Visible-Light-Induced Organophotoredox-Catalyzed Phosphonylation

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Visible-Light-Induced Organophotoredox Catalyzed Phosphonylation of 2H-Indazoles with Diphenylphosphine Oxide Mukta Singsardar, Amrita Dey, Rajib Sarkar, and Alakananda Hajra J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02019 • Publication Date (Web): 24 Sep 2018 Downloaded from http://pubs.acs.org on September 24, 2018

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The Journal of Organic Chemistry

Visible-Light-Induced Organophotoredox-Catalyzed Phosphonylation of 2HIndazoles with Diphenylphosphine Oxide Mukta Singsardar,† Amrita Dey,† Rajib Sarkar, and Alakananda Hajra* Department of Chemistry, Visva-Bharati (A Central University), Santiniketan 731235, India †

Both the author contributed equally in this work Email: [email protected]

ABSTRACT A metal-free visible-light-induced phosphonylation of 2H-indazoles with diphenylphosphine oxide has been developed using rose bengal as an organophotoredox catalyst under ambient air at room temperature. A library of diphenyl(2-phenyl-2H-indazol-3-yl)phosphine oxide with broad functionalities has been synthesized in high yields. The experimental result suggests the radical pathway of the reaction.

INTRODUCTION Indazoles are an essential group of N-heterocycles which have gained a great importance in the field of medicinal and organic chemistry as they exhibit numerous pharmaceutical and biological activities.1 Effective bioactivities like anti-tumor, anti-microbial, anti-depressant, antiinflammatory, anti-HIV, anti-platelet etc. of 2H-indazole make it much useful in pharmacological purposes.2 Besides, being an efficient bioisostere of indoles and benzimidazoles, it is an interesting core moiety in various marketed drugs like MK-4827 (anticancer agent),3a bendazac,3b pazopanib (votrient, tyrosine kinase inhibitor),3c and

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gamendazole3d (Fig 1). Recently it was also applied as selective estrogen receptors4a and bacterial gyrase B inhibitors.4b Though there are few strategies for the preparation of indazole core moiety,5 the functionalization of indazoles are very limited.6

Fig 1. Biologically active molecules having 2H-indazole scaffold. Likewise, phosphine-containing aromatic compounds are found to be widely applicable in organic synthesis, materials science and also in inorganic chemistry as the presence of phosphorous controls the physical, chemical, and biological properties of the adjacent arenes.7 A number of biologically active compounds containing carbon-phosphorus bond, specially N-C-P bond, acquire a huge capacity of influencing the physiological and pathological processes with broad applications in medicinal field.8 In this circumstances transition-metal catalyzed strategies of C-P bond formation involving terminal alkynes or substituted alkenes with P-H species have been well established.9 However, limited number of methodologies for direct phosphonylation of different heterocyclic moieties have been developed.10 Most of these methodologies required the use of expensive transition metals, selective ligands, external oxidants and high temperature. Therefore, we became interested to develop an efficient and environmentally benign method for the direct construction of C(sp2)-P bond under metal-free condition. Organic dyes being less toxic, less expensive, and easy to handle are useful as good as transition-metal complexes in photoredox 2 ACS Paragon Plus Environment

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catalyzed reactions.11 In recent years, photoredox-based P-radical reactions have been developed to synthesize a range of organophosphorus compounds.12 Wu and his group have developed a photocatalysis cross-coupling C(sp2)-H phosphorylation of thiazole derivatives using white LED (Scheme 1a).13 Remarkably, Xie and coworkers have also developed a strategy to produce substituted alkenylphosphine oxides from alcohols employing Rhodamine B and Bronsted acid as co-operative catalytic system under white LED (Scheme 1b).14 However, there is no report for the phosphonylation of indazole derivatives. On the basis of our experiences on functionalization of heterocyclic moieties,15,16 we envisaged that the phosphonylation of indazoles could be carried out with diphenylphosphine oxide under visible-light-mediated photoredox catalysis. Herein, we report a direct and environmentally friendly method for the C(sp2)-H phosphonylation of indazoles using rose bengal as an organophotoredox catalyst irradiated with blue LED under ambient air at room temperature (Scheme 1c). Scheme 1. Photoredox Catalysis toward C-P Bond Formation



RESULTS AND DISCUSSION In the initial study, we have chosen 2-phenyl-2H-indazole (1a) (0.2 mmol) and diphenylphosphine oxide (2a) (0.3 mmol) as model substrates employing DBU (2.0 equiv) as base with 3 mol % rose bengal as a photocatalyst in CH3CN irradiated with 34 W blue LED under ambient air at room temperature. Delightfully, diphenyl(2-phenyl-2H-indazol-3yl)phosphine oxide (3a) was obtained in 48% yield after 16 h (Table 1, entry 1). Then the effect of other solvents like 1,2-DCE, DMSO, and DMF was checked but CH3CN was found to be more competent among these (Table 1, entries 2-4). Interestingly, the yield of the desired product was increased to 75% when a binary solvent CH3CN/H2O (1.0/0.14 mL) mixture was used as reaction medium (Table 1, entry 5). It was observed that the organophotocatalyst rose bengal worked effectively in water and acetonitrile medium due to its solubility and kinetic effects.17 Further screening of the proportion of the solvents revealed that 1.0/0.18 mL CH3CN/H2O mixture was the best option affording the product (3a) in excellent yield (Table 1, entry 6). Then, other photocatalysts including eosin Y and eosin B were also tested (Table 1, entries 7 and 8) but lower yields were obtained with these photocatalysts. The catalytic effect of Ru(bpy)3Cl2·6H2O and Ir(ppy)3 photoredox catalysts were checked for this transformation. In presence Ru(bpy)3Cl2·6H2O trace amount of product was obtained whereas Ir(ppy)3 provided 60% yield of the product (see SI, Table S1, entries 18 and 19). Subsequently the reaction was also performed with the bases like DABCO and Et3N. It was observed that these were not as effective as DBU for the formation of 3a (Table 1, entries 9 and 10). The reaction did not proceed without any base (Table 1, entry 11). Decreasing or increasing the loading of rose bengal (see SI, Table S1, entries 24 and 25) or changing the proportion of the two substrates was not helpful (see SI, Table S1, entries 26 and 27). Decreasing the loading of base also decreased the yield of the product (see SI, Table S1, entry 28). Then the reaction was carried out in the absence of photoredox catalyst and 4 ACS Paragon Plus Environment

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also in dark, in both the cases phosphonylation product 3a was not generated (Table 1, entries 12 and 13). Moreover, the formation of the product was diminished under inert atmosphere (Table 1, entry 14). These results indicated that the photoredox process is a fundamental route in this reaction and the aerial oxygen is necessary for the oxidation. The phosphonylation was tried with lower-power white LED (10 W). However, formation of the desired product was not observed. No significant temperature change was observed during the reaction. Finally, the maximum yield (88%) of the desired product was obtained in this optimized reaction condition by using 3 mol % rose bengal with 2.0 equiv DBU in CH3CN/H2O (1.0/0.18 mL) irradiated with 34 W blue LED for 16 h under ambient air at room temperature (Table 1, entry 6). Table 1. Optimization of the Reaction Conditionsa

entry

photocatalyst (mol %)

base (equiv)

solvent (1 mL)

yield (%)b

1

rose bengal

DBU

CH3CN

48

2

rose bengal

DBU

1,2- DCE

38

3

rose bengal

DBU

DMSO

trace

4

rose bengal

DBU

DMF

trace

5

rose bengal

DBU

CH3CN/H2O (1.0/0.14 mL)

75

6

rose bengal

DBU

CH3CN/H2O (1.0/0.18 mL)

88

7

eosin Y

DBU

CH3CN/H2O (1.0/0.18 mL)

32

8

eosin B

DBU

CH3CN/H2O (1.0/0.18 mL)

20



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9

rose bengal

DABCO

CH3CN/H2O (1.0/0.18 mL)

45

10

rose bengal

Et3N

CH3CN/H2O (1.0/0.18 mL)

42

11

rose bengal

-

CH3CN/H2O (1.0/0.18 mL)

NR

12

-

DBU

CH3CN/H2O (1.0/0.18 mL)

NR

13c

rose bengal

DBU

CH3CN/H2O (1.0/0.18 mL)

NR

14d

rose bengal

DBU

CH3CN/H2O (1.0/0.18 mL)

trace

a

Reaction conditions: All reactions were carried out with 1a (0.2 mmol), 2a (0.3 mmol), photocatalyst (3 mol %), base (2.0 equiv), and solvent (1.0 mL) irradiated with 34 W blue LED for 16 h under air at room temperature. bYields. NR = no reaction. cIn dark. dUnder argon atmosphere. After getting the optimized reaction condition in hand, we planned to examine the scope of this protocol with different functionalities in 2H-indazole system. We first checked the electronic effect of N-2 substituent of 2H-indazoles and the results are summarized in Scheme 2. 2-Phenyl-2H-indazole bearing electron donating group like 4-Me and 4-OMe at the phenyl ring efficiently reacted to provide good yield of the desired products (3b and 3c). As well as 2-(mtolyl)-2H-indazole underwent smoothly by giving 90% yield (3d). 2H-Indazoles containing halogens such as 4-F, 4-Cl, 3-Cl, and 4-Br in phenyl ring successfully involved under the present reaction conditions to give the desired products in excellent yields (3f-3h). 2H-Indazole with dihalogenated phenyl ring also gave 84% yield of the product (3i). Similarly, the methylenedioxy group performed well in this reaction (3j, 89%). Notably, pyridine substituted derivative afforded good result in this standardized reaction condition (3k, 90%). 2-(4-Methoxybenzyl)-2Hindazole as well as 2-(tert-butyl)-2H-indazole also worked well in this reaction protocol to give good yields of the desired products (3l and 3m). 2H-Indazole having electron withdrawing group such as -NO2 in phenyl ring did not respond in this reaction. 2H-Indazole also did not react with diethyl phosphite, diphenyl phosphite, and ethyl phenylphosphinate under the present condition. 6 ACS Paragon Plus Environment

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To verify the practical applicability of the current methodology the gram-scale reaction was also performed in the usual laboratory setup using 2-phenyl-2H-indazole (1a). The diphenyl(2phenyl-2H-indazol-3-yl)phosphine oxide (3a) was obtained without significant decrease in yield. Scheme 2. Substrate Scopes with Variation of N-2 Substituents on 2H-Indazolea,b

a

Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), rose bengal (3 mol %), DBU (2.0 equiv), and CH3CN/H2O (1.0 mL) irradiated with 34 W blue LED for 16 h under ambient air at room temperature. bYields. c5 mmol scale. Next, the scope of substrates with various substitutions in the arene part of 2H-indazoles was studied (Scheme 3). 5-OMe Substituted different 2H-indazoles with 4-Me and 4-OMe in the N-phenyl ring provided the desired products (3n and 3o) in good to excellent yields. 5,6Dimethoxy substituted derivative also gave 70% yield of the product (3p). Similarly, halo substituted 2H-indazole at C-5 position (5-F and 5-Cl) reacted well to produce the desired products (3q-3t) with moderate to high yields. However, the current methodology is not applicable for indole moiety.



Scheme 3. Substrate Scopes with Variation of Arene Substituents on 2H-Indazolea,b

a

Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), rose bengal (3 mol %), DBU (2.0 equiv), and CH3CN/H2O (1.0 mL) irradiated with 34 W blue LED for 16 h under air at room temperature. b Yields. Furthermore, the scope of substrates with variation in phosphine oxide was considered (Scheme 4). Bis(4-methoxyphenyl)phosphine oxide reacted well with 2-(p-tolyl)-2H-indazole and 2-(4-chlorophenyl)-2H-indazole providing the desired products (5a and 5b) in good yields. Di-p-tolylphosphine oxide also performed well with 2-(4-fluorophenyl)-2H-indazole and 2-(4bromophenyl)-2H-indazole to give the corresponding products (5c and 5d) in good yields. Di(thiophen-2-yl)phosphine oxide also reacted with 2-(p-tolyl)-2H-indazole gave 83% yield of the product (5e). Phosphine oxides with electron-donating groups (-OMe and -Me) at ortho and meta positions in phenyl ring reacted smoothly with 2-(p-tolyl)-2H-indazole providing the desired products in excellent yields (5f-5h). Phosphine oxide bearing electron-withdrawing group (-F) at para position also afforded the product in 88% yield (5i). Scheme 4. Substrate Scopes with Variation of Phosphine Oxidea,b


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a

Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), rose bengal (3 mol %), DBU (2.0 equiv), and CH3CN/H2O (1.0 mL) irradiated with 34 W blue LED for 16 h under air at room temperature. b Yields. To acquire the mechanistic insights into the reaction pathway, few control experiments were carried out (Scheme 5). It was found that 2-phenyl-2H-indazole (1a) failed to give the corresponding phosphonylation product (3a) in the presence of radical scavengers including 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO), 2,6-di-tert-butyl-4-methyl phenol (BHT) and pbenzoquinone (BQ). These observations imply that the reaction proceeds through a radical pathway. Scheme 5. Control Experiments

Based on the control experiments (Scheme 5) and literature reports,11d,12a,b,16a a plausible mechanism for the formation of phosphonylation product is depicted here in Scheme 6. Firstly,



RB is converted to its excited state RB* upon absorption of photon. Then RB* oxidized the indazole (1a) to indazole radical cation (A) along with formation of photocatalyst radical anion RB•− through a single electron transfer (SET) process. After that the photocatalyst radical anion RB•− is oxidized to RB by reducing O2 to superoxide radical anion (O2•−). Thereafter, the intermediate P-centered diphenylphosphinoyl radical (B) would be generated through HAT (hydrogen atom transfer) process between highly active superoxide radical anion (O2•−) and diphenylphosphine oxide (2a) in presence of DBU and then undergoes intermolecular addition with indazole radical cation (A) to form cation intermediate C. Phosphonylation did not occur in DBU. This suggests that DBU cannot act as a competitor of indazoles and it acts only as a base. Finally, the deprotonation process occurred by HO2− from intermediate C to afford the phosphonylation product 3a along with H2O2. Presence of H2O2 was detected by starch-iodine test.11h The formation of the desired product is completely stopped in presence of pbenzoquinone, which acts as a superoxide radical anion scavenger.11i Scheme 6. Plausible Mechanistic Pathway


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N N 1a

h

Cl

RB

RB*

Cl

Cl

Cl

COONa I

I

RB

NaO

O2

RB O2 N

O P Ph Ph B

+

N A Ph O P Ph H N N

DBU

O I

O I

O Ph H P Ph 2a

Ph O P Ph

HO2

N N

C

H2 O 2

3a

CONCLUSION In summary, we have developed a metal-free visible-light-induced organophotoredox catalyzed radical phosphonylation of indazoles using rose bengal as a photocatalyst under aerobic reaction conditions. A variety of phosphonylated indazoles have been synthesized in high to excellent yields. To the best of our knowledge this is the first report of visible-light-promoted functionalization of indazoles. The further development of related photo-induced oxidative Cheteroatom bond forming reactions is ongoing in our laboratory.

EXPERIMENTAL SECTION General Information: All reagents were purchased from commercial sources and used without further purification. 1H NMR spectra were determined on 400 MHz spectrometer as solutions in CDCl3. Chemical shifts are expressed in parts per million (δ) and the signals were reported as s (singlet), d (doublet), t (triplet), m (multiplet), dd (doublet of doublet), and coupling constants (J) 11 ACS Paragon Plus Environment


were given in Hz. 13C{1H} and

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P NMR spectra were recorded at 100 and 162 MHz in CDCl3

solution. Chemical shifts are referenced to CDCl3 (δ = 7.26 for 1H and δ = 77.16 for

13

C{1H}

NMR) as internal standard. TLC was done on silica gel coated glass slide. All solvents were dried and distilled before use. Commercially available solvents were freshly distilled before the reaction. All reactions involving moisture sensitive reactants were executed using oven dried glassware. All 2-substituted indazoles were prepared by the reported method.5c,6a General experimental procedure for the synthesis of 3: Indazoles (0.2 mmol), diphenylphosphine oxide (0.3 mmol, 61 mg), rose bengal (3 mol %, 6 mg), DBU (2.0 equiv, 61 mg) were taken in an oven-dried reaction vessel equipped with a magnetic stir bar. Then 1 mL of the CH3CN/H2O (1.0/0.18 mL) solvent was added and the reaction mixture was irradiated using a 34 W blue LED at room temperature under open atmosphere for 16 h. The progress of the reaction was monitored by TLC. After completion, the reaction mixture was quenched with 10 mL water/ethyl acetate (1:3). Then the reaction mixture was extracted with ethyl acetate and the organic phase was dried over anhydrous Na2SO4. After evaporating the solvent under reduced pressure the crude residue was obtained. Finally it was purified by column chromatography on silica gel (60-120 mesh) using petroleum ether/ethylacetate as an eluent to afford the pure products. Diphenyl(2-phenyl-2H-indazol-3-yl)phosphine oxide (3a): Gummy solid (69 mg, 88%), Rf 0.5 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.86-7.84 (m, 1H), 7.68-7.63 (m, 4H), 7.52-7.47 (m, 4H), 7.40-7.36 (m, 4H), 7.32-7.28 (m, 1H), 7.26-7.20 (m, 3H), 6.94-6.91 (m, 1H), 6.31 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.9 (d, JC-P = 12.0 Hz), 140.7, 132.5, 132.3, 131.9 (d, JC-P = 10.0 Hz), 131.4, 129.3, 128.7 (d, JC-P = 13.0 Hz), 128.5, 127.9 (d, JC-P = 14.0 Hz), 127.0, 126.6, 124.3, 120.5, 118.6;

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P NMR (CDCl3, 162 MHz): δ 12.6HRMS

(ESI-TOF) m/z: [M + H]+ Calcd for C25H20N2OP 395.1308; Found 395.1306. 12 ACS Paragon Plus Environment

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Diphenyl(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (3b): Gummy solid (66 mg, 81%), Rf 0.5 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.86-7.83 (m, 1H), 7.67-7.62 (m, 4H), 7.52-7.48 (m, 2H), 7.41-7.34 (m, 6H), 7.31-7.27 (m, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.94-6.90 (m, 1H), 6.33 (d, J = 9.2 Hz, 1H), 2.28 (s, 3H) ; 13C{1H} NMR (CDCl3, 100 MHz): δ 148.8 (d, JC-P = 12.0 Hz), 139.3, 138.3, 132.6, 132.3, 131.9 (d, JC-P = 10.0 Hz), 131.5, 129.1, 128.7 (d, JC-P = 12 .0Hz), 127.8 (d, JC-P = 15.0 Hz), 127.1, 126.7, 126.4, 124.2, 120.5, 118.6, 21.2;

31

P NMR

(CDCl3, 162 MHz): δ 12.9; Anal. Calcd for C26H21N2OP: C, 76.46; H, 5.18; N, 6.86; Found C, 76.64; H, 5.09; N, 6.66%. (2-(4-Methoxyphenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3c): Gummy solid (69 mg, 82%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.85-7.82 (m, 1H), 7.68-7.63 (m, 4H), 7.52-7.48 (m, 2H), 7.41-7.37 (m, 6H), 7.30-7.26 (m, 1H), 6.93-6.89 (m, 1H), 6.71-6.69 (m, 2H), 6.29 (d, J = 8.4 Hz, 1H), 3.76 (s, 3H) ;

13

C{1H} NMR (CDCl3, 100 MHz): δ 160.1,

148.8 (d, JC-P = 12.0 Hz), 133.8, 132.6, 132.3 (d, JC-P = 3.0 Hz), 131.9 (d, JC-P = 10.0 Hz), 131.4, 128.8, 128.6, 128.2, 127.8, 126.4, 124.2, 120.4, 118.5, 113.6, 55.6; 31P NMR (CDCl3, 162 MHz): δ 12.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C26H22N2O2P 425.1413; Found 425.1415. Diphenyl(2-(m-tolyl)-2H-indazol-3-yl)phosphine oxide (3d): Gummy solid (73 mg, 90%), Rf 0.55 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.99-7.96 (m, 1H), 7.82-7.77 (m, 4H), 7.64-7.60 (m, 2H), 7.53-7.49 (m, 4H), 7.46-7.39 (m, 2H), 7.36 (s, 1H), 7.24 (t, J = 8.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H), 7.07-7.04 (m, 1H), 6.50 (d, J = 8.8 Hz, 1H), 2.34 (s, 3H);

13

C{1H}

NMR (CDCl3, 100 MHz): δ 148.8, 140.6, 138.5, 132.6, 132.2 (d, JC-P = 3.0 Hz), 131.8 (d, JC-P = 10.0 Hz), 131.5, 130.0, 128.6 (d, JC-P = 13.0 Hz), 128.4, 127.9, 127.8, 127.5, 126.5, 124.2, 124.0, 120.5, 118.5, 21.1; 31P NMR (CDCl3, 162 MHz): δ 12.6; Anal. Calcd for C26H21N2OP: C, 76.46; H, 5.18; N, 6.86; Found C, 76.30; H, 5.22; N, 6.62%.



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(2-(4-Fluorophenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3e): Gummy solid (73 mg, 89%), Rf 0.55 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.85-7.82 (m, 1H), 7.69-7.63 (m, 4H), 7.55-7.47 (m, 4H), 7.43-7.39 (m, 4H), 7.32-7.28 (m, 1H), 6.94-6.87 (m, 3H), 6.25 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 162.8 (d, JC-F = 248.0 Hz), 148.9, 136.8 (d, JC-P = 2.0 Hz), 132.5 (d, JC-P = 2.0 Hz), 132.3, 131.9 (d, JC-P = 10.0 Hz), 131.2, 129.0, 128.9 (d, JC-F = 3.0 Hz), 128.7, 127.6, 126.7, 124.4, 120.4, 118.6, 115.4 (d, JC-F = 23.0 Hz);

31

P NMR

(CDCl3, 162 MHz): δ 12.6; Anal. Calcd for C25H18FN2OP: C, 72.81; H, 4.40; N, 6.79; Found C, 73.00; H, 4.35; N, 6.68%. (2-(4-Chlorophenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3f): Gummy solid (74 mg, 86%), Rf 0.6 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.84-7.82 (m, 1H), 7.68-7.63 (m, 4H), 7.55-7.50 (m, 2H), 7.47-7.45 (m, 2H), 7.43-7.38 (m, 4H), 7.31-7.27 (m, 1H), 7.20-7.17 (m, 2H), 6.94-6.90 (m, 1H), 6.26 (d, J = 8.8 Hz, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 149.0 (d, JC-P = 11.0 Hz), 139.2, 135.3, 132.5 (d, JC-P = 3.0 Hz), 132.2, 131.9 (d, JC-P = 10.0 Hz), 131.1, 128.9, 128.7 (d, JC-P = 13.0 Hz), 128.2, 127.8 (d, JC-P = 14.0 Hz), 127.5, 126.8, 124.5, 120.3, 118.5; 31P NMR (CDCl3, 162 MHz): δ 12.8; Anal. Calcd for C25H18ClN2OP: C, 70.02; H, 4.23; N, 6.53; Found C, 70.25; H, 4.13; N, 6.42%. (2-(3-Chlorophenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3g): Gummy solid (66 mg, 77%), Rf 0.65 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.85-7.82 (m, 1H), 7.71-7.66 (m, 4H), 7.56-7.51 (m, 3H), 7.44-7.40 (m, 5H), 7.33-7.29 (m, 1H), 7.24-7.16 (m, 2H), 6.95-6.92 (m, 1H), 6.29 (d, J = 8.8 Hz, 1H);

13

C{1H} NMR (CDCl3, 100 MHz): δ 134.2, 132.6, 132.2,

131.9 (d, JC-P = 10.0 Hz), 129.5 (d, JC-P = 7.0 Hz), 128.9, 128.8, 127.2, 126.9, 125.3, 124.6, 120.5, 118.6; 31P NMR (CDCl3, 162 MHz): δ 12.5; Anal. Calcd for C25H18ClN2OP: C, 70.02; H, 4.23; N, 6.53; Found C, 70.18; H, 4.30; N, 6.64%.


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(2-(4-Bromophenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3h): Gummy solid (82 mg, 87%), Rf 0.6 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.85-7.82 (m, 1H), 7.68-7.63 (m, 4H), 7.56-7.52 (m, 2H), 7.44-7.39 (m, 6H), 7.36-7.25 (m, 3H), 6.94-6.91 (m, 1H), 6.30-6.26 (m, 1H);

13

C{1H} NMR (CDCl3, 100 MHz): δ 149.1 (d, JC-P = 11.0 Hz), 139.8, 137.6, 132.5,

132.3, 131.9 (d, JC-P = 10.0 Hz), 131.6, 131.2, 128.9 (d, JC-P = 13.0 Hz), 128.6, 128.5, 126.8, 124.5, 123.5, 120.4, 118.6; 31P NMR (CDCl3, 162 MHz): δ 12.7; Anal. Calcd for C25H18BrN2OP: C, 63.44; H, 3.83; N, 5.92; Found C, 63.61; H, 3.76; N, 5.84%. (2-(3-Chloro-4-fluorophenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3i): Gummy solid (75 mg, 84%), Rf 0.55 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.83-7.81 (m, 1H), 7.717.65 (m, 4H), 7.58-7.48 (m, 4H), 7.46-7.41 (m, 4H), 7.33-7.29 (m, 1H), 7.03-6.99 (m, 1H), 6.956.91 (m, 1H), 6.25 (d, J = 8.8 Hz, 1H);

13

C{1H} NMR (CDCl3, 100 MHz): δ 158.3 (d, JC-F =

251.0 Hz), 149.0 (d, JC-P = 12.0 Hz), 137.1 (d, JC-P = 3.0 Hz), 132.7 (d, JC-P = 3.0 Hz), 132.0, 131.9 (d, JC-P = 10.0 Hz), 130.9, 129.5, 129.0, 128.9 (d, JC-P = 13.0 Hz), 127.9, 127.7 (d, JC-P = 14.0 Hz), 127.1 (d, JC-F = 9.0 Hz), 127.0, 124.7, 121.0 (d, JC-P = 19.0 Hz), 120.3, 118.6, 116.2 (d, JC-F = 22.0 Hz); 31P NMR (CDCl3, 162 MHz): δ 12.6; Anal. Calcd for C25H17ClFN2OP: C, 67.20; H, 3.83; N, 6.27; Found C, 67.05; H, 3.74; N, 6.38%. (2-(Benzo[d][1,3]dioxol-5-yl)-2H-indazol-3-yl)diphenylphosphine oxide (3j): Gummy solid (78 mg, 89%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.84-7.81 (m, 1H), 7.707.65 (m, 4H), 7.55-7.51 (m, 2H), 7.44-7.39 (m, 4H), 7.31-7.27 (m, 1H), 7.03-7.01 (m, 1H), 6.946.90 (m, 1H), 6.87 (d, J = 2.0 Hz, 1H), 6.61 (d, J = 8.4 Hz, 1H), 6.33 (d, J = 8.8 Hz, 1H), 5.92 (s, 2H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.6 (d, JC-P = 47.0 Hz), 147.3, 134.7, 132.5, 132.4 (d, JC-P = 3.0 Hz), 132.2, 131.9 (d, JC-P = 10.0 Hz), 131.4, 128.8 (d, JC-P = 13.0 Hz), 126.6, 124.3, 122.6, 121.3, 120.5, 118.5, 107.8 (d, JC-P = 63.0 Hz), 101.9;


31

P NMR (CDCl3, 162 MHz): δ


Page 16 of 29

12.7; Anal. Calcd for C26H19N2O3P: C, 71.23; H, 4.37; N, 6.39; Found C, 71.39; H, 4.22; N, 6.44%. Diphenyl(2-(pyridin-2-yl)-2H-indazol-3-yl)phosphine oxide (3k): Gummy solid (71 mg, 90%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 8.01-7.99 (m, 2H), 7.85-7.83 (m, 1H), 7.76-7.70 (m, 5H), 7.50-7.46 (m, 2H), 7.42-7.37 (m, 4H), 7.32-7.28 (m, 1H), 7.13-7.10 (m, 1H), 6.96-6.92 (m, 1H), 6.66 (d, J = 8.8 Hz, 1H) ;

13

C{1H} NMR (CDCl3, 100 MHz): δ 147.1,

138.4, 133.3, 132.4, 132.2, 132.1, 131.8 (d, JC-P = 2.0 Hz), 131.6 (d, JC-P = 10.0 Hz), 128.7, 128.5 (d, JC-P = 13.0 Hz), 128.2, 127.2, 124.7, 123.6, 121.5, 118.8, 117.9; 31P NMR (CDCl3, 162 MHz): δ 17.6; Anal. Calcd for C24H18N3OP: C, 72.90; H, 4.59; N, 10.63; Found C, 72.77; H, 4.61; N, 10.66%. (2-(4-Methoxybenzyl)-2H-indazol-3-yl)diphenylphosphine oxide (3l): Gummy solid (58 mg, 67%), Rf 0.45 (PET : EtOAc = 1:1); 1H NMR (CDCl3, 400 MHz): δ 9.22 (d, J = 8.4 Hz, 1H), 8.32-8.30 (m, 2H), 8.07 (d, J = 8.8 Hz, 1H), 7.94-7.89 (m, 5H), 7.58-7.54 (m, 4H), 7.51-7.46 (m, 5H), 6.96-6.94 (m, 2H), 3.87 (s, 3H);

13

C{1H} NMR (CDCl3, 100 MHz): δ 151.9, 134.6, 132.3

(d, JC-P = 9.0 Hz), 132.3 (d, JC-P = 3.0 Hz), 131.3, 130.2, 129.2, 128.6, 128.4, 127.6, 127.3, 125.3, 114.1, 55.5, 21.8; 31P NMR (CDCl3, 162 MHz): δ 27.9; Anal. Calcd for C27H23N2O2P: C, 73.96; H, 5.29; N, 6.39; Found C, 74.07; H, 5.34; N, 6.30%. (2-(tert-Butyl)-2H-indazol-3-yl)diphenylphosphine oxide (3m): Gummy solid (47 mg, 63%), Rf 0.4 (PET : EtOAc = 2:3); 1H NMR (CDCl3, 400 MHz): δ 8.34 (d, J = 2.0 Hz, 1H), 7.93-7.88 (m, 3H), 7.71-7.66 (m, 3H), 7.49-7.45 (m, 4H), 7.40-7.35 (m, 3H), 1.47 (s, 9H);

13

C{1H} NMR

(CDCl3, 100 MHz): δ 133.1, 132.5, 132.4, 132.3, 132.2, 132.1 (d, JC-P = 3.0 Hz), 131.4 (d, JC-P = 2.0 Hz), 128.7 (d, JC-P = 13.0 Hz), 128.4, 128.3, 127.9 (d, JC-P = 12.0 Hz), 124.4, 124.3, 122.2 (d,


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JC-P = 3.0 Hz), 121.3, 119.3, 30.2, 30.0;

31

P NMR (CDCl3, 162 MHz): δ 29.8;Anal. Calcd for

C23H23N2OP: C, 73.78; H, 6.19; N, 7.48; Found C, 73.57; H, 6.29; N, 7.55%. (5-Methoxy-2-(p-tolyl)-2H-indazol-3-yl)diphenylphosphine oxide (3n): Gummy solid (62 mg, 71%), Rf 0.5 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.70-7.64 (m, 5H), 7.49-7.47 (m, 2H), 7.42-7.35 (m ,6H), 6.99-6.94 (m, 3H), 5.48 (d, J = 2.4 Hz, 1H), 3.33 (s, 3H), 2.26 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 156.5, 145.5, 139.1, 138.4, 132.9, 132.18 (d, JC-P = 3.0 Hz), 132.11, 132.0, 131.8, 129.0, 128.7, 128.6, 128.5, 126.6, 125.4, 121.6, 119.7, 96.8, 55.0, 21.2;

31

P NMR (CDCl3, 162 MHz): δ 12.6; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for

C27H24N2O2P 439.1570; Found 439.1573. (5-Methoxy-2-(4-methoxyphenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3o): Gummy solid (81 mg, 89%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.71-7.65 (m, 5H), 7.49-7.47 (m, 2H), 7.43-7.39 (m, 6H), 6.97-6.94 (m, 1H), 6.70-6.67 (m, 2H), 5.46 (d, J = 2.0 Hz, 1H), 3.75 (s, 3H), 3.33 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 159.9, 156.5, 145.5, 133.9, 132.8, 132.2 (d, JC-P = 2.0 Hz), 132.1 (d, JC-P = 9.0 Hz), 131.7, 128.7 (d, JC-P = 13.0 Hz), 128.4, 128.1, 121.5, 119.7, 113.6, 96.8, 55.6, 55.0;

31

P NMR (CDCl3, 162 MHz): δ 12.5; Anal.

Calcd for C27H23N2O3P: C, 71.36; H, 5.10; N, 6.16; Found C, 71.20; H, 5.04; N, 6.27%. (5,6-Dimethoxy-2-phenyl-2H-indazol-3-yl)diphenylphosphine oxide (3p): Gummy solid (63 mg, 70%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.71-7.66 (m, 4H), 7.547.52 (m, 2H), 7.49-7.45 (m, 2H), 7.41-7.37 (m, 4H), 7.20-7.18 (m, 3H), 7.07 (d, J = 1.6 Hz, 1H), 5.47 (s, 1H), 3.92 (s, 3H), 3.38 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 151.5, 149.2, 145.7 (d, JC-P = 12.0 Hz), 140.8, 132.8, 132.2, 132.0 (d, JC-P = 10.0 Hz), 131.6, 128.8, 128.6 (d, JC-P = 12.0 Hz), 126.7, 123.5, 97.6, 96.1, 56.0, 55.6; 31P NMR (CDCl3, 162 MHz): δ 12.4; Anal. Calcd for C27H23N2O3P: C, 71.36; H, 5.10; N, 6.16; Found C, 71.54; H, 5.07; N, 6.07%.



Page 18 of 29

(5-Fluoro-2-(p-tolyl)-2H-indazol-3-yl)diphenylphosphine oxide (3q): Gummy solid (71 mg, 83%), Rf 0.5 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.82-7.80 (m, 2H), 7.66-7.61 (m, 4H), 7.54-7.50 (m, 2H), 7.42-7.40 (m, 3H), 7.34 (d, J = 8.0 Hz, 2H), 7.12-7.06 (m, 1H), 7.00 (d, J = 8.0 Hz, 2H), 5.83 (dd, J = 2.4, 10.4 Hz, 1H), 2.28 (s, 3H);

13

C{1H} NMR (CDCl3, 100

MHz): δ 159.4 (d, JC-F = 241.0 Hz), 146.1 (d, JC-P = 12.0 Hz), 139.5, 138.2, 132.4 (d, JC-F = 3.0 Hz), 132.3, 131.8 (d, JC-P = 10.0 Hz), 131.7, 131.1, 130.2, 129.1, 128.8 (d, JC-P = 13.0 Hz), 128.6, 126.6, 123.4, 121.0, 120.6 (d, JC-F = 10.0 Hz), 118.1 (d, JC-P = 28.0 Hz), 103.5 (d, JC-F = 27.0 Hz), 21.2; 31P NMR (CDCl3, 162 MHz): δ 12.8;Anal. Calcd for C26H20FN2OP: C, 73.23; H, 4.73; N, 6.57; Found C, 73.59; H, 4.87; N, 6.40%. (5-Fluoro-2-(4-methoxyphenyl)-2H-indazol-3-yl)diphenylphosphine oxide (3r): Gummy solid (74 mg, 84%), Rf 0.4 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.83-7.77 (m, 2H), 7.67-7.62 (m, 4H), 7.55-7.51 (m, 2H), 7.44-7.37 (m, 5H), 7.11-7.06 (m, 1H), 6.71-6.69 (m, 2H), 5.81-5.78 (m, 1H), 3.76 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 133.7, 132.5 (d, JC-F = 2.0 Hz), 132.3, 132.2, 131.8 (d, JC-P = 10.0 Hz), 131.7, 131.1, 128.9 (d, JC-P = 12.0 Hz), 128.7, 128.6, 128.1, 122.5, 120.7 (d, JC-P = 10.0 Hz), 118.1 (d, JC-P = 29.0 Hz), 114.7, 113.7, 103.4 (d, JC-F = 27.0 Hz), 55.6;

31

P NMR (CDCl3, 162 MHz): δ 12.6; Anal. Calcd for C26H20FN2O2P: C,

70.58; H, 4.56; N, 6.33; Found C, 70.60; H, 4.62; N, 6.29%. (5-Chloro-2-phenyl-2H-indazol-3-yl)diphenylphosphine oxide (3s): Gummy solid (64 mg, 75%), Rf 0.6 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.78 (d, J = 9.2 Hz, 1H), 7.677.62 (m, 4H), 7.55-7.48 (m, 4H), 7.43-7.39 (m, 4H), 7.25-7.22 (m, 4H), 6.19 (s, 1H);

13

C{1H}

NMR (CDCl3, 100 MHz): δ 140.5, 132.6 (d, JC-P = 3.0 Hz), 132.3, 131.9 (d, JC-P = 10.0 Hz), 130.9, 129.5, 128.9, 128.8, 128.6, 128.5, 128.1, 126.9, 119.8 (d, JC-P = 52.0 Hz);

31

P NMR

(CDCl3, 162 MHz): δ 12.7; Anal. Calcd for C25H18ClN2OP: C, 70.02; H, 4.23; N, 6.53; Found C, 69.89; H, 4.09; N, 6.46%. 18 ACS Paragon Plus Environment

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(2-(Benzo[d][1,3]dioxol-5-yl)-5-chloro-2H-indazol-3-yl)diphenylphosphine oxide (3t): Gummy solid (62 mg, 66%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.77-7.74 (m, 1H), 7.69-7.63 (m, 4H), 7.57-7.54 (m, 2H), 7.47-42 (m, 4H), 7.24-7.22 (m, 1H), 7.01-6.99 (m, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.61 (d, J = 8.4 Hz, 1H), 6.21 (d, J = 2.0 Hz, 1H), 5.93 (s, 2H); 13

C{1H} NMR (CDCl3, 100 MHz): δ 134.4, 132.6 (d, JC-P = 2.0 Hz), 132.0 (d, JC-P = 10.0 Hz),

130.2, 128.9 (d, JC-P = 12.0 Hz), 128.6, 128.1, 121.2, 119.7 (d, JC-P = 51.0 Hz), 107.7 (d, JC-P = 47.0 Hz), 102.0; 31P NMR (CDCl3, 162 MHz): δ 12.7; Anal. Calcd for C26H18ClN2O3P: C, 66.04; H, 3.84; N, 5.92; Found C, 65.84; H, 3.92; N, 5.81%. Bis(4-methoxyphenyl)(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (5a): Gummy solid (77 mg, 82%), Rf 0.5 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.83 (d, J = 8.8 Hz, 1H), 7.557.50 (m, 4H), 7.33-7.26 (m, 3H), 7.02 (d, J = 8.0 Hz, 2H), 6.97-6.93 (m, 1H), 6.89-6.86 (m, 4H), 6.50 (d, J = 8.8 Hz, 1H), 3.82 (s, 6H), 2.30 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 162.7 (d, JC-P = 2.0 Hz), 148.6, 139.2, 138.5, 133.7 (d, JC-P = 11.0 Hz), 129.0, 127.8, 127.6, 126.7, 126.4, 124.3, 124.0, 123.1, 120.7, 118.4, 114.2 (d, JC-P = 13.0 Hz), 55.5, 21.2; 31P NMR (CDCl3, 162 MHz): δ 13.6; Anal. Calcd for C28H25N2O3P: C, 71.79; H, 5.38; N, 5.98; Found C, 71.61; H, 5.49; N, 5.88%. (2-(4-Chlorophenyl)-2H-indazol-3-yl)bis(4-methoxyphenyl)phosphine oxide (5b): Gummy solid (77 mg, 79%), Rf 0.55 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.83-7.80 (m, 1H), 7.56-7.51 (m, 4H), 7.45-7.43 (m, 2H), 7.32-7.28 (m, 1H), 7.22-7.20 (m, 2H), 6.98-6.94 (m, 1H), 6.92-6.89 (m, 4H), 6.44 (d, J = 8.8 Hz, 1H), 3.84 (s, 6H);

13

C{1H} NMR (CDCl3, 100

MHz): δ 162.9, 148.9 (d, JC-P = 12.0 Hz), 139.4, 135.2, 133.7 (d, JC-P = 11.0 Hz), 128.6, 128.3, 127.9, 127.8, 127.7, 126.7, 124.3, 123.8, 122.7, 120.7, 118.5, 114.4 (d, JC-P = 14.0 Hz), 55.5; 31P NMR (CDCl3, 162 MHz): δ 13.2; Anal. Calcd for C27H22ClN2O3P: C, 66.33; H, 4.54; N, 5.73; Found C, 66.52; H, 4.49; N, 5.81%. 19 ACS Paragon Plus Environment


(2-(4-Fluorophenyl)-2H-indazol-3-yl)di-p-tolylphosphine oxide (5c): Gummy solid (70 mg, 80%), Rf 0.5 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.83-7.81 (m, 1H), 7.54-7.46 (m, 6H), 7.31-7.27 (m, 1H), 7.21-7.19 (m, 4H), 6.95-6.89 (m, 3H), 6.35 (d, J = 8.8 Hz, 1H), 2.38 (s, 6H);

13

C{1H} NMR (CDCl3, 100 MHz): δ 162.7 (d, JC-F = 248.0 Hz), 148.8 (d, JC-P = 12.0

Hz), 143.0 (d, JC-P = 3.0 Hz), 136.9 (d, JC-F = 3.0 Hz), 131.8 (d, JC-P = 10.0 Hz), 129.5 (d, JC-P = 13.0 Hz), 129.3, 129.2, 128.9 (d, JC-F = 8.0 Hz), 128.1, 127.7, 127.5, 126.6, 124.2, 120.6, 118.4, 115.3 (d, JC-F = 24.0 Hz), 21.7;

31

P NMR (CDCl3, 162 MHz): δ 13.4; Anal. Calcd for

C27H22FN2OP: C, 73.63; H, 5.03; N, 6.36; Found C, 73.81; H, 5.00; N, 6.25%. (2-(4-Bromophenyl)-2H-indazol-3-yl)di-p-tolylphosphine oxide (5d): Gummy solid (81 mg, 81%), Rf 0.6 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.83-7.81 (m, 1H), 7.53-7.48 (m, 4H), 7.39-7.33 (m, 4H), 7.32-7.28 (m, 1H), 7.22-7.19 (m, 4H), 6.96-6.92 (m, 1H), 6.40 (d, J = 8.8 Hz, 1H), 2.39 (s, 6H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.9, 143.1 (d, JC-P = 3.0 Hz), 139.8, 131.8 (d, JC-P = 10.0 Hz), 131.5, 129.5 (d, JC-P = 13.0 Hz), 129.3, 129.1, 128.5, 128.1, 127.9, 127.7, 126.8, 124.3, 123.4, 120.7, 118.5, 21.7; 31P NMR (CDCl3, 162 MHz): δ 13.7; Anal. Calcd for C27H22BrN2OP: C, 64.68; H, 4.42; N, 5.59; Found C, 64.84; H, 4.36; N, 5.71%. Di(thiophen-2-yl)(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (5e): Gummy solid (70 mg, 83%), Rf 0.5 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.86-7.83 (m, 1H), 7.74-7.71 (m, 2H), 7.49-7.46 (m, 2H), 7.37-7.30 (m, 3H), 7.14-7.12 (m, 2H), 7.09 (d, J = 8.4 Hz, 2H), 7.05-7.01 (m, 1H), 6.55 (d, J = 8.8 Hz, 1H), 2.35 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 139.5, 138.3, 137.1 (d, JC-P = 12.0 Hz), 134.6 (d, JC-P = 6.0 Hz), 129.1, 128.5, 128.4, 126.8, 126.6, 124.6, 120.2, 118.6, 105.1, 21.3;

31

P NMR (CDCl3, 162 MHz): δ -0.8; Anal. Calcd for

C22H17N2OPS2: C, 62.84; H, 4.08; N, 6.66; Found C, 62.69; H, 4.10; N, 6.57%.


Page 20 of 29

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Bis(3-methoxyphenyl)(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (5f): Gummy solid (80 mg, 86%), Rf 0.5 (PET : EtOAc = 7:3); 1H NMR (CDCl3, 400 MHz): δ 7.85-7.82 (m, 1H), 7.35-7.33 (m, 2H), 7.31-7.25 (m, 4H), 7.23-7.22 (m, 1H), 7.16-7.11 (m, 2H), 7.03-7.00 (m, 4H), 6.97-6.93 (m, 1H), 6.43 (d, J = 9.2 Hz, 1H), 3.75 (s, 6H), 2.30 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 159.7 (d, JC-P = 16.0 Hz), 148.8, 139.3, 138.3, 133.8, 132.7, 129.9, 129.8, 129.0, 127.7 (d, JC-P = 15.0 Hz), 126.8, 126.5, 124.2, 124.0 (d, JC-P = 10.0 Hz), 120.5, 118.7 (d, JC-P = 3.0 Hz), 118.5, 116.6 (d, JC-P = 11.0 Hz), 55.5, 21.2;

31


C28H25N2O3P: C, 71.79; H, 5.38; N, 5.98; Found C, 71.60; H, 5.42; N, 5.85%. Di-o-tolyl(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (5g): Gummy solid (70 mg, 80%), Rf 0.55 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 8.59 (s, 1H), 8.00-7.97 (m, 1H), 7.747.72 (m, 2H), 7.46-7.42 (m, 2H), 7.34-7.25 (m, 4H), 7.15-7.09 (m, 3H), 7.09-6.97 (m, 3H), 2.56 (s, 6H), 2.39 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 149.3 (d, JC-P = 9.0 Hz), 143.7 (d, JC-P = 7.0 Hz), 138.3, 138.0, 133.0 (d, JC-P = 13.0 Hz), 132.2, 132.1, 131.2, 130.1, 128.9, 128.8, 125.7 (d, JC-P = 13.0 Hz), 125.6 (d, JC-P = 13.0 Hz), 125.3, 124.3, 123.0, 122.4, 122.2, 121.0, 21.99, 21.95, 21.1;

31

P NMR (CDCl3, 162 MHz): δ 34.9; Anal. Calcd for C28H25N2OP: C, 77.05; H,

5.77; N, 6.42; Found C, 76.89; H, 5.86; N, 6.31%. Di-m-tolyl(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (5h): Gummy solid (76 mg, 87%), Rf 0.45 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.85-7.83 (m, 1H), 7.50 (d, J = 13.2 Hz, 2H), 7.40-7.34 (m, 3H), 7.31-7.27 (m, 5H), 7.25-7.22 (m, 1H), 7.00 (d, J = 8.0 Hz, 2H), 6.95-6.91 (m, 1H), 6.41 (d, J = 8.8 Hz, 1H), 2.30 (s, 6H), 2.28 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.8 (d, JC-P = 12.0 Hz), 139.2, 138.6, 138.5, 138.3, 133.0 (d, JC-P = 2.0 Hz), 132.49, 132.43, 132.3, 131.3, 128.9, 128.8, 128.6, 128.4, 127.7 (d, JC-P = 15.0 Hz), 126.7, 126.4, 124.0, 120.7, 118.4, 21.4, 21.2;

31


C28H25N2OP: C, 77.05; H, 5.77; N, 6.42; Found C, 77.21; H, 5.68; N, 6.37%. 21 ACS Paragon Plus Environment


Bis(4-fluorophenyl)(2-(p-tolyl)-2H-indazol-3-yl)phosphine oxide (5i): Gummy solid (78 mg, 88%), Rf 0.5 (PET : EtOAc = 3:2); 1H NMR (CDCl3, 400 MHz): δ 7.86-7.84 (m, 1H), 7.66-7.59 (m, 4H), 7.35-7.29 (m, 3H), 7.10-7.02 (m, 6H), 7.00-6.96 (m, 1H), 6.40 (d, J = 8.8 Hz, 1H), 2.30 (s, 3H);

13

C{1H} NMR (CDCl3, 100 MHz): δ 165.3 (d, JC-F = 257.0 Hz), 148.8 (d, JC-P = 13.0

Hz), 139.6, 138.1, 134.36, 134.35 (d, JC-F = 21.0 Hz), 129.1, 128.4, 127.8 (d, JC-P = 16.0 Hz), 127.3, 126.6 (d, JC-F = 3.0 Hz), 124.6, 120.1, 118.7, 116.3 (d, JC-F = 13.0 Hz), 116.1, 116.0, 21.2; 31

P NMR (CDCl3, 162 MHz): δ 11.2; Anal. Calcd for C26H19F2N2OP: C, 70.27; H, 4.31; N, 6.30;

Found C, 70.43; H, 4.39; N, 6.16%.

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]. Notes The authors declare no competing financial interest

ACKNOWLEDGMENT A.H. acknowledges the financial support from CSIR, New Delhi (Grant no. 02(0307)/17/EMRII). M. S. thanks UGC-New Delhi for NFHE, A.D. thanks CSIR for her fellowship, and R. S. thanks SERB-DST for NPDF.

.

ASSOCIATED CONTENT Supporting information Scanned copies of 1H,

13

C{1H}, and

31

P NMR spectra of the synthesized compounds are

available as supporting information. This material is available free of charge via the Internet at http://pubs.acs.org. 22 ACS Paragon Plus Environment

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Visible-Light-Induced Organophotoredox-Catalyzed Phosphonylation

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