, 127.3, 126.2, 125.3, 124.1, 123.8, 120.7, 118.7, 20.0. HRMS (ESI): m/z calcd for C₂₁H₁₆ClN₂O [M + H]⁺ 347.0946. Found 347.0946.

(2-(3,4-Dichlorophenyl)-2H-indazol-3-yl)(phenyl)methanone (3za)

The product 3za was prepared by the general procedure with 1z (52.7 mg, 0.2 mmol). 55.3 mg (75%); yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 7.91–7.85 (m, 3H), 7.74 (d, J = 2.5 Hz, 1H), 7.69–7.64 (m, 1H), 7.53–7.48 (m, 3H), 7.41–7.35 (m, 2H), 7.30 (d, J = 8.6 Hz, 1H), 7.20–7.16 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.6, 148.8, 139.7, 137.6, 134.0, 133.3, 133.2, 132.3, 130.6, 130.0, 128.9, 127.54, 127.47, 125.6, 124.8, 124.1, 120.6, 118.6. HRMS (ESI): m/z calcd for C₂₀H₁₃Cl₂N₂O [M + H]⁺ 367.0399. Found 367.0403.

(4-Fluorophenyl)(2-phenyl-2H-indazol-3-yl)methanone (3ab)¹⁹

The product 3ab was prepared by the general procedure with 2b (168.2 mg, 1 mmol). 48.4 mg (76%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.92–7.89 (m, 3H), 7.54–7.52 (m, 2H), 7.46–7.38 (m, 5H), 7.23–7.19 (m, 1H), 7.15–7.11 (m, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 184.6, 166.1 (d, J = 254.6 Hz), 148.7, 140.5, 134.2 (d, J = 2.9 Hz), 132.7 (d, J = 9.4 Hz), 132.1, 129.3, 129.2, 127.3, 125.6, 125.3, 124.1, 120.5, 118.8, 116.1 (d, J = 22.0 Hz).

(4-Chlorophenyl)(2-phenyl-2H-indazol-3-yl)methanone (3ac)¹⁷

The product 3ac was prepared by the general procedure with 2c (184.6 mg, 1 mmol). 46.2 mg (69%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.89 (d, J = 8.8 Hz, 1H), 7.83–7.80 (m, 2H), 7.53–7.51 (m, 2H), 7.47–7.38 (m, 7H), 7.24–7.20 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 184.8, 148.7, 140.5, 140.2, 136.2, 132.0, 131.4, 129.3, 129.24, 129.17, 127.3, 125.7, 125.5, 124.2, 120.5, 118.8.

(4-Bromophenyl)(2-phenyl-2H-indazol-3-yl)methanone (3ad)¹⁷

The product 3ad was prepared by the general procedure with 2d (229.1 mg, 1 mmol). 41.8 mg (56%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90 (d, J = 8.7 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.4 Hz, 2H), 7.53–7.50 (m, 2H), 7.47–7.37 (m, 5H), 7.22 (t, J = 6.6 Hz, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 184.9, 148.7, 140.5, 136.6, 132.1, 131.9, 131.5, 129.3, 129.2, 128.9, 127.3, 125.6, 125.5, 124.2, 120.5, 118.8.

(2-Fluorophenyl)(2-phenyl-2H-indazol-3-yl)methanone (3ae)¹⁷

The product 3ae was prepared by the general procedure with 2e (168.2 mg, 1 mmol). 42.9 mg (68%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.90 (d, J = 8.8 Hz, 1H), 7.59 (td, J₁ = 7.4 Hz, J₂ = 1.8 Hz, 1H), 7.53–7.50 (m, 2H), 7.48–7.36 (m, 6H), 7.26–7.23 (m, 1H), 7.20 (td, J₁ = 7.5 Hz, J₂ = 1.0 Hz, 1H), 7.00–6.95 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 182.0, 160.3 (d, J = 252.6 Hz), 148.7, 140.3, 134.3 (d, J = 8.5 Hz), 133.0, 130.7 (d, J = 2.1 Hz), 129.2, 129.0, 127.6 (d, J = 12.7 Hz), 127.3, 126.1, 126.0, 124.6 (d, J = 3.6 Hz), 124.4, 120.4, 118.8, 116.4 (d, J = 21.4 Hz).

(2-Phenyl-2H-indazol-3-yl)(2-(trifluoromethyl)phenyl)methanone (3af)¹⁷

The product 3af was prepared by the general procedure with 2f (218.2 mg, 1 mmol). 37.9 mg (52%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.89 (d, J = 8.7 Hz, 1H), 7.79 (d, J = 6.6 Hz, 1H), 7.65–7.52 (m, 4H), 7.46–7.44 (m, 4H), 7.40–7.36 (m, 1H), 7.19–7.15 (m, 1H), 6.85 (d, J = 8.7 Hz, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 183.3, 148.6, 140.7, 138.4, 131.9, 131.5, 130.8, 129.4, 129.0 (2C), 128.8, 128.1 (q, J = 32.0 Hz), 127.1 (q, J = 4.1 Hz), 126.3, 126.1, 125.0, 123.5 (q, J = 272.0 Hz), 120.2, 119.0.

(2-Phenyl-2H-indazol-3-yl)(p-tolyl)methanone (3ag)¹⁷

The product 3ag was prepared by the general procedure with 2g (164.2 mg, 1 mmol). 36.7 mg (59%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.91 (d, J = 8.9 Hz, 1H), 7.83 (d, J = 8.1 Hz, 2H), 7.59–7.56 (m, 2H), 7.48–7.39 (m, 5H), 7.29 (d, J = 8.0 Hz, 2H), 7.19 (t, J = 8.6 Hz, 1H), 2.47 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.8, 148.6, 144.9, 140.6, 135.3, 132.6, 130.3, 129.5, 129.2, 129.0, 127.1, 125.6, 124.9, 124.0, 120.8, 118.6, 21.9.

(2-Phenyl-2H-indazol-3-yl)(m-tolyl)methanone (3ah)¹⁷

The product 3ah was prepared by the general procedure with 2h (164.2 mg, 1 mmol). 36.0 mg (58%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.91–7.88 (m, 1H), 7.69–7.67 (m, 2H), 7.56–7.53 (m, 2H), 7.45–7.33 (m, 7H), 7.20–7.17 (m, 1H), 2.37 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.3, 148.7, 140.6, 138.7, 137.9, 134.5, 132.6, 130.5, 129.2, 129.0, 128.6, 127.4, 127.1, 125.6, 125.1, 124.2, 120.8, 118.6, 21.4.

(3-Methoxyphenyl)(2-phenyl-2H-indazol-3-yl)methanone (3ai)¹⁷

The product 3ai was prepared by the general procedure with 2i (180.2 mg, 1 mmol). 26.1 mg (40%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.89 (d, J = 8.6 Hz, 1H), 7.56–7.54 (m, 2H), 7.47–7.34 (m, 8H), 7.21–7.14 (m, 2H), 3.82 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.8, 159.9, 148.7, 140.6, 139.2, 132.4, 129.8, 129.2, 129.1, 127.2, 125.6, 125.2, 124.2, 123.0, 120.8, 120.6, 118.6, 113.7, 55.6.

Benzo[d][1,3]dioxol-5-yl(2-phenyl-2H-indazol-3-yl)methanone (3aj)¹⁷

The product 3aj was prepared by the general procedure with 2j (194.2 mg, 1 mmol). 33.7 mg (50%); white solid; ¹H NMR (400 MHz, CDCl₃): δ 7.87 (d, J = 8.7 Hz, 1H), 7.56–7.52 (m, 2H), 7.50–7.47 (m, 1H), 7.46–7.36 (m, 6H), 7.19 (t, J = 7.8 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 6.07 (s, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 184.4, 152.6, 148.5, 148.4, 140.5, 132.4, 132.3, 129.2, 128.9, 127.4, 127.0, 125.4, 124.8, 123.8, 120.6, 118.5, 109.3, 108.1, 102.1.

Naphthalen-2-yl(2-phenyl-2H-indazol-3-yl)methanone (3ak)¹⁷

The product 3ak was prepared by the general procedure with 2k (200.2 mg, 1 mmol). 43.1 mg (62%); yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 8.41 (s, 1H), 8.01–7.99 (m, 1H), 7.95–7.87 (m, 4H), 7.66–7.54 (m, 4H), 7.45–7.36 (m, 5H), 7.18–7.14 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.9, 148.6, 140.6, 135.9, 135.1, 132.52, 132.48, 132.4, 129.7, 129.2, 129.0, 128.9, 128.8, 127.9, 127.11, 127.08, 125.5, 125.1, 125.0, 124.1, 120.6, 118.6.

General Procedure for the synthesis of 2H-indazoles³¹

Aryl aldehyde (52.5 mmol), aniline (1.2 equiv., 63 mmol), sodium azide (2 equiv., 6.83 g, 105 mmol), cuprous iodide (10 mol %, 1.00 g, 5.25 mmol), tetramethylethylenediamine (10 mol %, 0.61 g, 5.25 mmol), and DMSO (120 mL) were added to a clean round-bottom flask. Then, the reaction mixture was heated to 120 °C (the heat source is an oil bath) for 24 h. After cooling to room temperature, diatomaceous earth was used for the filtration of the reaction mixture. The filter cake was washed with ethyl acetate, and the organic phase was combined and extracted with saturated saline solution. Then, the upper organic phase was collected, dried with anhydrous NaSO₄, and filtered. Then, the organic phase was concentrated, followed by flash chromatography using EA and PE as eluents. The obtained product from column chromatography were collected and further recrystallized using PE/EA. Then, the solid were filtered, washed with PE, and dried under high-vacuum to obtain 2H-indazoles.

2-Phenyl-2H-indazole (1a)³¹

1a was prepared by the general procedure. White solid; ¹H NMR (600 MHz, CDCl₃): δ 8.39 (s, 1H), 7.91–7.89 (m, 2H), 7.83–7.81 (m, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.53–7.50 (m, 2H), 7.41–7.38 (m, 1H), 7.35–7.32 (m, 1H), 7.14–7.11 (m, 1H); ¹³C {¹H} NMR (150 MHz, CDCl₃): δ 149.9, 140.6, 129.7, 128.0, 126.9, 122.9, 122.6, 121.1, 120.5 (2C), 118.0.

5-Fluoro-2-phenyl-2H-indazole (1b)¹⁷

1b was prepared by the general procedure with 2-bromo-5-fluorobenzaldehyde. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.34 (s, 1H), 7.88–7.86 (m, 2H), 7.78–7.75 (m, 1H), 7.53–7.50 (m, 2H), 7.42–7.38 (m, 1H), 7.27–7.25 (m, 1H), 7.15–7.11 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 158.83 (d, J = 241.9 Hz), 147.3, 140.5, 129.7, 128.2, 122.2 (d, J = 11.3 Hz), 121.0, 120.6 (d, J = 8.8 Hz), 120.2 (d, J = 10.1 Hz), 118.6 (d, J = 29.0 Hz), 102.8 (d, J = 25.2 Hz).

5-Chloro-2-phenyl-2H-indazole (1c)

1c was prepared by the general procedure with 2-bromo-5-chlorobenzaldehyde. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.32 (s, 1H), 7.88–7.87 (m, 2H), 7.74 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 1.3 Hz, 1H), 7.54–7.52 (m, 2H), 7.43–7.40 (m, 1H), 7.27–7.25 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 148.0, 140.2, 129.6, 128.19, 128.16, 128.1, 123.1, 120.9, 119.9, 119.5, 119.0. HRMS (ESI): m/z calcd for C₁₃H₁₀ClN₂ [M + H]⁺ 229.0527. Found 229.0518.

5-Bromo-2-phenyl-2H-indazole (1d)³²

1d was prepared by the general procedure with 2,5-dibromobenzaldehyde. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.33 (s, 1H), 7.88–7.86 (m, 3H), 7.67 (d, J = 9.2 Hz, 1H), 7.54–7.51 (m, 2H), 7.43–7.40 (m, 1H), 7.38–7.36 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 148.3, 140.4, 130.7, 129.8, 128.4, 124.1, 122.7, 121.2, 120.0, 119.9, 116.1.

5-Methoxy-2-phenyl-2H-indazole (1e)³²

1e was prepared by the general procedure with 2-bromo-5-methoxybenzaldehyde. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.24 (s, 1H), 7.87–7.85 (m, 2H), 7.69 (d, J = 9.4 Hz, 1H), 7.51–7.48 (m, 2H), 7.38–7.35 (m, 1H), 7.05–7.03 (m, 1H), 6.88–6.87 (m, 1H), 3.84 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 155.8, 147.0, 140.8, 129.7, 127.7, 123.0, 122.2, 120.8, 119.5, 119.4, 96.5, 55.5.

6-Chloro-2-phenyl-2H-indazole (1f)³²

The 1f was prepared by the general procedure with 2-bromo-4-chlorobenzaldehyde. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.36 (s, 1H), 7.86 (d, J = 7.7 Hz, 2H), 7.78 (s, 1H), 7.62 (d, J = 8.9 Hz, 1H), 7.52 (t, J = 7.9 Hz, 2H), 7.40 (t, J = 7.4 Hz, 1H), 7.06–7.04 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 150.0, 140.4, 132.9, 129.8, 128.4, 124.2, 121.9, 121.3, 121.1, 121.0, 117.1.

6-Methyl-2-phenyl-2H-indazole (1g)¹⁷

The 1g was prepared by the general procedure with 2-bromo-4-methylbenzaldehyde. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.33 (s, 1H), 7.88 (d, J = 7.3 Hz, 2H), 7.59 (d, J = 8.6 Hz, 1H), 7.55–7.49 (m, 3H), 7.40–7.36 (m, 1H), 6.97–6.95 (m, 1H), 2.47 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 150.6, 140.7, 136.9, 129.6, 127.8, 125.6, 121.3, 121.0, 120.3, 120.0, 116.3, 22.4.

2-Phenyl-2H-[1,3]dioxolo[4,5-f]indazole (1h)¹⁷

1h was prepared by the general procedure with 6-bromobenzo[d][1,3]dioxole-5-carbaldehyde. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.18 (s, 1H), 7.82–7.80 (m, 2H), 7.50–7.46 (m, 2H), 7.35–7.31 (m, 1H), 7.04 (s, 1H), 6.88 (m, 1H), 5.96 (s, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 149.9, 147.6, 146.3, 140.7, 129.7, 127.3, 120.3, 119.9, 118.8, 101.2, 95.1, 94.4.

5-Fluoro-2-(p-tolyl)-2H-indazole (1i)³¹

1i was prepared by the general procedure. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.30 (s, 1H), 7.77–7.73 (m, 3H), 7.31–7.25 (m, 3H), 7.14–7.10 (m, 1H), 2.42 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 158.8 (d, J = 240.7 Hz), 147.2, 138.3, 138.2, 130.2, 122.1 (d, J = 11.3 Hz), 120.9, 120.5 (d, J = 8.8 Hz), 120.1 (d, J = 8.8 Hz), 118.4 (d, J = 29.0 Hz), 102.8 (d, J = 25.2 Hz), 21.13.

2-(4-Fluorophenyl)-2H-indazole (1j)³³

1j was prepared by the general procedure with 4-fluoroaniline. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.32 (s, 1H), 7.86–7.84 (m, 2H), 7.79 (d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.5 Hz, 1H), 7.34–7.31 (m, 1H), 7.22–7.19 (m, 2H), 7.14–7.11 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 162.1 (d, J = 248.2 Hz), 149.9, 137.0, 127.1, 122.9, 122.8 (d, J = 8.8 Hz), 122.7, 120.6, 120.5, 118.0, 116.5 (d, J = 22.7 Hz).

2-(3-Fluorophenyl)-2H-indazole (1k)³³

1k was prepared by the general procedure with 3-fluoroaniline. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.39 (s, 1H), 7.79–7.77 (m, 1H), 7.72–7.67 (m, 3H), 7.51–7.45 (m, 1H), 7.35–7.31 (m, 1H), 7.14–7.07 (m, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 163.2 (d, J = 246.0 Hz), 149.9, 141.9 (d, J = 10.0 Hz), 130.9 (d, J = 9.0 Hz), 127.3, 122.9, 120.5, 118.0, 116.1 (d, J = 3.0 Hz), 114.8, 114.6, 108.8, 108.6.

2-(4-Chlorophenyl)-2H-indazole (1l)³³

1l was prepared by the general procedure with 4-chloroaniline. Yellow solid; ¹H NMR (600 MHz, CDCl₃): δ 8.35 (s, 1H), 7.85–7.83 (m, 2H), 7.78–7.77 (m, 1H), 7.68 (d, J = 8.5 Hz, 1H), 7.49–7.46 (m, 2H), 7.34–7.32 (m, 1H), 7.13–7.10 (m, 1H); ¹³C {¹H} NMR (150 MHz, CDCl₃): δ 150.0, 139.2, 133.7, 129.8, 127.2, 123.0, 122.9, 122.1, 120.5, 120.4, 118.0.

2-(4-Bromophenyl)-2H-indazole (1m)¹⁷

1m was prepared by the general procedure with 4-bromoaniline. Yellow solid; ¹H NMR (600 MHz, CDCl₃): δ 8.35 (s, 1H), 7.79–7.76 (m, 3H), 7.69–7.67 (m, 1H), 7.64–7.62 (m, 2H), 7.34–7.31 (m, 1H), 7.13–7.10 (m, 1H), ¹³C {¹H} NMR (150 MHz, CDCl₃): δ 150.0, 139.6, 132.8, 127.3, 123.0, 122.9, 122.4, 121.6, 120.5, 120.3, 118.1.

2-(4-(Trifluoromethyl)phenyl)-2H-indazole (1n)³¹

1n was prepared by the general procedure with 4-(trifluoromethyl)aniline. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.46 (s, 1H), 8.06–8.04 (m, 2H), 7.80–7.77 (m, 3H), 7.71–7.69 (m, 1H), 7.37–7.33 (m, 1H), 7.15–7.11 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 150.3, 143.0, 129.9 (q, J = 33.0 Hz), 127.7, 127.0 (q, J = 3.0 Hz), 123.21, 123.15, 122.6, 120.9, 120.6, 120.6, 118.2.

2-(p-tolyl)-2H-indazole (1o)³¹

1o was prepared by the general procedure with p-toluidine. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.35 (s, 1H), 7.82–7.77 (m, 3H), 7.70 (d, J = 8.4 Hz, 1H), 7.34–7.30 (m, 3H), 7.13–7.10 (m, 1H), 2.42 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 149.6, 138.4, 138.0, 130.2, 126.8, 122.8, 122.4, 120.9, 120.43, 120.37, 118.0, 21.1.

2-(m-tolyl)-2H-indazole (1p)³⁴

1p was prepared by the general procedure with m-toluidine. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.40 (s, 1H), 7.81–7.76 (m, 2H), 7.72–7.70 (m, 1H), 7.67–7.65 (m, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.35–7.31 (m, 1H), 7.23–7.20 (m, 1H), 7.14–7.10 (m, 1H), 2.47 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 149.7, 140.5, 139.8, 129.4, 128.7, 126.8, 122.7, 122.4, 121.8, 120.5, 120.4, 118.0, 117.9, 21.5.

2-(o-Tolyl)-2H-indazole (1q)³⁴

1q was prepared by the general procedure with o-toluidine. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.10 (s, 1H), 7.83–7.81 (m, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.45–7.32 (m, 5H), 7.17–7.14 (m, 1H), 2.26 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 149.3, 140.4, 133.9, 131.3, 129.2, 126.62, 126.59, 126.4, 124.3, 122.2, 122.0, 120.3, 118.0, 17.9.

2-(4-Methoxyphenyl)-2H-indazole (1r)¹⁷

1r was prepared by the general procedure with 4-methoxyaniline. Yellow solid; ¹H NMR (500 MHz, CDCl₃): δ 8.29 (s, 1H), 7.79 (d, J = 8.7 Hz, 3H), 7.69 (d, J = 8.5 Hz, 1H), 7.33–7.30 (m, 1H), 7.10 (t, J = 7.5 Hz, 1H), 7.02–7.00 (m, 2H), 3.85 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 159.4, 149.7, 134.2, 126.6, 122.8, 122.5, 122.3, 120.41, 120.37, 117.9, 114.8, 55.7.

2-(4-(tert-Butyl)phenyl)-2H-indazole (1s)³⁵

1s was prepared by the general procedure with 4-(tert-butyl)aniline. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.38 (s, 1H), 7.84–7.79 (m, 3H), 7.72–7.70 (m, 1H), 7.55–7.52 (m, 2H), 7.34–7.31 (m, 1H), 7.14–7.10 (m, 1H), 1.38 (s, 9H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 151.3, 149.8, 138.2, 126.8, 126.6, 122.8, 122.4, 120.8, 120.5, 120.4, 118.0, 34.8, 31.4.

2-(4-(Methylthio)phenyl)-2H-indazole (1t)³¹

1t was prepared by the general procedure with 4-(methylthio)aniline. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.36 (s, 1H), 7.84–7.77 (m, 3H), 7.70–7.68 (m, 1H), 7.39–7.35 (m, 2H), 7.34–7.30 (m, 1H), 7.13–7.09 (m, 1H), 2.53 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 149.7, 138.7, 137.8, 127.3, 126.9, 122.8, 122.5, 121.3, 120.4, 120.2, 117.9, 15.9.

Ethyl 4-(2H-Indazol-2-yl)benzoate (1u)³¹

1u was prepared by the general procedure with ethyl 4-aminobenzoate. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.45 (s, 1H), 8.20–8.18 (m, 2H), 8.00–7.98 (m, 2H), 7.78–7.76 (m, 1H), 7.68 (d, J = 8.5 Hz, 1H), 7.34–7.31 (m, 1H), 7.13–7.10 (m, 1H), 4.41 (q, J = 7.1 Hz, 2H), 1.42 (t, J = 7.1 Hz, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 165.9, 150.4, 143.8, 131.3, 129.8, 127.6, 123.21, 123.15, 120.7, 120.4, 118.3, 61.5, 14.5.

2-(Pyridin-2-yl)-2H-indazole (1v)³¹

1v was prepared by the general procedure with pyridin-2-amine. White solid; ¹H NMR (500 MHz, CDCl₃): δ 9.10 (s, 1H), 8.49 (d, J = 4.6 Hz, 1H), 8.27 (d, J = 8.2 Hz, 1H), 7.86 (t, J = 7.8 Hz, 1H), 7.77–7.71 (m, 2H), 7.32 (t, J = 7.7 Hz, 1H), 7.26 (t, J = 6.1 Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 152.1, 150.5, 148.5, 139.0, 127.7, 122.91, 122.86, 122.6, 121.4, 120.8, 118.2, 114.3.

2-Cyclohexyl-2H-indazole (1w)¹⁷

1w was prepared by the general procedure with cyclohexanamine. White solid; ¹H NMR (400 MHz, CDCl₃): δ 7.94 (s, 1H), 7.73–7.71 (m, 1H), 7.66–7.64 (m, 1H), 7.29–7.25 (m, 1H), 7.08–7.04 (m, 1H), 4.43–4.36 (m, 1H), 2.29–2.24 (m, 2H), 1.98–1.88 (m, 4H), 1.80–1.76 (m, 1H), 1.54–1.42 (m, 2H), 1.37–1.26 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 148.2, 125.6, 121.41, 121.38, 120.2, 120.1, 117.4, 62.9, 34.0, 25.5, 25.4.

2-(3,5-Dimethylphenyl)-2H-indazole (1x)¹⁷

1x was prepared by the general procedure with 3,5-dimethylaniline. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.38 (s, 1H), 7.82–7.79 (m, 1H), 7.71–7.69 (m, 1H), 7.52 (s, 2H), 7.34–7.30 (m, 1H), 7.13–7.09 (m, 1H), 7.03 (m, 1H), 2.42 (s, 6H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 149.7, 140.5, 139.6, 129.7, 126.8, 122.7, 122.4, 120.6, 120.5, 118.9, 118.0, 21.5.

2-(3-Chloro-4-methylphenyl)-2H-indazole (1y)³⁶

1y was prepared by the general procedure with 3-chloro-4-methylaniline. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.35 (s, 1H), 7.94 (d, J = 2.1 Hz, 1H), 7.77 (d, J = 8.8 Hz, 1H), 7.69–7.67 (m, 2H), 7.36–7.31 (m, 2H), 7.11 (t, J = 7.5 Hz, 1H), 2.43 (s, 3H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 145.0, 139.5, 136.0, 135.5, 131.8, 127.2, 123.0, 122.8, 121.7, 120.6, 120.5, 119.0, 118.1, 19.9.

2-(3,4-Dichlorophenyl)-2H-indazole (1z)³⁷

1z was prepared by the general procedure with 3,4-dichloroaniline. White solid; ¹H NMR (500 MHz, CDCl₃): δ 8.34 (s, 1H), 8.06 (d, J = 2.6 Hz, 1H), 7.76–7.72 (m, 2H), 7.67 (d, J = 8.5 Hz, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.35–7.32 (m, 1H), 7.14–7.10 (m, 1H); ¹³C {¹H} NMR (125 MHz, CDCl₃): δ 150.1, 139.6, 133.7, 131.8, 131.2, 127.5, 123.04, 122.98, 122.6, 120.4, 120.3, 119.6, 118.0.

General Procedure for the Synthesis of α-Keto Acids³⁸

Aryl ketones (32 mmol) and SeO₂ (2 equiv., 7.10 g, 64 mmol) were added to a round-bottom flask under a nitrogen atmosphere. Then, degassed pyridine (30 mL) was added as the solvent. The reaction mixture was heated to 120 °C using an oil bath for 15 h. When reaction was finished, the reaction mixture was filtered and washed with EA, and the filtrate was collected and evaporated using a rotavapor. Saturated aqueous NaOH solution was added to this concentrated reaction mixture to adjust the pH to 12. Then, the aqueous phase was collected and extracted with EA and saturated NaCl solution. After the aqueous phase was collected and adjusted to pH < 2 using 2 M hydrochloric acid, the aqueous phase was extracted with EA. Then, the organic layer was collected, dried with anhydrous NaSO₄, and filtered before it was concentrated and purified by flash chromatography (EA and PE).

2-(4-Fluorophenyl)-2-oxoacetic Acid (2b)³⁹

2b was prepared by the general procedure with 1-(4-fluorophenyl)ethan-1-one. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.43–8.39 (m, 2H), 7.24–7.18 (m, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 182.7, 167.4 (d, J = 258.5 Hz), 161.9, 134.4 (d, J = 9.0 Hz), 128.2 (d, J = 2.9 Hz), 116.5 (d, J = 22.0 Hz).

2-(4-Chlorophenyl)-2-oxoacetic acid (2c)³⁸

2c was prepared by the general procedure with 1-(4-chlorophenyl)ethan-1-one. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.29–8.26 (m, 2H), 7.53–7.50 (m, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 183.4, 162.2, 142.8, 132.7, 130.2, 129.6.

2-(4-Bromophenyl)-2-oxoacetic Acid (2d)³⁹

2d was prepared by the general procedure with 1-(4-bromophenyl)ethan-1-one. White solid; ¹H NMR (400 MHz, CDCl₃): δ 8.22–8.19 (m, 2H), 7.70–7.67 (m, 2H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 183.6, 162.0, 132.7, 132.6, 131.8, 130.6.

2-(2-Fluorophenyl)-2-oxoacetic Acid (2e)¹⁷

2e was prepared by the general procedure with 1-(2-fluorophenyl)ethan-1-one. Brown solid; ¹H NMR (400 MHz, CDCl₃): δ 8.00–7.96 (m, 1H), 7.70–7.64 (m, 1H), 7.34–7.30 (m, 1H), 7.22–7.17 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 183.6, 166.4, 162.9 (d, J = 258.0 Hz), 137.2 (d, J = 9.0 Hz), 131.4, 125.0 (d, J = 3.0 Hz), 121.3 (d, J = 10.0 Hz), 116.9 (d, J = 21.0 Hz).

2-Oxo-2-(2-(trifluoromethyl)phenyl)acetic Acid (2f)¹⁷

2f was prepared by the general procedure with 1-(2-(trifluoromethyl)phenyl)ethan-1-one. Brown liquid; ¹H NMR (400 MHz, CDCl₃): δ 7.78–7.75 (m, 1H), 7.68–7.67 (m, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 187.6, 162.2, 132.5, 132.1, 130.1, 129.0 (q, J = 33.0 Hz), 127.2 (q, J = 5.0 Hz), 123.6 (q, J = 272.0 Hz).

2-Oxo-2-(p-tolyl)acetic Acid (2g)³⁹

The 2g was prepared by the general procedure with 1-(p-tolyl)ethan-1-one. Brown solid; ¹H NMR (400 MHz, CDCl₃): δ 8.21 (d, J = 8.0 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.45 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 184.2, 162.9, 147.4, 131.5, 129.9, 129.4, 22.2.

2-Oxo-2-(m-tolyl)acetic Acid (2h)¹⁷

2h was prepared by the general procedure with 1-(m-tolyl)ethan-1-one. Brown liquid; ¹H NMR (400 MHz, CDCl₃): δ 7.98–7.91 (m, 2H), 7.48–7.36 (m, 2H), 2.40 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 186.1, 165.0, 139.0, 136.4, 132.0, 131.1, 129.0, 128.2, 21.3.

2-(3-Methoxyphenyl)-2-oxoacetic Acid (2i)¹⁷

The 2i was prepared by the general procedure with 1-(3-methoxyphenyl)ethan-1-one. Yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 7.85 (d, J = 7.8 Hz, 2H), 7.43 (t, J = 7.9 Hz, 1H), 7.26–7.22 (m, 1H), 3.87 (s, 3H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 185.1, 163.5, 160.0, 133.1, 130.2, 124.2, 122.7, 114.3, 55.7.

2-(Benzo[d][1,3]dioxol-5-yl)-2-oxoacetic Acid (2j)³⁹

2j was prepared by the general procedure with 1-(benzo[d][1,3]dioxol-5-yl)ethan-1-one. White solid; ¹H NMR (400 MHz, (CD₃)₂SO): δ 7.54–7.51 (m, 1H), 7.38 (d, J = 1.7 Hz, 1H), 7.12 (d, J = 8.2 Hz, 1H), 6.20 (s, 2H); ¹³C {¹H} NMR (100 MHz, (CD₃)₂SO): δ 186.9, 166.3, 153.4, 148.5, 127.7, 126.4, 108.7, 107.3, 102.7.

2-(Naphthalen-2-yl)-2-oxoacetic Acid (2k)³⁹

2k was prepared by the general procedure with 1-(naphthalen-2-yl)ethan-1-one. Yellow solid; ¹H NMR (400 MHz, CDCl₃): δ 9.10 (s, 1H), 8.20–8.17 (m, 1H), 8.03 (d, J = 8.2 Hz, 1H), 7.94–7.88 (m, 2H), 7.70–7.66 (m, 1H), 7.62–7.58 (m, 1H); ¹³C {¹H} NMR (100 MHz, CDCl₃): δ 184.4, 162.4, 136.7, 135.7, 132.4, 130.6, 130.3, 129.1, 128.03, 127.99, 127.4, 124.8.

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.4c00176.

• Investigation of the large-scale reaction, product inhibition effect, UV/vis spectra, luminescence quenching, headspace gas analysis, and ¹H/¹³C {¹H} NMR spectra (PDF)

The authors declare no competing financial interest.