Supporting Information

Supporting Information Cobalt-Catalyzed Carbonylation of C(sp 2 )-H Bonds with Azodicarboxylate as the Carbonyl Source Jiabin Ni,, Jie Li,,š Zhoulong Fan,, and Ao Zhang *,,,š CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory (SOMCL), Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China University of Chinese Academy of Sciences, Beijing 100049, China š ShanghaiTech University, Shanghai 20120, China E-mail: aozhang@simm.ac.cn Table of Content 1. General Information... S2 2. Structures of Starting Materials... S3 3. Procedure for the Preparation of Starting Material 1s... S3 4. Procedure for the Preparation of D 5 -N-(quinolin-8-yl)benzamide... S4 5. Procedure for the Preparation of Potential Intermediate Compounds 4... S5 6. Optimization of the Reaction Conditions.... S6 7. General Procedure for Carbonylation of Aromatic Amides... S6 8. KIE Experiments... S7 9. Radical Trapping Experiments... S10 10. HRMS Analysis of the Crude Reaction Solution... S11 11. Control Experiments for the Transformation of Key Intermediate 4 to 3a... S11 12. Control Experiment Using CO Instead of DIAD... S12 13. Determine the Extrusion of CO From the Reaction... S12 14. Characterization Data for the Products... S13 15. References... S21 16. Copies of NMR Spectra Data... S22 S1

1. General Information All reactions were performed in flame-dried glassware using sealed tube or Schlenk tube. Liquids and solutions were transferred with syringes. All solvents and chemical reagents were obtained from commercial sources and used without further purifications. 1 H and 13 C NMR spectra were recorded with tetramethylsilane as an internal reference. Low and high-resolution mass spectra were obtained in the EI or ESI mode. Flash column chromatography on silica gel (200-300 mesh) was used for the routine purification of reaction products. The column output was monitored by TLC on silica gel (100-200 mesh) precoated on glass plates (15 x 50 mm), and spots were visualized by UV light at 254 or 365 nm. Commercially available chemicals were obtained from Adamas-beta, Acros Organics, Strem Chemicals, Alfa Aesar, J&K and TCI. Starting materials (N-(quinolin-8-yl)benzamide) were prepared according to the literature procedures. [1] S2

2. Structures of Starting Materials 3. Procedure for the Preparation of Starting Material 1s The mixture of 3,5-dichlorobenzoic acid (955 mg, 5.0 mmol, 1.0 equiv.), 8-aminoquinoline (865 mg, 6.0 mmol, 1.2 equiv.), HOAt (1.02 g, 7.5 mmol, 1.5 equiv.), HATU (3.8 g, 10.0 mmol, 2.0 S3

equiv.) and DIPEA (5.0 ml, 30.0 mmol, 6.0 equiv.) in anhydrous DCM (40 ml) was stirred at room temperature overnight. Then the mixture was extracted with NH 4 Cl saturated solution (3 x 20 ml), and the organic layer was washed with water (20 ml) and brine (20 ml), dried over anhydrous NaSO 4 and concentrated under reduced pressure. The residue was purified on a silica gel column with petroleum ether/ethyl acetate (1/10) as the eluent to afford the title compound 1s (1.3 g, 82%). 3,5-Dichloro-N-(quinolin-8-yl)benzamide (1s). White solid, mp: 142-144 C, 1.3g, yield: 82%. 1 H NMR (400 MHz, CDCl 3 ) δ 10.66 (brs, 1H), 8.91 8.85 (m, 2H), 8.21 (dd, J = 8.3, 1.7 Hz, 1H), 7.93 (d, J = 1.9 Hz, 2H), 7.64 7.60 (m, 2H), 7.57 (dd, J = 3.7, 1.8 Hz, 1H), 7.51 (dd, J = 8.3, 4.2 Hz, 1H); 13 C NMR (126 MHz, CDCl 3 ) δ 162.7, 148.5, 138.6, 138.0, 136.5, 135.7, 133.9, 131.7, 128.0, 127.4, 125.9, 122.3, 121.9, 116.9; Ms (ESI): m/z = 317.2 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 16 H 11 Cl 2 N 2 O, 317.0243; Found, 317.0244. 4. Procedure for the Preparation of D 5 -N-(quinolin-8-yl)benzamide [1c] A round-bottom flask equipped with a stir bar and a condenser was charged with d 8 -tolune (99.9 atom % D) (5g, 50 mmol), KMnO 4 (20g, 125 mmol), Na 2 CO 3 (2.64g, 25 mmol), and H 2 O (150 ml). The reaction mixture was refluxed for 8 h and then cooled to room temperature. The mixture was filtered through a pad of celite, and the filtrate was acidified with 12 M HCl and extracted with DCM (3 30 ml). The organic layer was washed with water and concentrated under vacuum. S4

The crude product was recrystallized from water to give C 6 D 5 CO 2 H as white needle solid (4g, 64%). Synthesis of the amide 1a-d 5 from C 6 D 5 CO 2 H was performed using a similar procedure as above. [1] 5. Procedure for the Preparation of Potential Intermediate Compounds 4 A 10-fold excess of dry isopropanol (15.31 ml) was added to phthalic anhydride (S1, 2.96 g, 20 mmol) in a 150 ml round-bottom flask. The resulting solution was heated under reflux for 5 h. The mixture was then cooled to room temperature and concentrated under reduced pressure to give compound S2, which was used directly for the next step without further purification. [2] Synthesis of amide 4 was performed by following a similar procedure as that for the synthesis of N-(quinolin-8-yl)benzamide 1s from corresponding substituted benzoic acids. [1] Isopropyl 2-(quinolin-8-ylcarbamoyl)benzoate (4). Pale yellow oil, 5g, yield: 75 % (From S1). 1 H NMR (400 MHz, CDCl 3 ) δ 10.06 (brs, 1H), 8.95 (dd, J = 7.4, 1.0 Hz, 1H), 8.75 (dd, J = 4.2, 1.7 Hz, 1H), 8.18 (dd, J = 8.3, 1.7 Hz, 1H), 8.01 (dd, J = 7.7, 1.1 Hz, 1H), 7.68 (dd, J = 7.5, 1.3 Hz, 1H), 7.63 (dd, J = 7.4, 1.4 Hz, 1H), 7.61 7.58 (m, 1H), 7.56 (ddd, J = 7.4, 4.1, 1.5 Hz, 2H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 5.15 (m, 1H), 1.14 (d, J = 6.3 Hz, 6H); 13 C NMR (126 MHz, CDCl 3 ) δ 167.6, 166.0, 148.2, 138.5, 138.4, 136.3, 134.7, 132.0, 130.3, 129.8, 129.8, 127.9, 127.5, 127.4, 121.8, 121.6, 116.7, 69.2, 21.5; Ms (ESI): m/z = 335.4 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 20 H 19 N 2 O 3, 335.1390; Found, 335.1399. S5

6. Optimization of the Reaction Conditions. [a] entry [Co] catalyst oxidant additive solvent yield[%] [b] 1 Co(OAc) 2 4H 2 O Ag 2 CO 3 / 1,4-dioxane 66 2 Co(acac) 2 Ag 2 CO 3 / 1,4-dioxane 36 3 Co(acac) 3 Ag 2 CO 3 / 1,4-dioxane trace 4 Co(OAc) 2 4H 2 O Ag 2 CO 3 Na 2 CO 3 1,4-dioxane 86 5 Co(OAc) 2 4H 2 O Ag 2 CO 3 K 2 CO 3 1,4-dioxane 10 6 Co(OAc) 2 4H 2 O Ag 2 CO 3 Cs 2 CO 3 1,4-dioxane 0 7 Co(OAc) 2 4H 2 O Ag 2 CO 3 PivOH 1,4-dioxane 88 8 Co(OAc) 2 4H 2 O Ag 2 CO 3 AcOH 1,4-dioxane 70 9 Co(OAc) 2 4H 2 O Ag 2 CO 3 PivOH toluene 47 10 Co(OAc) 2 4H 2 O Ag 2 CO 3 PivOH DCE 18 11 Co(OAc) 2 4H 2 O AgOAc PivOH 1,4-dioxane 78 12 Co(OAc) 2 4H 2 O Ag 2 O PivOH 1,4-dioxane 83 13 Co(OAc) 2 4H 2 O Oxone PivOH 1,4-dioxane 62 14 [c] Co(OAc) 2 4H 2 O Ag 2 CO 3 PivOH 1,4-dioxane 79 15 [d] Co(OAc) 2 4H 2 O Ag 2 CO 3 PivOH 1,4-dioxane 76 16 [e] Co(OAc) 2 4H 2 O Ag 2 CO 3 PivOH 1,4-dioxane 69 [a] Reactions were carried out by using 1a (0.10 mmol), 2a (0.20 mmol), Co(OAc) 2 4H 2 O (20 mol%), oxidant (0.20 mmol), additive (0.20 mmol), solvent (1.0 ml), 100 ⁰C, air, 16h. PivOH = Pivalic acid. [b] Isolated yield. [c] PivOH (1 equiv.). [d] At 110 ⁰C. [e] At 90 ⁰C. 7. General Procedure for Carbonylation of Aromatic Amides To a dried tube (15 ml), N-(quinolin-8-yl)benzamide 1 (0.2 mmol), azadicarboxylate 2 (0.4 mmol), Co(OAc) 2 4H 2 O (10.0 mg, 0.04 mmol), Ag 2 CO 3 (110.3 mg, 0.4 mmol), PivOH (40.8 mg, 0.4 mmol), and 1,4-dioxane (2.0 ml) were added under air. The tube was sealed and the mixture was stirred for 16 h at 100 ⁰C. The mixture was then cooled to room temperature, diluted with dichloromethane, filtered through a celite pad, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc/Petroleum ether (1:4 ~ S6

1:2, v/v), to afford corresponding products 3. 8. KIE Experiments 8.1 Intermolecular Competition To a dried tube (15 ml) was added substrate 1a (0.10 mmol), 1a-d 5 (0.10 mmol), DIAD (0.40 mmol), Co(OAc) 2 4H 2 O (10mg, 0.040 mmol), Ag 2 CO 3 (110.3 mg, 0.40 mmol), PivOH (40.8 mg, 0.40 mmol), and 1,4-dioxane (2.0 ml) under air atmosphere. The tube was sealed and the mixture was stirred for 1 h at 100 ⁰C. The mixture was then cooled to room temperature, diluted with DCM, filtered through a celite pad, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: PE/EA = 2/1) to afford the desired product (yield = 55%). The ratio of product 3a/3a-d 4 was analyzed by 1 H NMR. S7

S8

8.2 Parallel Reactions O H N H 1a 0.1 mmol N + O O N N O O 2a 0.2 mmol Co(OAc) 2 4H 2 O(20 mol %) Ag 2 CO 3 (2 equiv) PivOH (2 equiv) 1,4-dioxane, air, 100 C O N O N 3a D D D D O D N H 1a-d 5 0.1 mmol N + O O N N O O 2a 0.2 mmol Co(OAc) 2 4H 2 O(20 mol %) Ag 2 CO 3 (2 equiv) PivOH (2 equiv) 1,4-dioxane, air, 100 C K H /K D =1.39 3a-d 4 D D D D O O N N To a dried tube (15 ml) was added substrate 1a (0.10 mmol) or 1a-d 5 (0.10 mmol), DIAD (0.20 mmol), Co(OAc) 2 4H 2 O (5mg, 0.020 mmol), Ag 2 CO 3 (55 mg, 0.20 mmol), PivOH (21 mg, 0.20 mmol), and 1,4-dioxane (1.0 ml) under air atmosphere. The mixture was stirred at 100 ⁰C in a sealed tube with a rubber plug. A periodic aliquot (50 µl) was removed by a syringe and concentrated, 1 H NMR analysis using CH 3 CN as an internal standard. The concentration of product was shown below: Time (min) [3a] (mmol/l) [3a-d 4 ] (mmol/l) 10 24.88 32.40 20 32.08 37.80 30 36.40 42.12 40 42.88 45.36 50 45.76 48.60 60 52.24 51.84 S9

The calculated K H /K D = 1.39. 9. Radical Trapping Experiments An oven-dried tube (15 ml) was charged with N-(quinolin-8-yl)benzamide 1a (0.10 mmol), DIAD (0.20 mmol), Co(OAc) 2 4H 2 O (5.0 mg, 0.020 mmol), Ag 2 CO 3 (55.2 mg, 0.20 mmol), PivOH (21 mg, 0.20 mmol), TEMPO (2.0 equiv/ 6.0 equiv/ 8.0 equiv) or BHT (88mg, 0.40 mmol) and 1,4-dioxane (1.0 ml) under air atmosphere. The tube was sealed and the mixture was stirred for 16 h at 100 ⁰C. After cooling to room temperature, the mixture was diluted with DCM, filtered through a celite pad, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: PE/EA = 2/1) to afford product 3a. S10

10. HRMS Analysis of the Crude Reaction Solution N-(Quinolin-8-yl)benzamide (1a, 0.20 mmol), DIAD (2a, 0.40 mmol), Co(OAc) 2 4H 2 O (10.0 mg, 0.040 mmol), Ag 2 CO 3 (110.3 mg, 0.40 mmol), PivOH (40.8 mg, 0.40 mmol) and 1,4-dioxane (2.0 ml) were added to a 15 ml Schlenk tube at the preheated oil bath under 100 ⁰C. After 1h, the reaction solution was detected by HPLC-HRMS. The ortho-c-h esterification product 4 was observed by HPLC-HRMS analysis of the reaction solution (Figure S1). According to the HRMS result, we carefully searched for the intermediate 4 by TLC analysis and successfully isolated it in 4.5% yield (3 mg) through column chromatography. The spectral data were in accordance with the prepared compound 4 as in the procedure 5. Figure S1 HRMS analysis of the crude reaction solution 11. Control Experiments for the Transformation of Key Intermediate 4 to 3a S11

An oven-dried 15 ml tube was charged with 4 (33.4 mg, 0.1 mmol), Co(OAc) 2 4H 2 O (5.0 mg, 0.02 mmol), Ag 2 CO 3 (55.2 mg, 0.2 mmol), PivOH (40.8 mg, 0.2 mmol) and 1,4-dioxane (1.0 ml) under air atmosphere. The tube was sealed and the mixture was stirred for 16 h at 100 ⁰C. After cooling to room temperature, the mixture was diluted with DCM, filtered through a celite pad, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: PE/EA = 2/1) to afford product 3a (14 mg) in 51% yield. The reaction was then repeated in the absence of 1Co(OAc) 2 4H 2 O, or 2Ag 2 CO 3, or 3Co(OAc) 2 4H 2 O and Ag 2 CO 3 both, affording products 3a in 47%, 62%, or <5% yields, respectively. 12. Control Experiment Using CO Instead of DIAD An oven-dried 15 ml tube equipped with a magnetic stir bar was charged with N-(quinolin-8-yl)benzamide (1a, 0.20 mmol), Co(OAc) 2 4H 2 O (10.0 mg, 0.040 mmol), Ag 2 CO 3 (110.3 mg, 0.40 mmol), and PivOH (40.8 mg, 0.40 mmol). After flushing with nitrogen for 5 min (vigorous stirring), deoxygenated 1,4-dioxane (2 ml) was added, and the reaction mixture was purged with CO gas for 10 min. The flask was then equipped with CO balloon and stirred for 16 h at 100 ⁰C. After cooling to room temperature, the mixture was diluted with DCM, filtered through a celite pad, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (eluent: PE/EA = 2/1) to afford product 3a (32 mg) in 58% yield. 13. Determine the Extrusion of CO From the Reaction [3] a) For the detection of evolution of CO in the standard reaction: a strip containing PdCl 2 and PMA (phosphomolybdic acid) was hanged from the neck of the reaction flask as shown below. The initial yellow color of the strip before the reaction (Figure S2) turned blue after 3 h of the reaction progress (Figure S3). The color change confirms the extrusion of CO from the reaction. S12

Figure S2 PdCl 2-PMA test strip before reaction Figure S3 PdCl 2-PMA test strip after reaction b) To the standard reaction system with the absence of DIAD, a strip containing PdCl 2 and PMA (phosphomolybdic acid) was hanged from the neck of the reaction flask as shown below. The initial yellow color of the strip (Figure S4) didn t change after 3 h of the reaction progress (Figure S5). The result indicated that there is no extrusion of CO in the absence of DIAD. Figure S4 PdCl 2-PMA test strip before reaction Figure S5 PdCl 2-PMA test strip after reaction 14. Characterization Data for the Products 2-(Quinolin-8-yl)isoindoline-1,3-dione (3a). White solid, 46 mg, 84% yield. (This compound is known [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.1, 1.6 Hz, 1H), 8.21 (dd, J = 8.3, 1.5 Hz, 1H), 8.02 7.97 (m, 2H), 7.95 (dd, J = 8.2, 1.1 Hz, 1H), 7.82 7.77 (m, 2H), 7.75 (dd, J = 7.3, 1.3 S13

Hz, 1H), 7.69 7.63 (m, 1H), 7.43 (dd, J = 8.3, 4.2 Hz, 1H); Ms (ESI): m/z = 275.4 [M+H] +. 5-Methyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3b). White solid, 49 mg, 85% yield. (This compound is known [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.2, 1.7 Hz, 1H), 8.22 (dd, J = 8.3, 1.7 Hz, 1H), 7.96 (dd, J = 8.2, 1.5 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H), 7.82 7.80 (m, 1H), 7.75 (dd, J = 7.3, 1.5 Hz, 1H), 7.69 7.65 (m, 1H), 7.60 (ddd, J = 7.7, 1.4, 0.7 Hz, 1H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 2.57 (s, 3H); Ms (ESI): m/z = 289.3 [M+H] +. 5-(tert-Butyl)-2-(quinolin-8-yl)isoindoline-1,3-dione (3c). White solid, 47 mg, 71% yield. (This compound is known [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.2, 1.6 Hz, 1H), 8.20 (dd, J = 8.3, 1.6 Hz, 1H), 8.04 (dd, J = 1.7, 0.6 Hz, 1H), 7.96 7.90 (m, 2H), 7.82 (dd, J = 7.9, 1.7 Hz, 1H), 7.74 (dd, J = 7.3, 1.5 Hz, 1H), 7.66 (dd, J = 8.1, 7.4 Hz, 1H), 7.44 7.39 (m, 1H), 1.42 (s, 9H); Ms (ESI): m/z = 331.3 [M+H] +. 5-Methoxy-2-(quinolin-8-yl)isoindoline-1,3-dione (3d). White solid, 40 mg, 66% yield. (This compound is known [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.2, 1.7 Hz, 1H), 8.20 (dd, J = 8.3, 1.7 Hz, 1H), 7.93 (dd, J = 8.2, 1.4 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.74 (dd, J = 7.3, 1.5 Hz, 1H), 7.68 7.63 (m, 1H), 7.46 (d, J = 2.3 Hz, 1H), 7.41 (dd, J = 8.3, 4.2 Hz, 1H), 7.24 (dd, J = 8.3, 2.3 Hz, 1H), 3.94 (s, 3H); Ms (ESI): m/z = 305.3 [M+H] +. S14

5-Fluoro-2-(quinolin-8-yl)isoindoline-1,3-dione (3e). White solid, 43 mg, 74% yield. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.84 (dd, J = 4.2, 1.7 Hz, 1H), 8.20 (dd, J = 8.3, 1.6 Hz, 1H), 7.98 (dd, J = 8.2, 4.5 Hz, 1H), 7.95 (dd, J = 8.2, 1.4 Hz, 1H), 7.74 (dd, J = 7.3, 1.4 Hz, 1H), 7.68 7.63 (m, 2H), 7.48 7.40 (m, 2H); Ms (ESI): m/z = 293.5 [M+H] +. 5-Chloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3f). White solid, 38 mg, yield: 61%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.86 (dd, J = 4.2, 1.6 Hz, 1H), 8.26 (dd, J = 8.3, 1.4 Hz, 1H), 7.99 (dd, J = 8.2, 1.6 Hz, 2H), 7.94 (dd, J = 8.0, 0.5 Hz, 1H), 7.80 7.74 (m, 2H), 7.72 7.67 (m, 1H), 7.47 (dd, J = 8.4, 4.2 Hz, 1H); Ms (EI): m/z = 308 [M] +. 5-Bromo-2-(quinolin-8-yl)isoindoline-1,3-dione (3g). White solid, 47 mg, yield: 67%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.2, 1.6 Hz, 1H), 8.25 (dd, J = 8.3, 1.4 Hz, 1H), 8.14 (d, J = 1.7 Hz, 1H), 7.98 (dd, J = 8.2, 1.4 Hz, 1H), 7.95 (dd, J = 7.9, 1.7 Hz, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.75 (dd, J = 7.3, 1.4 Hz, 1H), 7.71 7.66 (m, 1H), 7.46 (dd, J = 8.3, 4.2 Hz, 1H); Ms (ESI): m/z = 353.2 [M+H] +. 2-(Quinolin-8-yl)-5-(trifluoromethyl)isoindoline-1,3-dione (3h). White solid, 43 mg, yield: 63%. S15

(This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.2, 1.6 Hz, 1H), 8.31 8.24 (m, 2H), 8.14 (d, J = 7.8 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 8.01 (dd, J = 8.2, 1.4 Hz, 1H), 7.78 (dd, J = 7.3, 1.5 Hz, 1H), 7.73 7.68 (m, 1H), 7.48 (dd, J = 8.3, 4.2 Hz, 1H); Ms (ESI): m/z = 343.5 [M+H] +. 5-Acetyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3i). White solid, 43 mg, yield: 68%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.84 (dd, J = 4.0, 1.3 Hz, 1H), 8.53 (s, 1H), 8.42 (dd, J = 7.8, 1.4 Hz, 1H), 8.24 (dd, J = 8.3, 1.3 Hz, 1H), 8.10 (d, J = 7.8 Hz, 1H), 7.99 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 7.2 Hz, 1H), 7.69 (t, J = 7.8 Hz, 1H), 7.46 (dd, J = 8.3, 4.1 Hz, 1H), 2.74 (s, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ 196.2, 167.1, 166.9, 151.0, 144.0, 141.9, 136.3, 135.6, 134.1, 132.9, 130.1, 129.9, 129.5, 129.3, 126.2, 124.2, 123.6, 122.0, 27.1; Ms (EI): m/z = 316 [M] + ; HRMS (EI): m/z [M] + Calcd for C 19 H 12 N 2 O 3, 316.0848; Found, 316.0847. 5-Nitro-2-(quinolin-8-yl)isoindoline-1,3-dione (3j). Yellow solid, 27 mg, yield: 42%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.86 8.80 (m, 2H), 8.70 (dd, J = 8.1, 1.7 Hz, 1H), 8.26 (dd, J = 8.3, 1.3 Hz, 1H), 8.20 (d, J = 8.1 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.78 (dd, J = 7.5, 1.0 Hz, 1H), 7.71 (t, J = 7.7 Hz, 1H), 7.48 (dd, J = 8.3, 4.2 Hz, 1H); Ms (ESI): m/z = 342.4 [M+Na] +. 1,3-Dioxo-2-(quinolin-8-yl)isoindoline-5-carbonitrile (3k). White solid, 13 mg, yield: 22%. S16

(This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.1, 1.5 Hz, 1H), 8.31 8.25 (m, 2H), 8.15 8.09 (m, 2H), 8.02 (dd, J = 8.1, 1.4 Hz, 1H), 7.77 (dd, J = 7.3, 1.5 Hz, 1H), 7.74 7.68 (m, 1H), 7.49 (dd, J = 8.4, 4.2 Hz, 1H); Ms (ESI): m/z = 300.4 [M+H] +. 4-Methyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3l). White solid, 41 mg, yield: 71%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.87 (dd, J = 4.2, 1.7 Hz, 1H), 8.22 (dd, J = 8.3, 1.7 Hz, 1H), 7.96 (dd, J = 8.2, 1.5 Hz, 1H), 7.83 (d, J = 7.4 Hz, 1H), 7.75 7.72 (m, 1H), 7.69 7.63 (m, 2H), 7.54 (d, J = 7.7 Hz, 1H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 2.76 (s, 3H); Ms (ESI): m/z = 289.4 [M+H] +. 4-Fluoro-2-(quinolin-8-yl)isoindoline-1,3-dione (3m). White solid, 39 mg, yield: 67%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.88 (dd, J = 4.2, 1.7 Hz, 1H), 8.23 (dd, J = 8.3, 1.7 Hz, 1H), 7.97 (dd, J = 8.2, 1.5 Hz, 1H), 7.82 7.76 (m, 2H), 7.74 (dd, J = 7.3, 1.5 Hz, 1H), 7.69 7.64 (m, 1H), 7.47 7.42 (m, 2H); Ms (ESI): m/z = 293.4 [M+H] +. Cl O N O N 4-Chloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3n). White solid, mp: 191-193 C, 41 mg, yield: 66%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.86 (dd, J = 4.2, 1.7 Hz, 1H), 8.23 (dd, J = 8.3, 1.7 Hz, 1H), 7.97 (dd, J = 8.2, 1.5 Hz, 1H), 7.91 (dt, J = 8.2, 4.1 Hz, 1H), 7.76 7.71 (m, 3H), 7.70 7.65 (m, 1H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H); 13 C NMR (126 MHz, CDCl 3 ) δ 166.5, 165.4, 151.0, 144.1, 136.2, 135.9, 135.0, 134.5, 131.9, 130.2, 129.8, 129.4, 129.3, 128.1, 126.1, 122.3, 121.9; Ms (EI): S17

m/z = 308 [M] + ; HRMS (EI): m/z [M] + Calcd for C 17 H 9 N 2 O 2 Cl, 308.0353; Found, 308.0353. Br O N O N 4-Bromo-2-(quinolin-8-yl)isoindoline-1,3-dione (3o). White solid, mp: 211-213 C, 42 mg, yield: 59%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.86 (dd, J = 4.2, 1.7 Hz, 1H), 8.24 (dd, J = 8.3, 1.7 Hz, 1H), 8.00 8.7.95 (m, 2H), 7.92 (dd, J = 8.1, 0.8 Hz, 1H), 7.75 (dd, J = 7.3, 1.5 Hz, 1H), 7.70 7.62 (m, 2H), 7.45 (dd, J = 8.3, 4.2 Hz, 1H); 13 C NMR (126 MHz, CDCl 3 ) δ 166.3, 165.8, 151.0, 144.1, 139.1, 136.3, 135.0, 134.6, 130.3, 129.9, 129.8, 129.4, 129.3, 126.1, 122.9, 122.0, 119.1; Ms (ESI): m/z = 353.0 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 17 H 10 BrN 2 O 2, 352.9920; Found, 352.9923. 2-(Quinolin-8-yl)-1H-benzo[e]isoindole-1,3(2H)-dione (3p). White solid, 44 mg, yield: 68%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 9.02 (d, J = 8.3 Hz, 1H), 8.86 (dd, J = 4.2, 1.5 Hz, 1H), 8.28 8.22 (m, 2H), 8.04 7.96 (m, 3H), 7.81 (dd, J = 7.2, 1.2 Hz, 1H), 7.77 7.67 (m, 3H), 7.45 (dd, J = 8.3, 4.1 Hz, 1H); Ms (ESI): m/z = 325.2 [M+H] +. 7-(Quinolin-8-yl)-6H-[1,3]dioxolo[4,5-e]isoindole-6,8(7H)-dione (3q). White solid, mp: 240-241 C, 31 mg, yield: 49%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.86 (dd, J = 4.2, 1.7 Hz, 1H), 8.22 (dd, J = 8.3, 1.7 Hz, 1H), 7.95 (dd, J = 8.2, 1.4 Hz, 1H), 7.73 (dd, J = 7.3, 1.5 Hz, 1H), 7.69 7.63 (m, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.43 (dd, J = 8.3, 4.2 Hz, 1H), 7.11 (d, J = 7.8 Hz, 1H), 6.28 (d, J = 3.1 Hz, 2H); 13 C NMR (126 MHz, CDCl 3 ) δ 167.0, 165.0, 154.3, 150.8, 144.2, 144.0, S18

136.3, 130.3, 129.7, 129.6, 129.3, 126.2, 125.7, 121.9, 119.4, 112.5, 112.1, 103.9; Ms (ESI): m/z = 319.2 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 18 H 11 N 2 O 4, 319.0713; Found, 319.0706. 4,6-Dimethyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3r). White solid, mp: 205-207 C, 43 mg, yield: 71%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.87 (dd, J = 4.1, 1.4 Hz, 1H), 8.22 (dd, J = 8.3, 1.3 Hz, 1H), 7.95 (dd, J = 8.1, 1.3 Hz, 1H), 7.73 (dd, J = 7.3, 1.3 Hz, 1H), 7.69 7.64 (m, 1H), 7.63 (s, 1H), 7.43 (dd, J = 8.3, 4.2 Hz, 1H), 7.34 (s, 1H), 2.71 (s, 3H), 2.50 (s, 3H); 13 C NMR (126 MHz, CDCl 3 ) δ 168.7, 168.2, 150.8, 144.9, 144.3, 138.3, 137.0, 136.3, 133.2, 130.4, 130.0, 129.4, 129.3, 126.6, 126.2, 122.2, 121.8, 21.8, 17.7; Ms (ESI): m/z = 303.2 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 19 H 15 N 2 O 2, 303.1128; Found, 303.1119. 4,6-Dichloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3s). White solid, mp: 233-235 C, 42 mg, yield: 61%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.85 (dd, J = 4.2, 1.7 Hz, 1H), 8.23 (dd, J = 8.3, 1.7 Hz, 1H), 7.98 (dd, J = 8.1, 1.5 Hz, 1H), 7.89 (d, J = 1.7 Hz, 1H), 7.75 7.71 (m, 2H), 7.69 7.65 (m, 1H), 7.45 (dd, J = 8.3, 4.2 Hz, 1H); 13 C NMR (126 MHz, CDCl 3 ) δ 165.3, 164.6, 151.0, 144.0, 141.2, 136.3, 135.5, 135.4, 132.7, 130.2, 129.9, 129.3, 129.2, 126.4, 126.1, 122.9, 122.0; Ms (EI): m/z = 342 [M] + ; HRMS (EI): m/z [M] + Calcd for C 17 H 8 N 2 O 2 Cl 2, 341.9963; Found, 341.9973. 4,7-Dimethyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3t). White solid, mp: 195-196 C, 47 mg, yield: 78%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.88 (dd, J = 4.2, 1.7 Hz, 1H), 8.22 (dd, J = 8.3, 1.5 Hz, 1H), 7.95 (dd, J = 8.1, 1.4 Hz, 1H), 7.72 (dd, J = 7.3, 1.5 Hz, 1H), 7.69 7.64 (m, 1H), 7.43 (dd, J S19

= 8.3, 4.2 Hz, 1H), 7.40 (s, 2H), 2.71 (s, 6H); 13 C NMR (126 MHz, CDCl 3 ) δ 168.7, 150.9, 144.5, 136.3, 135.9, 130.4, 130.0, 129.4, 129.3, 129.3, 126.1, 121.8, 17.5; Ms (ESI): m/z = 303.3 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 19 H 15 N 2 O 2, 303.1128; Found, 303.1129. 3-Phenyl-1-(quinolin-8-yl)-1H-pyrrole-2,5-dione (3u). Pale yellow oil, 22 mg, yield: 37%. (This compound is known. [4] ) 1 H NMR (400 MHz, CDCl 3 ) δ 8.88 (dd, J = 4.1, 1.6 Hz, 1H), 8.22 (dd, J = 8.3, 1.6 Hz, 1H), 8.07 8.00 (m, 2H), 7.94 (dd, J = 8.1, 1.4 Hz, 1H), 7.73 (dd, J = 7.3, 1.5 Hz, 1H), 7.68 7.62 (m, 1H), 7.52 7.47 (m, 3H), 7.44 (dd, J = 8.3, 4.2 Hz, 1H), 7.00 (s, 1H); Ms (ESI): m/z = 301.3 [M+H] +. 3,4-Diphenyl-1-(quinolin-8-yl)-1H-pyrrole-2,5-dione (3v). Pale yellow solid, mp: 205-207 C, 59 mg, yield: 78%. 1 H NMR (400 MHz, CDCl 3 ) δ 8.92 (dd, J = 4.2, 1.6 Hz, 1H), 8.23 (dd, J = 8.3, 1.5 Hz, 1H), 7.95 (dd, J = 8.2, 1.4 Hz, 1H), 7.77 (dd, J = 7.3, 1.4 Hz, 1H), 7.69 7.64 (m, 1H), 7.63 7.58 (m, 4H), 7.46 (dd, J = 8.3, 4.2 Hz, 1H), 7.41 7.35 (m, 6H); 13 C NMR (126 MHz, CDCl 3 ) δ 170.1, 150.8, 144.3, 136.7, 136.3, 130.3, 130.2, 129.9, 129.8, 129.4, 129.3, 128.8, 128.5, 126.2, 121.9; Ms (ESI): m/z = 377.2 [M+H] + ; HRMS (ESI): m/z [M+H] + Calcd for C 25 H 17 N 2 O 2, 377.1285; Found, 377.1278. 2-(Quinolin-8-yl)-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione (3w). White solid, mp: 175-177 C, S20

19 mg, yield: 35%. 1 H NMR (400 MHz, CDCl 3 ) δ 9.31 (d, J = 1.1 Hz, 1H), 9.16 (d, J = 4.8 Hz, 1H), 8.85 (dd, J = 4.2, 1.7 Hz, 1H), 8.25 (dd, J = 8.3, 1.7 Hz, 1H), 8.00 (dd, J = 8.2, 1.5 Hz, 1H), 7.91 (dd, J = 4.8, 1.1 Hz, 1H), 7.76 (dd, J = 7.3, 1.5 Hz, 1H), 7.72 7.67 (m, 1H), 7.47 (dd, J = 8.3, 4.2 Hz, 1H); 13 C NMR (126 MHz, CDCl 3 ) δ 166.7, 166.4, 155.7, 151.0, 145.4, 143.9, 139.8, 136.3, 130.1, 130.0, 129.3, 129.1, 126.3, 126.1, 122.1, 117.3; Ms (EI): m/z = 275 [M] + ; HRMS (EI): m/z [M] + Calcd for C 16 H 9 N 3 O 2, 275.0695; Found, 275.0698. 15. References [1] (a) Grigorjeva, L.; Daugulis, O. Org. Lett. 2014, 16, 4684. (b) Grigorjeva, L.; Daugulis, O. Angew. Chem., Int. Ed. 2014, 53, 10209. (c) Gandeepan, P.; Rajamalli, P.; Cheng, C.-H. Angew. Chem., Int. Ed. 2016, 55, 4308. [2] Chilwal, A.; Deep, G.; Malhotra, P.; Narula, A. K. J. Coord. Chem. 2013, 66, 1046. [3] (a) Feigl, F.; Anger, V. Spot Tests in Inorganic Analysis 6th editions; Elsevier, pp. 169. (b) Wang, L.; Ren, X.; Yu, J.; Jiang, Y.; Cheng, J. J. Org. Chem. 2013, 78, 12076. [4] (a) Wu, X.; Zhao, Y.; Ge, H. J. Am. Chem. Soc. 2015, 137, 4924. (b) Wu, X.; Miao, J.; Li, Y.; Li, G.; Ge, H. Chem. Sci. 2016, 7, 5260. (c) Grigorjeva, L.; Daugulis, Org. Lett. 2014, 16, 4688. S21

16. Copies of NMR Spectra Data 3,5-dichloro-N-(quinolin-8-yl)benzamide (1s) S22

3,5-dichloro-N-(quinolin-8-yl)benzamide (1s) S23

Isopropyl 2-(quinolin-8-ylcarbamoyl)benzoate (4) S24

Isopropyl 2-(quinolin-8-ylcarbamoyl)benzoate (4) S25

2-(quinolin-8-yl)isoindoline-1,3-dione (3a) S26

5-methyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3b) S27

5-(tert-butyl)-2-(quinolin-8-yl)isoindoline-1,3-dione (3c) S28

5-methoxy-2-(quinolin-8-yl)isoindoline-1,3-dione (3d) S29

5-fluoro-2-(quinolin-8-yl)isoindoline-1,3-dione (3e) S30

5-chloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3f) S31

5-bromo-2-(quinolin-8-yl)isoindoline-1,3-dione (3g) S32

2-(quinolin-8-yl)-5-(trifluoromethyl)isoindoline-1,3-dione (3h) S33

5-acetyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3i) S34

5-acetyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3i) S35

5-nitro-2-(quinolin-8-yl)isoindoline-1,3-dione (3j) S36

1,3-dioxo-2-(quinolin-8-yl)isoindoline-5-carbonitrile (3k) S37

4-methyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3l) S38

4-fluoro-2-(quinolin-8-yl)isoindoline-1,3-dione (3m) S39

4-chloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3n) S40

4-chloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3n) S41

4-bromo-2-(quinolin-8-yl)isoindoline-1,3-dione (3o) S42

4-bromo-2-(quinolin-8-yl)isoindoline-1,3-dione (3o) S43

2-(quinolin-8-yl)-1H-benzo[e]isoindole-1,3(2H)-dione (3p) S44

7-(quinolin-8-yl)-6H-[1,3]dioxolo[4,5-e]isoindole-6,8(7H)-dione (3q) S45

7-(quinolin-8-yl)-6H-[1,3]dioxolo[4,5-e]isoindole-6,8(7H)-dione (3q) S46

4,6-dimethyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3r) S47

4,6-dimethyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3r) S48

4,6-dichloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3s) S49

4,6-dichloro-2-(quinolin-8-yl)isoindoline-1,3-dione (3s) S50

4,7-dimethyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3t) S51

4,7-dimethyl-2-(quinolin-8-yl)isoindoline-1,3-dione (3t) S52

3-phenyl-1-(quinolin-8-yl)-1H-pyrrole-2,5-dione (3u) S53

3,4-diphenyl-1-(quinolin-8-yl)-1H-pyrrole-2,5-dione (3v) S54

3,4-diphenyl-1-(quinolin-8-yl)-1H-pyrrole-2,5-dione (3v) S55

2-(quinolin-8-yl)-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione (3w) S56

2-(quinolin-8-yl)-1H-pyrrolo[3,4-c]pyridine-1,3(2H)-dione (3w) S57